1 00:00:00,030 --> 00:00:02,410 The following content is provided under a Creative 2 00:00:02,410 --> 00:00:03,830 Commons license. 3 00:00:03,830 --> 00:00:06,840 Your support will help MIT OpenCourseWare continue to 4 00:00:06,840 --> 00:00:10,530 offer high-quality educational resources for free. 5 00:00:10,530 --> 00:00:13,400 To make a donation, or view additional materials from 6 00:00:13,400 --> 00:00:17,490 hundreds of MIT courses, visit MIT OpenCourseWare at 7 00:00:17,490 --> 00:00:18,740 ocw.mit.edu. 8 00:00:21,570 --> 00:00:21,860 PROFESSOR: All right. 9 00:00:21,860 --> 00:00:27,000 So here's the box score from the celebration on Monday. 10 00:00:27,000 --> 00:00:29,012 Class average improved considerably. 11 00:00:29,012 --> 00:00:32,530 A number of people moved from the sad face 12 00:00:32,530 --> 00:00:35,060 to the smiley face. 13 00:00:35,060 --> 00:00:38,630 I would still tell anybody who is down over here that the 14 00:00:38,630 --> 00:00:44,850 final exam is coming, and if you perform well on the final 15 00:00:44,850 --> 00:00:46,670 exam, we'll take a look at the overall 16 00:00:46,670 --> 00:00:47,920 performance of the semester. 17 00:00:47,920 --> 00:00:53,020 So get in and talk to us, if you want to, to see what we 18 00:00:53,020 --> 00:00:57,300 can do to help you succeed here. 19 00:00:57,300 --> 00:01:01,790 But it takes a little bit of effort on your part as well. 20 00:01:01,790 --> 00:01:02,980 I think that's all I want to say. 21 00:01:02,980 --> 00:01:06,620 There will be a weekly test, a weekly minor celebration on 22 00:01:06,620 --> 00:01:08,210 Tuesday, as normal. 23 00:01:08,210 --> 00:01:11,280 So today we're going to start the last of two units. 24 00:01:11,280 --> 00:01:14,030 We have two units left before the end of the semester. 25 00:01:14,030 --> 00:01:16,860 And this one is biochemistry. 26 00:01:16,860 --> 00:01:21,310 And it's one of these integrative topics that's 27 00:01:21,310 --> 00:01:23,280 going to bring together a lot of the material that we've 28 00:01:23,280 --> 00:01:25,850 looked at in the past. 29 00:01:25,850 --> 00:01:29,690 And biochemistry overview, it's the chemistry of living 30 00:01:29,690 --> 00:01:33,740 organisms. And the first thing to point out is that 31 00:01:33,740 --> 00:01:37,630 biochemistry is governed by the same laws that apply to 32 00:01:37,630 --> 00:01:38,720 inanimate matter. 33 00:01:38,720 --> 00:01:41,290 And apropos of that, I'd like to read something that was 34 00:01:41,290 --> 00:01:46,500 written by the Nobel Prize winner, Richard Feynman. 35 00:01:46,500 --> 00:01:49,590 "If in some cataclysm, all of scientific knowledge were to 36 00:01:49,590 --> 00:01:54,260 be destroyed, and only one sentence passed on to the next 37 00:01:54,260 --> 00:01:57,960 generations of creatures, what statement would contain the 38 00:01:57,960 --> 00:02:01,860 most information in the fewest words? 39 00:02:01,860 --> 00:02:05,900 I believe that it is the atomic hypothesis, or the 40 00:02:05,900 --> 00:02:09,300 atomic factor, whatever you wish to call it, that all 41 00:02:09,300 --> 00:02:13,290 things are made of atoms. Little particles that move 42 00:02:13,290 --> 00:02:16,780 around in perpetual motion, attracting each other when 43 00:02:16,780 --> 00:02:20,450 they are a little distance apart, but repelling upon 44 00:02:20,450 --> 00:02:22,680 being squeezed into one another." 45 00:02:22,680 --> 00:02:26,670 So that's the first thing to point out. 46 00:02:26,670 --> 00:02:29,030 That it's the same chemistry that we've been 47 00:02:29,030 --> 00:02:30,250 learning up until now. 48 00:02:30,250 --> 00:02:33,910 And in fact, I think I've got a a slide that captures the-- 49 00:02:33,910 --> 00:02:36,920 there's the Feynman quote, the last part of it. 50 00:02:36,920 --> 00:02:39,940 Second thing is, by way of introduction, you see a boom 51 00:02:39,940 --> 00:02:42,090 around us today in biotech. 52 00:02:42,090 --> 00:02:43,800 And what is the biotech? 53 00:02:43,800 --> 00:02:46,750 It's the molecular biology, it's the commercialization of 54 00:02:46,750 --> 00:02:47,950 molecular biology. 55 00:02:47,950 --> 00:02:52,220 Biology, when I was your age, was classification, taxonomy, 56 00:02:52,220 --> 00:02:56,160 naming things and figuring out what bin they fit into. 57 00:02:56,160 --> 00:02:57,770 Today it's not that. 58 00:02:57,770 --> 00:02:59,250 It's molecular biology. 59 00:02:59,250 --> 00:03:00,820 Well, what's the molecular science? 60 00:03:00,820 --> 00:03:03,940 Molecular science is chemistry, and it's solid 61 00:03:03,940 --> 00:03:04,870 state chemistry. 62 00:03:04,870 --> 00:03:07,110 Biology is solid state chemistry. 63 00:03:07,110 --> 00:03:11,610 We are solid state devices made of soft matter with an 64 00:03:11,610 --> 00:03:13,830 endoskeleton that's ceramic, and so on. 65 00:03:13,830 --> 00:03:16,610 But we are solid state devices. 66 00:03:16,610 --> 00:03:18,710 So this is solid state chemistry and material 67 00:03:18,710 --> 00:03:23,210 science, and that's why we talk about it in 3.091. 68 00:03:23,210 --> 00:03:25,870 And why now? 69 00:03:25,870 --> 00:03:29,060 Why is the biochem revolution only now? 70 00:03:29,060 --> 00:03:31,140 Well, it has to do with complexity. 71 00:03:31,140 --> 00:03:34,170 You can think about complexity from the standpoint of 72 00:03:34,170 --> 00:03:39,690 materials, and in fact, lay out the ages of man. 73 00:03:39,690 --> 00:03:40,880 The Stone Age. 74 00:03:40,880 --> 00:03:43,520 The Stone Age precedes the Bronze Age. 75 00:03:43,520 --> 00:03:44,270 Why? 76 00:03:44,270 --> 00:03:47,170 Because stone is found in nature naturally. 77 00:03:47,170 --> 00:03:51,070 To use stone requires only to cut it and change its shape. 78 00:03:51,070 --> 00:03:53,700 But you make bronze, you have to engage in chemical 79 00:03:53,700 --> 00:03:54,890 processing. 80 00:03:54,890 --> 00:03:57,550 There's a chemical conversion that requires a higher level 81 00:03:57,550 --> 00:03:59,990 of societal sophistication. 82 00:03:59,990 --> 00:04:01,690 And then iron follows bronze. 83 00:04:01,690 --> 00:04:01,990 Why? 84 00:04:01,990 --> 00:04:04,720 Because iron melts at a higher temperature, so you have to 85 00:04:04,720 --> 00:04:07,310 have a higher level of technology in order to make 86 00:04:07,310 --> 00:04:10,840 the furnaces and to conduct the reduction reaction to 87 00:04:10,840 --> 00:04:12,600 extract iron. 88 00:04:12,600 --> 00:04:14,390 And then comes polymers. 89 00:04:14,390 --> 00:04:18,240 Polymers, the birth of synthetics, come when? 90 00:04:18,240 --> 00:04:22,650 First polymers were around, what, 1829, when the 91 00:04:22,650 --> 00:04:24,960 pharmacist was playing with the styrene. 92 00:04:24,960 --> 00:04:28,350 And then it explodes in the 20th century. 93 00:04:28,350 --> 00:04:30,900 And then mid-century we get silicon. 94 00:04:30,900 --> 00:04:33,360 And silicon is even more sophisticated, because we had 95 00:04:33,360 --> 00:04:35,220 to understand quantum mechanics to even understand 96 00:04:35,220 --> 00:04:36,470 that we needed silicon. 97 00:04:39,160 --> 00:04:44,080 We could convert beach sand into silicon back in 1500, but 98 00:04:44,080 --> 00:04:48,140 who knew what to do with silicon in 1500? 99 00:04:48,140 --> 00:04:51,510 And then finally comes the end of the 20th century, and now 100 00:04:51,510 --> 00:04:53,200 we're dealing with this stuff. 101 00:04:53,200 --> 00:04:58,930 So that sort of puts things in perspective. 102 00:04:58,930 --> 00:05:02,290 So what we're going to do today is start the treatment 103 00:05:02,290 --> 00:05:03,480 of biomolecules. 104 00:05:03,480 --> 00:05:05,110 And the first thing I want to say, is we're going to be 105 00:05:05,110 --> 00:05:09,080 talking about macromolecules but not polymers. 106 00:05:09,080 --> 00:05:11,690 So all polymers are macromolecules, but all 107 00:05:11,690 --> 00:05:13,790 macromolecules are not polymers. 108 00:05:13,790 --> 00:05:14,910 What's the difference? 109 00:05:14,910 --> 00:05:19,910 In polymers, we have a common repeat unit, whereas in the 110 00:05:19,910 --> 00:05:22,250 life sciences, Mother Nature is a polymer 111 00:05:22,250 --> 00:05:24,110 engineer gone wild. 112 00:05:24,110 --> 00:05:29,160 She takes different functional groups and puts them at every 113 00:05:29,160 --> 00:05:32,850 stage along the way, as opposed to polyethylene, where 114 00:05:32,850 --> 00:05:35,990 it is the same functional group at every stop. 115 00:05:35,990 --> 00:05:39,600 So it is exploded polymer chemistry, 116 00:05:39,600 --> 00:05:41,170 macromolecular chemistry. 117 00:05:41,170 --> 00:05:44,560 So there's four classifications of 118 00:05:44,560 --> 00:05:45,430 biomolecules. 119 00:05:45,430 --> 00:05:48,790 The proteins, carbohydrates, lipids, nucleic acids. 120 00:05:48,790 --> 00:05:50,370 And we're going to look at three of the four. 121 00:05:50,370 --> 00:05:52,180 We'll start today with proteins. 122 00:05:52,180 --> 00:05:55,450 We will study lipids and nucleic acids, but in the time 123 00:05:55,450 --> 00:05:57,200 allowed, we're going to lose the sugars. 124 00:05:57,200 --> 00:06:01,330 So you'll take 7.012 or something to satisfy the 125 00:06:01,330 --> 00:06:03,980 Institute biology requirement, you'll go much 126 00:06:03,980 --> 00:06:05,110 more deeply into it. 127 00:06:05,110 --> 00:06:07,850 But I think you're going to have very good preparation 128 00:06:07,850 --> 00:06:12,170 after three lectures here, and you'll be able to put together 129 00:06:12,170 --> 00:06:14,870 a lot of the material that we've looked at prior. 130 00:06:14,870 --> 00:06:17,220 So the first thing we're going to look at is proteins. 131 00:06:17,220 --> 00:06:20,290 Proteins are macromolecules, and they're formed by 132 00:06:20,290 --> 00:06:24,600 polymerization of monomers known as amino acids. 133 00:06:24,600 --> 00:06:28,760 So before we can talk about proteins, we're going to first 134 00:06:28,760 --> 00:06:31,230 look at amino acids. 135 00:06:31,230 --> 00:06:33,140 So let's do that. 136 00:06:33,140 --> 00:06:38,020 And amino acids are substances that have the following 137 00:06:38,020 --> 00:06:39,120 skeletal structure. 138 00:06:39,120 --> 00:06:40,970 I'm going to start a new board for this. 139 00:06:40,970 --> 00:06:44,330 So this is the basic skeletal structure of the amino acid. 140 00:06:44,330 --> 00:06:47,790 It's got a central carbon, sp3 hybridized with 141 00:06:47,790 --> 00:06:49,580 four struts on it. 142 00:06:49,580 --> 00:06:52,830 Down in the lower left corner, we have the amino group, which 143 00:06:52,830 --> 00:06:55,006 is nitrogen and two hydrogens. 144 00:06:59,990 --> 00:07:02,400 So there's one, two, three bonds off the nitrogen, and I 145 00:07:02,400 --> 00:07:06,380 want to emphasize but it's still got this unpaired set of 146 00:07:06,380 --> 00:07:10,630 electrons, which we know makes this thing a Bronsted base. 147 00:07:10,630 --> 00:07:13,040 And it's going to have a site here for proton attachment. 148 00:07:13,040 --> 00:07:15,650 And that's a big feature here in amino acids. 149 00:07:15,650 --> 00:07:18,450 So this is the amino group. 150 00:07:21,940 --> 00:07:25,195 And it acts as a Bronsted base. 151 00:07:28,890 --> 00:07:31,140 So it's a proton attachment site. 152 00:07:31,140 --> 00:07:36,090 Second strut is hydrogen in every amino acid. 153 00:07:36,090 --> 00:07:39,410 The third site, over here, is the carboxylic acid end, and 154 00:07:39,410 --> 00:07:43,830 that's carbon with a double bond, and one, two, three, 155 00:07:43,830 --> 00:07:44,710 four, all right? 156 00:07:44,710 --> 00:07:46,840 Every carbon needs four struts, and the 157 00:07:46,840 --> 00:07:48,600 fourth one has the OH. 158 00:07:48,600 --> 00:07:51,530 And this is the H that can fall off. 159 00:07:51,530 --> 00:07:53,720 So this is the proton donor here. 160 00:07:53,720 --> 00:08:01,580 This is carboxylic acid end. 161 00:08:01,580 --> 00:08:06,490 So this is three of the four ends of the carbon bonds are 162 00:08:06,490 --> 00:08:08,400 fixed in all amino acids. 163 00:08:08,400 --> 00:08:11,990 And then the fourth one is free to be specified. 164 00:08:11,990 --> 00:08:13,160 This is all R. 165 00:08:13,160 --> 00:08:14,950 R is a placeholder. 166 00:08:14,950 --> 00:08:16,320 It stands for the substituent. 167 00:08:19,840 --> 00:08:21,200 This is the substituent. 168 00:08:21,200 --> 00:08:22,450 And this is nature's choice. 169 00:08:26,290 --> 00:08:28,350 So you can put anything here. 170 00:08:28,350 --> 00:08:30,560 There are hundreds of amino acids. 171 00:08:30,560 --> 00:08:33,480 There are only 20 seen in protein. 172 00:08:33,480 --> 00:08:36,120 But anything that goes up here, with this structure, is 173 00:08:36,120 --> 00:08:36,890 an amino acid. 174 00:08:36,890 --> 00:08:36,970 I don't care. 175 00:08:36,970 --> 00:08:39,120 You could put a cyanide up here, for all I care. 176 00:08:39,120 --> 00:08:42,740 It'll still qualify as a amino acid if these other three 177 00:08:42,740 --> 00:08:44,610 sites are filled in the following matter. 178 00:08:44,610 --> 00:08:53,160 So 20 seen in amino acids. 179 00:08:53,160 --> 00:08:55,000 20 of those in amino acids. 180 00:08:55,000 --> 00:08:58,340 And now I want to look at the substituents and break those 181 00:08:58,340 --> 00:08:59,940 into categories. 182 00:08:59,940 --> 00:09:02,900 So there's four categories of substituents. 183 00:09:02,900 --> 00:09:06,150 In other words, the 20 here can be broken into four 184 00:09:06,150 --> 00:09:07,400 categories. 185 00:09:09,140 --> 00:09:11,150 Four categories of R. 186 00:09:11,150 --> 00:09:14,000 And we can group those by their chemical properties. 187 00:09:14,000 --> 00:09:19,850 The first group, I took this from one of the other texts. 188 00:09:19,850 --> 00:09:21,210 Yeah, this is from one of the other texts. 189 00:09:21,210 --> 00:09:23,210 So there's the 20 amino acids. 190 00:09:23,210 --> 00:09:26,030 So I'm now highlighting some of the ones that are nonpolar. 191 00:09:29,370 --> 00:09:30,440 So what do you see there? 192 00:09:30,440 --> 00:09:34,080 The nonpolar ones, you see for R. 193 00:09:34,080 --> 00:09:36,140 The R group is above here. 194 00:09:36,140 --> 00:09:36,350 so? 195 00:09:36,350 --> 00:09:39,790 This is just plain hydrogen, which is nonpolar There's a 196 00:09:39,790 --> 00:09:42,410 methyl group, CH3, so that's alanine. 197 00:09:42,410 --> 00:09:47,770 Here's a methylene with two methyls, so this is alanine, 198 00:09:47,770 --> 00:09:49,300 and so on and so forth. 199 00:09:49,300 --> 00:09:53,250 So the different groups hang off that R 200 00:09:53,250 --> 00:09:55,610 position at the top. 201 00:09:55,610 --> 00:10:00,450 So these are nonpolar, and this also is characterized by 202 00:10:00,450 --> 00:10:01,480 being hydrophobic. 203 00:10:01,480 --> 00:10:04,490 So that end becomes hydrophobic when we use 204 00:10:04,490 --> 00:10:05,990 nonpolar group. 205 00:10:05,990 --> 00:10:12,140 The second option is to have polar substituents. 206 00:10:12,140 --> 00:10:15,505 And some of them even have hydrogen bonding capability. 207 00:10:21,330 --> 00:10:22,680 That's the second category. 208 00:10:22,680 --> 00:10:24,740 And of course those are going to be hydrophilic. 209 00:10:30,270 --> 00:10:34,650 The third group is charged. 210 00:10:34,650 --> 00:10:42,350 The third group actually has a charge end, which becomes a 211 00:10:42,350 --> 00:10:44,120 negative ion in aqueous solution. 212 00:10:49,440 --> 00:10:53,210 And these are going to be strongly hydrophilic. 213 00:11:00,480 --> 00:11:02,360 And also-- 214 00:11:02,360 --> 00:11:03,610 [BREAK IN VIDEO] 215 00:11:14,010 --> 00:11:17,900 PROFESSOR: Number nine, number nine, number nine. 216 00:11:17,900 --> 00:11:19,310 Can you hear? 217 00:11:19,310 --> 00:11:19,930 Yes? 218 00:11:19,930 --> 00:11:20,620 Yeah, that's good. 219 00:11:20,620 --> 00:11:22,505 Hydrophilic and acidic. 220 00:11:25,100 --> 00:11:27,600 The acoustics here today are very different, huh? 221 00:11:27,600 --> 00:11:31,290 We're missing a few bodies. 222 00:11:31,290 --> 00:11:33,960 We need to put the crash test dummies in here, and then 223 00:11:33,960 --> 00:11:36,030 we'll have the same acoustic sound. 224 00:11:36,030 --> 00:11:36,370 All right. 225 00:11:36,370 --> 00:11:41,840 And then the fourth category gives you a cation, R plus, in 226 00:11:41,840 --> 00:11:44,390 aqueous solution, which then, strongly 227 00:11:44,390 --> 00:11:48,540 hydrophilic and basic. 228 00:11:48,540 --> 00:11:49,350 So we'll go through. 229 00:11:49,350 --> 00:11:54,250 Now, our bodies can synthesize only 10 of the 20 amino acids, 230 00:11:54,250 --> 00:11:56,740 and then the other 10 we have to get from diets. 231 00:11:56,740 --> 00:11:58,770 So when you look at some of these fad diets, you might 232 00:11:58,770 --> 00:12:01,700 want to check and make sure you're getting all of the 233 00:12:01,700 --> 00:12:03,080 proper nutrients. 234 00:12:03,080 --> 00:12:07,530 Now another of the structural features of amino acids that's 235 00:12:07,530 --> 00:12:10,570 important is chirality. 236 00:12:10,570 --> 00:12:13,520 Chirality is a feature of amino acids. 237 00:12:13,520 --> 00:12:15,320 And what is chirality? 238 00:12:15,320 --> 00:12:17,680 I'll show you by way of example. 239 00:12:17,680 --> 00:12:20,220 Chirality talks about handedness. 240 00:12:23,990 --> 00:12:25,750 Comes from the Greek word for glove. 241 00:12:25,750 --> 00:12:31,210 So let me show you molecules that have the chirality that 242 00:12:31,210 --> 00:12:32,730 distinguishes them. 243 00:12:32,730 --> 00:12:37,070 So I'm going to give an example with alanine. 244 00:12:37,070 --> 00:12:41,020 With alanine, the R-substituent group is equal 245 00:12:41,020 --> 00:12:42,910 to the methyl, CH3. 246 00:12:42,910 --> 00:12:47,250 So I'm going to put CH3 up here for the substituent, and 247 00:12:47,250 --> 00:12:50,550 then the other three stations are as we know them to be. 248 00:12:50,550 --> 00:12:53,520 So there's the amino group, there's the hydrogen, and 249 00:12:53,520 --> 00:12:55,370 here's the carboxylic acid. 250 00:12:55,370 --> 00:12:58,210 And note, look at the compact notation here. 251 00:12:58,210 --> 00:13:00,110 We write COOH. 252 00:13:00,110 --> 00:13:03,300 This O is not bonded to the O next to it. 253 00:13:03,300 --> 00:13:06,230 Both O's are bonded to the carbon, but this 254 00:13:06,230 --> 00:13:08,110 is compressed notation. 255 00:13:08,110 --> 00:13:09,420 COOH, and then this. 256 00:13:09,420 --> 00:13:14,060 So this is alanine, and I could just as easily write the 257 00:13:14,060 --> 00:13:16,240 molecule in the following manner. 258 00:13:16,240 --> 00:13:19,110 I would still satisfy the requirement that I have an 259 00:13:19,110 --> 00:13:24,810 amino group, a hydrogen group, a carboxylic acid group. 260 00:13:24,810 --> 00:13:27,800 Actually, if I want to get really fancy in chemistry, I 261 00:13:27,800 --> 00:13:28,650 could write it this way. 262 00:13:28,650 --> 00:13:32,760 COOH, and everybody knows H can't bond to two species. 263 00:13:32,760 --> 00:13:34,130 In fact, it's the carbon here. 264 00:13:34,130 --> 00:13:35,130 But it's OK. 265 00:13:35,130 --> 00:13:37,940 It's compressed and in the methyl group up here. 266 00:13:37,940 --> 00:13:42,000 And what you notice is that the molecule on the left is 267 00:13:42,000 --> 00:13:44,800 distinguishable from the molecule on the right. 268 00:13:44,800 --> 00:13:47,860 These are not the same molecule, even though the same 269 00:13:47,860 --> 00:13:51,850 substituents are here, and the other features are preserved. 270 00:13:51,850 --> 00:13:54,610 This cannot be superimposed. 271 00:13:54,610 --> 00:13:55,940 So you could distinguish these two. 272 00:13:55,940 --> 00:13:58,000 If I just threw them on the floor, you'd be able to pick 273 00:13:58,000 --> 00:14:00,950 them up and say, one has the amino group in this 274 00:14:00,950 --> 00:14:04,890 orientation, and if I put the other one, with the methyl 275 00:14:04,890 --> 00:14:07,790 above and the hydrogen below, I will have the amino group on 276 00:14:07,790 --> 00:14:09,090 the other side. 277 00:14:09,090 --> 00:14:13,990 And these things also are optically active. 278 00:14:13,990 --> 00:14:16,650 And through their optical activity, we 279 00:14:16,650 --> 00:14:18,690 give them their names. 280 00:14:18,690 --> 00:14:20,620 And so let's take a look here. 281 00:14:20,620 --> 00:14:21,250 All right. 282 00:14:21,250 --> 00:14:24,050 This is just a little bit more of the amino acids. 283 00:14:24,050 --> 00:14:27,070 And actually, one of our former 3.091 TAs, Andrew 284 00:14:27,070 --> 00:14:30,740 Magyar, who just defended his PhD thesis. 285 00:14:30,740 --> 00:14:34,100 I was on his committee, and he did a splendid job, and used 286 00:14:34,100 --> 00:14:38,000 his 3.091 principles to get through his advanced biology. 287 00:14:38,000 --> 00:14:41,300 This is a list which is going to be part of the PDF that 288 00:14:41,300 --> 00:14:44,380 I'll post. But there are 20 amino acids, and as you know, 289 00:14:44,380 --> 00:14:47,750 there are 26 letters in the alphabet we use in English. 290 00:14:47,750 --> 00:14:50,520 And so if you want to write them in compressed form, you 291 00:14:50,520 --> 00:14:52,250 just use one of these letters. 292 00:14:52,250 --> 00:14:54,190 There's the three-letter notation as 293 00:14:54,190 --> 00:14:56,250 well, so ALA is alanine. 294 00:14:56,250 --> 00:15:00,230 And in the past, I used to have contests in 3.091 to ask 295 00:15:00,230 --> 00:15:03,190 students to give me the airports, if these were 296 00:15:03,190 --> 00:15:04,570 three-letter airport codes. 297 00:15:04,570 --> 00:15:06,300 You see, it always comes around Thanksgiving, and 298 00:15:06,300 --> 00:15:07,660 people are busy heading to-- 299 00:15:07,660 --> 00:15:10,950 and it turns out that 19 of the 20 amino acids have 300 00:15:10,950 --> 00:15:15,240 airport codes that correspond to the amino acid three-letter 301 00:15:15,240 --> 00:15:19,720 abbreviations, with the exception of glutamine, GLN. 302 00:15:19,720 --> 00:15:23,750 There's no airport that has GLN as its thing. 303 00:15:23,750 --> 00:15:26,890 That's a piece of trivia that will get you the last wedge in 304 00:15:26,890 --> 00:15:27,710 Trivial Pursuit. 305 00:15:27,710 --> 00:15:29,970 And then this is the one-letter abbreviation. 306 00:15:29,970 --> 00:15:32,100 So Andrew has put them in this form. 307 00:15:32,100 --> 00:15:35,690 So there again, I have the basic, the acidic, the 308 00:15:35,690 --> 00:15:38,550 aliphatic are the ones that are nonpolar. 309 00:15:38,550 --> 00:15:40,260 And this is another way to look at it. 310 00:15:40,260 --> 00:15:43,290 And here's the base structure, and here's the whole thing in 311 00:15:43,290 --> 00:15:44,540 monochrome. 312 00:15:44,540 --> 00:15:44,900 All right. 313 00:15:44,900 --> 00:15:46,030 So that's part of the thing. 314 00:15:46,030 --> 00:15:46,260 OK. 315 00:15:46,260 --> 00:15:47,760 So here's what I'm talking about. 316 00:15:47,760 --> 00:15:49,040 The mirror plane. 317 00:15:49,040 --> 00:15:53,250 So this box can be mirrored as shown. 318 00:15:53,250 --> 00:15:55,310 But as soon as you put a distinguishing mark in the 319 00:15:55,310 --> 00:15:59,220 lower right-hand corner here, the box on the left is not 320 00:15:59,220 --> 00:16:01,730 superimposable to the box on the right. 321 00:16:01,730 --> 00:16:03,610 They are distinguishable. 322 00:16:03,610 --> 00:16:06,350 And so these things will have different chemical 323 00:16:06,350 --> 00:16:10,440 reactivities, not melting point boiling point, but how 324 00:16:10,440 --> 00:16:11,880 they react with other molecules. 325 00:16:14,380 --> 00:16:15,460 So here's the chirologics. 326 00:16:15,460 --> 00:16:17,110 Your gloves are chiral. 327 00:16:17,110 --> 00:16:19,590 If you try to put your right-handed glove on your 328 00:16:19,590 --> 00:16:22,570 left hand, it's a poor fit, whereas the 329 00:16:22,570 --> 00:16:26,800 flask here is achiral. 330 00:16:26,800 --> 00:16:28,840 And now here are some molecules, just to show you 331 00:16:28,840 --> 00:16:30,300 how this translates into chemistry. 332 00:16:30,300 --> 00:16:34,500 So this molecule is chiral, this molecule is not chiral. 333 00:16:34,500 --> 00:16:38,310 And it has to do with the number of positions that are 334 00:16:38,310 --> 00:16:39,560 distinguishable. 335 00:16:42,390 --> 00:16:44,880 And how does this fit into the grand scheme of things? 336 00:16:44,880 --> 00:16:47,660 It's sort of a form of stereoisomerism, isn't it? 337 00:16:47,660 --> 00:16:52,140 Remember, we looked at the geometric isomers. 338 00:16:52,140 --> 00:16:53,440 Here's an example. 339 00:16:53,440 --> 00:16:54,730 This is dichloroethylene. 340 00:16:54,730 --> 00:16:58,890 We looked at butene. 341 00:16:58,890 --> 00:17:01,030 But here we've got cis-isomer, here we've got the 342 00:17:01,030 --> 00:17:03,750 trans-isomer, where the chlorines are on opposite 343 00:17:03,750 --> 00:17:04,990 sides of the double bond here. 344 00:17:04,990 --> 00:17:07,610 They're on the same side of the double bond here. 345 00:17:07,610 --> 00:17:11,170 These are types of optical isomers. 346 00:17:11,170 --> 00:17:13,970 These are the mirror images, the same functional groups, 347 00:17:13,970 --> 00:17:17,560 but in this case, in one orientation, the plus 348 00:17:17,560 --> 00:17:20,390 enantiomer, here's the minus enantiomer. 349 00:17:20,390 --> 00:17:23,630 They're called enantiomers because it comes from the 350 00:17:23,630 --> 00:17:24,970 Greek word for mirror. 351 00:17:24,970 --> 00:17:27,350 So we're using the Greek word for glove and the Greek word 352 00:17:27,350 --> 00:17:28,710 for mirror. 353 00:17:28,710 --> 00:17:30,820 Now we'll talk about the optical activity, and then 354 00:17:30,820 --> 00:17:31,660 we'll take a few notes. 355 00:17:31,660 --> 00:17:33,520 So what's the optical activity? 356 00:17:33,520 --> 00:17:38,800 It turns out that if you put these in aqueous solution, 357 00:17:38,800 --> 00:17:40,840 they will cause the polarization 358 00:17:40,840 --> 00:17:43,260 vector of light to rotate. 359 00:17:43,260 --> 00:17:45,730 So here's a cartoon that shows a light source with 360 00:17:45,730 --> 00:17:48,340 unpolarized light, and then the light goes through a 361 00:17:48,340 --> 00:17:51,670 polarizer, which then forces only 362 00:17:51,670 --> 00:17:53,420 vertically polarized light. 363 00:17:53,420 --> 00:17:55,590 In other words, the electric factor is in the vertical 364 00:17:55,590 --> 00:17:56,630 orientation. 365 00:17:56,630 --> 00:18:01,320 And so now this electric vector enters this tube 366 00:18:01,320 --> 00:18:05,300 containing an aqueous solution of something 367 00:18:05,300 --> 00:18:07,310 that has optical activity. 368 00:18:07,310 --> 00:18:13,280 And the degree of rotation is proportional, obviously, to 369 00:18:13,280 --> 00:18:16,220 the concentration of the chiral species, and also the 370 00:18:16,220 --> 00:18:16,960 path length. 371 00:18:16,960 --> 00:18:19,860 So if you have a dilute solution on a long path, or a 372 00:18:19,860 --> 00:18:22,640 concentrated solution on a short path, it's the number of 373 00:18:22,640 --> 00:18:23,650 collisions. 374 00:18:23,650 --> 00:18:26,730 And ultimately, you have a degree of rotation, et cetera. 375 00:18:26,730 --> 00:18:31,380 And so based on how the electric vector changes is how 376 00:18:31,380 --> 00:18:34,090 we got the names for the various enantiomers, because 377 00:18:34,090 --> 00:18:35,220 we've got to name them somehow. 378 00:18:35,220 --> 00:18:37,550 Otherwise we can't distinguish one from the other. 379 00:18:37,550 --> 00:18:41,140 So it turns out that the way I've drawn this one, with the 380 00:18:41,140 --> 00:18:44,680 amino group in the lower right, and the carboxylic acid 381 00:18:44,680 --> 00:18:47,990 group in the lower left, causes the electric vector to 382 00:18:47,990 --> 00:18:49,310 rotate clockwise. 383 00:18:49,310 --> 00:18:52,450 So I'm going to write h nu, just so that you know, or if 384 00:18:52,450 --> 00:18:55,470 you want to put the electric vector or something. 385 00:18:55,470 --> 00:18:58,650 It rotates page to the right, and so the Latin word for 386 00:18:58,650 --> 00:18:59,700 right is dexter. 387 00:18:59,700 --> 00:19:03,400 So this is called dextrorotatory. 388 00:19:03,400 --> 00:19:08,290 This is the dextrorotatory enantiomer. 389 00:19:08,290 --> 00:19:11,410 So now you've got really nice terminology to use at the 390 00:19:11,410 --> 00:19:14,170 table over the Thanksgiving turkey, all right? 391 00:19:14,170 --> 00:19:17,640 So this is the D-form, D-circle, or, as every 392 00:19:17,640 --> 00:19:20,320 right-handed person knows when speaking to a left-handed 393 00:19:20,320 --> 00:19:23,290 person, this is the positive direction, OK? 394 00:19:23,290 --> 00:19:25,930 And now this one causes an anti-clockwise, or 395 00:19:25,930 --> 00:19:30,070 counterclockwise rotation of light in an 396 00:19:30,070 --> 00:19:31,970 aqueous solution of this. 397 00:19:31,970 --> 00:19:36,010 And rather than use sinister, which is the Latin word for 398 00:19:36,010 --> 00:19:38,220 left, and it has all these negative connotations, they 399 00:19:38,220 --> 00:19:40,345 went to the Slavic, and shows levorotatory. 400 00:19:45,530 --> 00:19:52,040 So this is levorotatory, L-form, or minus N, with 401 00:19:52,040 --> 00:19:54,370 apologies to the left-handed people in the audience. 402 00:19:54,370 --> 00:19:55,870 That's what it's called. 403 00:19:55,870 --> 00:19:56,130 OK. 404 00:19:56,130 --> 00:19:58,900 So these are called enantiomers, and hence, you 405 00:19:58,900 --> 00:20:01,510 understand the choice of Man in the Mirror 406 00:20:01,510 --> 00:20:05,350 for the opening music. 407 00:20:05,350 --> 00:20:09,200 So 19 of the 20 amino acids are chiral. 408 00:20:09,200 --> 00:20:11,860 The only one that's non-chiral, the only 409 00:20:11,860 --> 00:20:14,910 non-chiral amino acid, is glycine. 410 00:20:14,910 --> 00:20:22,820 Glycine has hydrogen as a substituent. 411 00:20:22,820 --> 00:20:26,070 So now you have hydrogens above and below, an amino acid 412 00:20:26,070 --> 00:20:28,730 here, and carboxylic acid here. 413 00:20:28,730 --> 00:20:31,130 And this one is achiral. 414 00:20:31,130 --> 00:20:32,120 This is achiral. 415 00:20:32,120 --> 00:20:37,300 So the other 19 so that's 95% of the amino acids, are 416 00:20:37,300 --> 00:20:40,920 chiral, and they exhibit this interesting behavior. 417 00:20:40,920 --> 00:20:44,220 Now the other interesting piece is that only the 418 00:20:44,220 --> 00:20:45,200 L-enantiomer-- 419 00:20:45,200 --> 00:20:47,680 by and large, there a few exceptions that you can find. 420 00:20:47,680 --> 00:20:49,710 There's some research on this, trying to 421 00:20:49,710 --> 00:20:51,240 find, always the exception. 422 00:20:51,240 --> 00:20:56,040 But by and large, only the L-enantiomer of amino acids 423 00:20:56,040 --> 00:20:57,650 are found in proteins. 424 00:20:57,650 --> 00:21:00,920 So there's no preference in nature for synthesizing one 425 00:21:00,920 --> 00:21:05,440 over the other, but somehow, somewhere, a long time ago, 426 00:21:05,440 --> 00:21:07,950 there was a preference given to the L-enantiomer. 427 00:21:07,950 --> 00:21:13,740 And so all of us have the L-enantiomer present in the 428 00:21:13,740 --> 00:21:15,560 proteins in our bodies. 429 00:21:15,560 --> 00:21:18,570 So I'm going to say only, but you know that there's always 430 00:21:18,570 --> 00:21:19,780 going to be some exception here. 431 00:21:19,780 --> 00:21:26,980 But by and large, only the L-enantiomer of amino acids 432 00:21:26,980 --> 00:21:28,230 found in proteins. 433 00:21:34,150 --> 00:21:36,650 And you're going to see the protein synthesis in a moment, 434 00:21:36,650 --> 00:21:38,720 and try to figure out why that happened. 435 00:21:41,880 --> 00:21:43,740 By the way, carbohydrates, which we're not 436 00:21:43,740 --> 00:21:44,990 going to talk about-- 437 00:21:47,500 --> 00:21:49,280 carbohydrates are chiral as well. 438 00:21:49,280 --> 00:21:56,480 And in sugars, only the D-enantiomer of amino acids 439 00:21:56,480 --> 00:21:57,960 found in sugars. 440 00:22:01,860 --> 00:22:04,660 And you'll see later, this is all important in terms of a 441 00:22:04,660 --> 00:22:06,680 lock and key mechanism. 442 00:22:06,680 --> 00:22:09,070 And there are some L-sugars. 443 00:22:09,070 --> 00:22:11,470 L-sugars you know as invert sugars. 444 00:22:15,130 --> 00:22:18,330 And our bodies don't recognize invert sugars. 445 00:22:18,330 --> 00:22:22,760 Our body apparatus requires that there be D-sugars. 446 00:22:22,760 --> 00:22:26,230 There's some science fiction novella I read many years ago 447 00:22:26,230 --> 00:22:29,950 about this group of people that's marooned on the 448 00:22:29,950 --> 00:22:33,260 proverbial desert island, and it's lush with vegetation, and 449 00:22:33,260 --> 00:22:35,090 they're eating all of these fruits and vegetables and 450 00:22:35,090 --> 00:22:36,420 wasting away. 451 00:22:36,420 --> 00:22:39,890 And at the end of the novel, it comes to be known that this 452 00:22:39,890 --> 00:22:42,910 island, because it was isolated, somehow, back in 453 00:22:42,910 --> 00:22:49,000 time, the plant life there had the opposite enantiomer, and 454 00:22:49,000 --> 00:22:51,630 so their biological apparatus didn't recognize anything. 455 00:22:51,630 --> 00:22:53,160 They were eating all this stuff, and it was just going 456 00:22:53,160 --> 00:22:56,800 right through them with no nutrient value. 457 00:22:56,800 --> 00:23:00,170 So if you're ever marooned, check! 458 00:23:00,170 --> 00:23:03,050 Find out which enantiomer you're eating! 459 00:23:03,050 --> 00:23:04,480 Otherwise you're wasting your time. 460 00:23:07,560 --> 00:23:11,380 Honey has the L-sugar, because bees have a different 461 00:23:11,380 --> 00:23:13,530 biological apparatus. 462 00:23:13,530 --> 00:23:17,720 Now, when we synthesize these things chemically, we can get 463 00:23:17,720 --> 00:23:21,260 both enantiomers coming out of the synthetic apparatus unless 464 00:23:21,260 --> 00:23:23,500 we take pains not to. 465 00:23:23,500 --> 00:23:32,700 And so when both enantiomers are present, we call that 466 00:23:32,700 --> 00:23:37,420 specimen, that's term racemic. 467 00:23:37,420 --> 00:23:40,090 So you have both the dextrorotatory and 468 00:23:40,090 --> 00:23:42,190 levorotatory present. 469 00:23:42,190 --> 00:23:44,570 Now, normally we take the five minutes at the end to talk 470 00:23:44,570 --> 00:23:47,460 about chemistry in the world around us, but this is, you 471 00:23:47,460 --> 00:23:53,090 know, day before Thanksgiving holiday, and we've got a 472 00:23:53,090 --> 00:23:54,770 natural entry point here. 473 00:23:54,770 --> 00:23:59,770 I want to talk about what the consequence here is for human 474 00:23:59,770 --> 00:24:03,770 health that drives directly from chirality. 475 00:24:03,770 --> 00:24:07,240 About 40 years ago, there was a drug developed in Europe 476 00:24:07,240 --> 00:24:09,900 called thalidomide. 477 00:24:09,900 --> 00:24:15,060 And it was developed by a German firm called Chemie 478 00:24:15,060 --> 00:24:16,310 Gruenenthal. 479 00:24:19,440 --> 00:24:20,690 If I can just spell it. 480 00:24:23,080 --> 00:24:26,240 And it was developed as an anticonvulsant. 481 00:24:26,240 --> 00:24:29,950 And it was a sedative, and it had fantastic properties. 482 00:24:29,950 --> 00:24:36,050 Namely, that it was something that you could use in 483 00:24:36,050 --> 00:24:40,430 treatment of people who are very depressive, but they 484 00:24:40,430 --> 00:24:42,330 couldn't kill themselves with this. 485 00:24:42,330 --> 00:24:44,940 If you tried to overdose with thalidomide, you would simply 486 00:24:44,940 --> 00:24:48,230 go into a sleep, and then you could be rescued 487 00:24:48,230 --> 00:24:50,650 Well, that was its original intention. 488 00:24:50,650 --> 00:24:53,570 Just by accident, it was discovered by various people 489 00:24:53,570 --> 00:24:58,460 who were using it that it was a very fine palliative for 490 00:24:58,460 --> 00:24:59,670 morning sickness. 491 00:24:59,670 --> 00:25:02,490 And so women started using it in the first trimester of 492 00:25:02,490 --> 00:25:07,080 their pregnancies in order to calm their morning sickness. 493 00:25:07,080 --> 00:25:11,840 And so there were calls for the importation of this drug 494 00:25:11,840 --> 00:25:13,520 to the United States. 495 00:25:13,520 --> 00:25:15,980 And the FDA said no. 496 00:25:15,980 --> 00:25:17,980 And of course there was an outcry from women's groups 497 00:25:17,980 --> 00:25:20,920 that said, oh, the FDA is just a bunch of men that are 498 00:25:20,920 --> 00:25:23,140 insensitive to women's health issues. 499 00:25:23,140 --> 00:25:25,440 Let's speed this stuff up, let's get it over here. 500 00:25:25,440 --> 00:25:26,470 They're using it in Europe. 501 00:25:26,470 --> 00:25:27,840 What are we doing? 502 00:25:27,840 --> 00:25:30,490 It turns out that this was during the time of President 503 00:25:30,490 --> 00:25:33,580 John Kennedy, and he had appointed the first woman 504 00:25:33,580 --> 00:25:34,920 director of the FDA. 505 00:25:34,920 --> 00:25:37,890 And she said, it hasn't been tested thoroughly. 506 00:25:37,890 --> 00:25:40,600 We're not importing it to the United States. 507 00:25:40,600 --> 00:25:42,580 People got on airplanes, they used post 508 00:25:42,580 --> 00:25:43,710 office, what have you. 509 00:25:43,710 --> 00:25:46,040 They brought it into the United States, and it was used 510 00:25:46,040 --> 00:25:48,620 widely in the United States, And then subsequently was 511 00:25:48,620 --> 00:25:52,020 discovered that this is a teratogen, which causes severe 512 00:25:52,020 --> 00:25:54,450 mutation of the DNA, and children 513 00:25:54,450 --> 00:25:56,330 being born minus limbs. 514 00:25:56,330 --> 00:25:59,190 There were grotesque deformities. 515 00:25:59,190 --> 00:26:02,690 And so the position of the FDA was right. 516 00:26:02,690 --> 00:26:05,190 So you say, well, but didn't they test this stuff? 517 00:26:05,190 --> 00:26:06,400 And they did. 518 00:26:06,400 --> 00:26:08,530 Well, didn't they test it on animal models? 519 00:26:08,530 --> 00:26:10,160 And they did. 520 00:26:10,160 --> 00:26:13,470 Turns out the animal models that they used lacked a 521 00:26:13,470 --> 00:26:16,760 certain enzyme that's present in our bodies, that converts 522 00:26:16,760 --> 00:26:20,750 thalidomide downstream into something that's a teratogen. 523 00:26:20,750 --> 00:26:23,750 It's a really, really sad story. 524 00:26:23,750 --> 00:26:29,920 It turns out now, knowing what we know, only one of the 525 00:26:29,920 --> 00:26:34,540 enantiomers of thalidomide causes birth defects. 526 00:26:34,540 --> 00:26:35,880 Not both. 527 00:26:35,880 --> 00:26:39,580 So racemic thalidomide was loaded with both palliative 528 00:26:39,580 --> 00:26:42,250 and toxic components. 529 00:26:42,250 --> 00:26:46,780 And so this is a powerful lesson of getting the-- 530 00:26:46,780 --> 00:26:52,780 avoiding the toxic enantiomer. 531 00:26:56,520 --> 00:26:58,400 And also, there may be people here who are 532 00:26:58,400 --> 00:26:59,710 opposed to animal testing. 533 00:26:59,710 --> 00:27:01,530 And I understand your concerns. 534 00:27:01,530 --> 00:27:05,120 But we're far from being able to sit with the Shroedinger 535 00:27:05,120 --> 00:27:08,650 equation and a supercomputer and predict the metabolic 536 00:27:08,650 --> 00:27:09,940 activity of these drugs. 537 00:27:09,940 --> 00:27:11,950 And so this is the dilemma for people. 538 00:27:11,950 --> 00:27:13,180 Do you want to test it or not? 539 00:27:13,180 --> 00:27:14,530 Do you want to get these things--? 540 00:27:14,530 --> 00:27:17,880 It's actually coming back now, in the treatment of HIV-AIDS. 541 00:27:17,880 --> 00:27:20,820 It's being used as part of a cocktail with other 542 00:27:20,820 --> 00:27:21,760 medications. 543 00:27:21,760 --> 00:27:24,800 But now we know not to give the racemic form, but only to 544 00:27:24,800 --> 00:27:26,010 give a particular enantiomer. 545 00:27:26,010 --> 00:27:29,970 Another one that is a chiral molecule is Ritalin, which is 546 00:27:29,970 --> 00:27:32,840 used, among other things, for the treatment of ADHD. 547 00:27:32,840 --> 00:27:34,420 And there are some negative side effects 548 00:27:34,420 --> 00:27:35,400 of the use of Ritalin. 549 00:27:35,400 --> 00:27:38,350 And again, it's being discovered that it's only one 550 00:27:38,350 --> 00:27:40,970 of the enantiomers that has the negative side effects. 551 00:27:40,970 --> 00:27:44,740 And so the whole question of chiral molecules is a very, 552 00:27:44,740 --> 00:27:48,690 very hot topic in chemical research. 553 00:27:48,690 --> 00:27:52,380 And so, how do you how direct the synthesis to get to one 554 00:27:52,380 --> 00:27:54,550 enantiomer and not the other? 555 00:27:54,550 --> 00:27:55,840 Catalysis. 556 00:27:55,840 --> 00:27:58,610 Again, which is something that is very important and not very 557 00:27:58,610 --> 00:27:59,580 well understood. 558 00:27:59,580 --> 00:28:01,700 Highly empirical, still. 559 00:28:01,700 --> 00:28:03,970 So all of those lessons that we've 560 00:28:03,970 --> 00:28:05,490 learned are very important. 561 00:28:05,490 --> 00:28:09,160 I think there's a cartoon here that actually shows-- 562 00:28:09,160 --> 00:28:11,680 all right, so here's the example. 563 00:28:11,680 --> 00:28:14,010 This is a molecule that's chiral, 564 00:28:14,010 --> 00:28:14,990 and it's very primitive. 565 00:28:14,990 --> 00:28:16,760 You've got a square and a triangle and a 566 00:28:16,760 --> 00:28:18,000 circle and so on. 567 00:28:18,000 --> 00:28:20,170 And you see, both of these have the same chemical 568 00:28:20,170 --> 00:28:20,990 properties. 569 00:28:20,990 --> 00:28:24,370 But when you're looking at this in terms of biological 570 00:28:24,370 --> 00:28:27,360 activity in the human body, you can think about a lot of 571 00:28:27,360 --> 00:28:29,930 these interactions as lock and key. 572 00:28:29,930 --> 00:28:31,990 Now, there aren't these little holes here. 573 00:28:31,990 --> 00:28:35,100 It's not putting a square peg in a round hole versus what 574 00:28:35,100 --> 00:28:37,070 are they really trying to model here? 575 00:28:37,070 --> 00:28:41,100 They're trying to model the types of secondary reactions. 576 00:28:41,100 --> 00:28:44,470 So for example, there could be a polar center here, and this 577 00:28:44,470 --> 00:28:47,670 could be charged negatively, and this could be charged 578 00:28:47,670 --> 00:28:51,180 positively, and so they will be attracted coulombically. 579 00:28:51,180 --> 00:28:55,250 Maybe this has a polar end, and this has a dipole, and 580 00:28:55,250 --> 00:28:56,450 they'll be attracted. 581 00:28:56,450 --> 00:28:59,690 Maybe this is nonpolar, and this is nonpolar, so they all 582 00:28:59,690 --> 00:29:02,930 fit, whereas if you turn it around, you've got something 583 00:29:02,930 --> 00:29:06,320 that's positively charged here, and this thing's a 584 00:29:06,320 --> 00:29:08,730 dipole, there's no adhesion. 585 00:29:08,730 --> 00:29:10,450 So that's where this lock-and-key 586 00:29:10,450 --> 00:29:12,610 idea comes into play. 587 00:29:12,610 --> 00:29:15,510 And so what we're going to do later on is to figure out how 588 00:29:15,510 --> 00:29:19,420 to match things up in terms of dipole-dipole interactions, 589 00:29:19,420 --> 00:29:23,810 coulombic interactions, and so forth. 590 00:29:23,810 --> 00:29:24,810 OK. 591 00:29:24,810 --> 00:29:26,160 So what are the properties now? 592 00:29:26,160 --> 00:29:29,300 Let's look at the properties of these things as just 593 00:29:29,300 --> 00:29:30,120 straight chemicals. 594 00:29:30,120 --> 00:29:33,840 So we had amino acid, I had the solid neutral form of the 595 00:29:33,840 --> 00:29:34,980 amino acid. 596 00:29:34,980 --> 00:29:36,230 What are its properties? 597 00:29:40,030 --> 00:29:40,880 Not the protein. 598 00:29:40,880 --> 00:29:44,580 Properties of the amino acid. 599 00:29:44,580 --> 00:29:44,830 OK. 600 00:29:44,830 --> 00:29:47,922 So first of all, they are solids at room temperature. 601 00:29:54,120 --> 00:29:55,720 And why would we do that? 602 00:29:55,720 --> 00:29:56,470 Well, because look. 603 00:29:56,470 --> 00:29:59,600 You've got hydrogen bonding capability here, and that 604 00:29:59,600 --> 00:30:03,830 hydrogen bonding capability allows it to form bonds great 605 00:30:03,830 --> 00:30:07,230 enough to overcome thermal energy. 606 00:30:07,230 --> 00:30:09,920 Molecules like this, do you think they form crystalline 607 00:30:09,920 --> 00:30:13,840 solids or amorphous solids? 608 00:30:13,840 --> 00:30:15,340 They're small enough that-- 609 00:30:15,340 --> 00:30:17,770 this one looks a lot like methane, doesn't it? 610 00:30:17,770 --> 00:30:21,890 Looks like methane with a couple of extra things. 611 00:30:21,890 --> 00:30:24,120 But from a distance, it's a sphere. 612 00:30:24,120 --> 00:30:26,440 maybe A little bit oblate, but it's a sphere. 613 00:30:26,440 --> 00:30:29,000 So these things form crystalline solids as opposed 614 00:30:29,000 --> 00:30:32,030 to amorphous solids. 615 00:30:32,030 --> 00:30:34,690 Their optical properties, I've already shown you. 616 00:30:34,690 --> 00:30:35,940 They're colorless. 617 00:30:38,360 --> 00:30:39,260 They're not good absorbers. 618 00:30:39,260 --> 00:30:42,480 Where's the covalent bonds with tight electrons? 619 00:30:42,480 --> 00:30:45,850 So there's no reason to have excitation and color. 620 00:30:45,850 --> 00:30:48,590 And then, they're moderately soluble in water. 621 00:30:55,760 --> 00:30:57,930 And that water chemistry is what we're 622 00:30:57,930 --> 00:30:59,690 going to turn to next. 623 00:30:59,690 --> 00:31:02,850 So now I want to look at how they behave in water. 624 00:31:02,850 --> 00:31:05,660 And where I'm going with this is to show you the first 625 00:31:05,660 --> 00:31:08,610 stages of how we animate matter. 626 00:31:08,610 --> 00:31:10,480 Because I talk about inanimate matter. 627 00:31:10,480 --> 00:31:11,880 We are animate matter. 628 00:31:11,880 --> 00:31:13,760 Where does the animation come from? 629 00:31:13,760 --> 00:31:16,320 What's the chemical origin of our animation? 630 00:31:16,320 --> 00:31:18,570 How is it that I can do this? 631 00:31:18,570 --> 00:31:19,750 See, you're looking at changes in the 632 00:31:19,750 --> 00:31:22,080 conformation of a polymer. 633 00:31:22,080 --> 00:31:23,510 That's all you're doing. 634 00:31:23,510 --> 00:31:25,580 You're saying, well, how-- 635 00:31:25,580 --> 00:31:28,000 he's moving fast. What's the Debye frequency? 636 00:31:28,000 --> 00:31:30,390 It's 10 trillion times a second. 637 00:31:30,390 --> 00:31:34,510 10 trillion times a second the atoms vibrate in my body, and 638 00:31:34,510 --> 00:31:36,950 the speed at which I'm rotating my hand, compared to 639 00:31:36,950 --> 00:31:43,690 10 trillion times a second, very slow, right? 640 00:31:43,690 --> 00:31:48,250 Which actually explains why we talk at the speed we do. 641 00:31:48,250 --> 00:31:51,270 And why is it that a human being can only run-- 642 00:31:51,270 --> 00:31:55,820 or not only run, but runs at the speed that he or she does? 643 00:31:55,820 --> 00:31:58,690 It has to do with the chemistry. 644 00:31:58,690 --> 00:32:01,430 With the Debye frequency, and what the skeleton can do-- 645 00:32:01,430 --> 00:32:04,905 I mean, why aren't human beings 40 feet tall? 646 00:32:04,905 --> 00:32:07,890 I mean, stand back here and-- all right-- 647 00:32:07,890 --> 00:32:09,770 we're going to create this universe. 648 00:32:09,770 --> 00:32:13,440 Why are we this tall, and not 40 feet tall? 649 00:32:13,440 --> 00:32:17,090 Because make a skeleton 40 feet tall would be chemically 650 00:32:17,090 --> 00:32:20,320 very difficult. 651 00:32:20,320 --> 00:32:22,180 It's all chemistry. 652 00:32:22,180 --> 00:32:24,490 The rest, as we know, is stamp collecting. 653 00:32:24,490 --> 00:32:28,310 OK, so now let's look at the properties of the 654 00:32:28,310 --> 00:32:29,430 amino acids and water. 655 00:32:29,430 --> 00:32:31,760 So I'm going to write them again in a different form. 656 00:32:31,760 --> 00:32:33,500 So here I'm going to put the H2N. 657 00:32:33,500 --> 00:32:35,150 Here's the amino acid N. 658 00:32:35,150 --> 00:32:37,040 Here's the central carbon. 659 00:32:37,040 --> 00:32:39,170 And I'm going to put the hydrogen, instead of writing 660 00:32:39,170 --> 00:32:40,520 it down here, this is the carbon 661 00:32:40,520 --> 00:32:41,990 with its little hydrogen. 662 00:32:41,990 --> 00:32:45,410 This is the carboxylic acid N, and then the 663 00:32:45,410 --> 00:32:47,070 substituent group is above. 664 00:32:47,070 --> 00:32:48,130 So this is again the thing. 665 00:32:48,130 --> 00:32:51,040 By the way, there are two carbons here, agreed? 666 00:32:51,040 --> 00:32:55,190 And the central carbon is also known as the alpha-carbon. 667 00:32:55,190 --> 00:32:58,010 This is the alpha-carbon. 668 00:32:58,010 --> 00:32:59,800 That's the beta-carbon, I bet. 669 00:32:59,800 --> 00:33:00,140 All right. 670 00:33:00,140 --> 00:33:02,400 So now what I'm going to do is, I'm going to dissolve this 671 00:33:02,400 --> 00:33:04,510 in water at neutral pH. 672 00:33:07,850 --> 00:33:09,150 And what happens? 673 00:33:09,150 --> 00:33:13,160 What happens is that once this thing solvates, the proton 674 00:33:13,160 --> 00:33:16,930 falls off the carboxylic end and comes over and attaches to 675 00:33:16,930 --> 00:33:20,530 that electron pair at the amino acid end. 676 00:33:20,530 --> 00:33:23,150 And we end up with this, at neutral pH. 677 00:33:23,150 --> 00:33:29,680 H3NCHCOO, and the substituent is a spectator here. 678 00:33:29,680 --> 00:33:32,860 Well, I lost a proton, so this is locally negative. 679 00:33:32,860 --> 00:33:36,000 And I gained a proton with its charge over here. 680 00:33:36,000 --> 00:33:37,490 So this is locally positive. 681 00:33:37,490 --> 00:33:38,670 I conserve charge. 682 00:33:38,670 --> 00:33:42,010 This is not neutral and this is not neutral, but it has a 683 00:33:42,010 --> 00:33:45,010 negative end and a positive end, and it's not a dipole. 684 00:33:45,010 --> 00:33:48,030 I mean, this is negative ion-like and 685 00:33:48,030 --> 00:33:50,270 this is positive ion-like. 686 00:33:50,270 --> 00:34:01,160 So let's say, net neutral locally positive and negative. 687 00:34:01,160 --> 00:34:04,090 And just as we've fallen in love with some German 688 00:34:04,090 --> 00:34:06,790 terminology for words like bremsstrahlung, we have a 689 00:34:06,790 --> 00:34:08,460 German word for this one. 690 00:34:08,460 --> 00:34:13,910 This is like a twin ion, or it's like a hermaphrodite dual 691 00:34:13,910 --> 00:34:15,810 gender, so this is called zwitterion. 692 00:34:19,260 --> 00:34:20,960 It's got both genders, if you like. 693 00:34:20,960 --> 00:34:23,240 It's positive and negative. 694 00:34:23,240 --> 00:34:24,090 OK. 695 00:34:24,090 --> 00:34:26,600 So there's zwitterion. 696 00:34:26,600 --> 00:34:28,160 And this is the way that we start to 697 00:34:28,160 --> 00:34:29,800 introduce the dynamic behaviors. 698 00:34:29,800 --> 00:34:30,800 So now I'm going to show you how to make 699 00:34:30,800 --> 00:34:32,750 something come to life. 700 00:34:32,750 --> 00:34:35,680 So what we're going to do, is we're going to show how this 701 00:34:35,680 --> 00:34:39,020 zwitterion can respond to changes in its environment. 702 00:34:39,020 --> 00:34:43,870 And we're going to invoke in order to do is to say that to 703 00:34:43,870 --> 00:34:54,496 impart animation, we invoke the le Chatelier principle. 704 00:34:57,710 --> 00:35:01,030 It's sort of like Newton's third law for chemistry. 705 00:35:01,030 --> 00:35:02,180 You know Newton's third law. 706 00:35:02,180 --> 00:35:04,220 Every action, there's a reaction. 707 00:35:04,220 --> 00:35:08,620 So le Chatelier was a French engineer, but his name is 708 00:35:08,620 --> 00:35:11,070 associated with an important chemical principle. 709 00:35:11,070 --> 00:35:14,460 And it basically says that if you disturb a chemical system, 710 00:35:14,460 --> 00:35:16,530 the chemical system will respond in such a way as to 711 00:35:16,530 --> 00:35:18,250 minimize the disturbance. 712 00:35:18,250 --> 00:35:20,910 So the example I'm going to give is, I'm going to start 713 00:35:20,910 --> 00:35:24,350 with a neutral pH, and I'm going to change the pH. 714 00:35:24,350 --> 00:35:26,950 And then the zwitterion is going to respond to minimize 715 00:35:26,950 --> 00:35:27,730 the disturbance. 716 00:35:27,730 --> 00:35:30,560 In other words, if I drop the pH, zwitterion is going to try 717 00:35:30,560 --> 00:35:33,460 to raise the pH back to what it was before. 718 00:35:33,460 --> 00:35:35,640 And in doing so, I think you're going to start to see 719 00:35:35,640 --> 00:35:37,260 how we can get animation. 720 00:35:37,260 --> 00:35:40,760 So it's sort of like that a chemical disturbance-- 721 00:35:43,400 --> 00:35:45,490 this is the le Chatelier principle. 722 00:35:45,490 --> 00:35:50,610 Chemical disturbance is mitigated 723 00:35:50,610 --> 00:35:53,745 by a chemical response. 724 00:35:56,890 --> 00:35:58,920 So here's the example that we're going to use. 725 00:35:58,920 --> 00:36:01,320 We're going to say, let's take something and 726 00:36:01,320 --> 00:36:03,440 radically change the pH. 727 00:36:03,440 --> 00:36:07,230 So let's drop the pH. 728 00:36:10,010 --> 00:36:13,320 So drop a pH means, the proton concentration 729 00:36:13,320 --> 00:36:14,570 is going to go up. 730 00:36:17,010 --> 00:36:20,730 So how would zwitterion respond if it wants to reduce 731 00:36:20,730 --> 00:36:22,750 the proton concentration? 732 00:36:22,750 --> 00:36:25,410 Well, it's going to try to gobble up the protons. 733 00:36:25,410 --> 00:36:26,710 Well, how's it going to do that? 734 00:36:26,710 --> 00:36:29,400 Well, we know that there's a proton attachment site. 735 00:36:29,400 --> 00:36:31,590 Look, there's a proton attachment site at the 736 00:36:31,590 --> 00:36:32,830 carboxylic acid end. 737 00:36:32,830 --> 00:36:33,310 How do we know? 738 00:36:33,310 --> 00:36:35,410 Because it used to have a proton there. 739 00:36:35,410 --> 00:36:38,090 So it's going to go and vacuum up protons to try to bring the 740 00:36:38,090 --> 00:36:40,120 pH back to what it was before. 741 00:36:40,120 --> 00:36:41,540 So let's look at that reaction. 742 00:36:41,540 --> 00:36:48,120 So here's H3NCHCOO minus plus. 743 00:36:48,120 --> 00:36:50,170 So this is neutral zwitterion. 744 00:36:50,170 --> 00:36:54,410 And what it's going to do in response to the increase in 745 00:36:54,410 --> 00:36:57,910 proton concentration is try to gobble these up. 746 00:36:57,910 --> 00:37:01,605 And the following is the result. 747 00:37:04,790 --> 00:37:09,340 That proton is now going to attach here, and cap that 748 00:37:09,340 --> 00:37:10,360 negative end. 749 00:37:10,360 --> 00:37:12,840 So now we've got a proton on this end, and we've added a 750 00:37:12,840 --> 00:37:14,710 proton at the other end. 751 00:37:14,710 --> 00:37:17,380 So what's happened to the neutrality of zwitterion? 752 00:37:17,380 --> 00:37:18,340 It's lost! 753 00:37:18,340 --> 00:37:24,190 Now zwitterion is net positive, but we've started 754 00:37:24,190 --> 00:37:25,300 gobbling up protons. 755 00:37:25,300 --> 00:37:27,410 So this reaction is called protonation. 756 00:37:31,030 --> 00:37:32,950 And the reverse reaction is deprotonation. 757 00:37:38,730 --> 00:37:42,270 And this is messy, all these darn characters. 758 00:37:42,270 --> 00:37:45,480 So I'm going to write the neutral zwitterion as just HA. 759 00:37:45,480 --> 00:37:47,810 There's the proton here, and the rest of this 760 00:37:47,810 --> 00:37:49,350 stuff is just details. 761 00:37:49,350 --> 00:37:50,360 So that's A. 762 00:37:50,360 --> 00:37:56,210 So HA plus H plus gives me this thing here, which is HAH 763 00:37:56,210 --> 00:37:58,270 plus there. 764 00:37:58,270 --> 00:37:59,650 Isn't that cleaner? 765 00:37:59,650 --> 00:38:00,940 That's a lot easier to read. 766 00:38:00,940 --> 00:38:02,640 And we can write an equilibrium 767 00:38:02,640 --> 00:38:03,900 constant for that reaction. 768 00:38:03,900 --> 00:38:06,640 I'm going to call this reaction 1. 769 00:38:06,640 --> 00:38:10,200 In reaction 1, I can write K1. 770 00:38:10,200 --> 00:38:13,630 And it's written, the convention is that you always 771 00:38:13,630 --> 00:38:16,840 write the reaction constant for the 772 00:38:16,840 --> 00:38:18,220 deprotonation reaction. 773 00:38:18,220 --> 00:38:19,860 So I'm going to write the reaction constant for this 774 00:38:19,860 --> 00:38:22,220 reaction from right to left. 775 00:38:22,220 --> 00:38:23,990 So that's going to be this. 776 00:38:23,990 --> 00:38:32,830 H plus over HA divided by concentration of HA H plus. 777 00:38:32,830 --> 00:38:35,570 And then we're going to bring Sorensen to the party, and 778 00:38:35,570 --> 00:38:40,150 take logarithms, and make it nice and clean. 779 00:38:40,150 --> 00:38:43,210 As we know, when Sorensen enters the room, he 780 00:38:43,210 --> 00:38:44,540 straightens things out. 781 00:38:44,540 --> 00:38:48,290 And so this will then become PK, and if I take the log base 782 00:38:48,290 --> 00:38:50,950 10 of this, I'm going to end up with minus log base 10 of 783 00:38:50,950 --> 00:38:53,070 H, which then will be PH. 784 00:38:53,070 --> 00:38:56,310 And then this flips over with the minus sign, and becomes 785 00:38:56,310 --> 00:39:03,030 log base 10 of the ratio of protonated zwitterion over 786 00:39:03,030 --> 00:39:06,020 deprotonated zwitterion. 787 00:39:06,020 --> 00:39:06,920 And this is known as the 788 00:39:06,920 --> 00:39:08,690 Henderson-Hasselbalch equation. 789 00:39:13,310 --> 00:39:14,250 And what does it answer? 790 00:39:14,250 --> 00:39:16,620 It answers the question, you tell me what the pH of the 791 00:39:16,620 --> 00:39:20,110 system is, and I'll tell you what the ratio of protonated 792 00:39:20,110 --> 00:39:22,920 to deprotonated is, because the PK is the 793 00:39:22,920 --> 00:39:24,760 function of the R group. 794 00:39:24,760 --> 00:39:27,230 So different R groups have different PKAs, and they'll 795 00:39:27,230 --> 00:39:28,480 respond differently. 796 00:39:28,480 --> 00:39:32,400 Some are very aggressive, and some are not so aggressive. 797 00:39:32,400 --> 00:39:33,740 And look at what happens. 798 00:39:33,740 --> 00:39:39,800 At one end, when we have neutral pH, we have all of the 799 00:39:39,800 --> 00:39:41,600 zwitterions sitting here. 800 00:39:41,600 --> 00:39:44,940 And as we go to higher and higher pH, more and more of 801 00:39:44,940 --> 00:39:47,960 the neutral zwitterion converts to the protonated 802 00:39:47,960 --> 00:39:49,390 zwitterion. 803 00:39:49,390 --> 00:39:53,830 And in the extreme, when I've got very, very high proton 804 00:39:53,830 --> 00:39:57,220 concentration, I will protonate all the zwitterion. 805 00:39:57,220 --> 00:39:58,700 I'll protonate it out of existence. 806 00:39:58,700 --> 00:40:03,520 And the only amino acid that exists is fully protonated. 807 00:40:03,520 --> 00:40:08,150 So I've got a sliding scale from 100% deprotonated to a 808 00:40:08,150 --> 00:40:09,490 100% protonated. 809 00:40:09,490 --> 00:40:12,300 Well, somewhere along this scale is 50-50. 810 00:40:12,300 --> 00:40:15,140 And what happens when I've got equal amounts of protonated to 811 00:40:15,140 --> 00:40:15,890 deprotonated? 812 00:40:15,890 --> 00:40:18,520 That means the concentration of protonated equals the 813 00:40:18,520 --> 00:40:20,200 concentration of deprotonated. 814 00:40:20,200 --> 00:40:24,850 I have the log of 1, which is 0, and that's the pH at PK1. 815 00:40:24,850 --> 00:40:27,650 So now you see physically what PK1 means. 816 00:40:27,650 --> 00:40:30,810 It's the pH at which you're halfway in between, which 817 00:40:30,810 --> 00:40:31,470 makes sense. 818 00:40:31,470 --> 00:40:34,000 If I wanted to characterize something, it has values 819 00:40:34,000 --> 00:40:37,360 between 0 and 100, I'd give you the value at 50, and you 820 00:40:37,360 --> 00:40:40,170 know, it varies around 50. 821 00:40:40,170 --> 00:40:42,760 Either 50 plus 50, 50 minus 50. 822 00:40:42,760 --> 00:40:45,010 So that's what the PK is. 823 00:40:45,010 --> 00:40:46,130 Good. 824 00:40:46,130 --> 00:40:48,600 Now let's do the same thing for the opposite side. 825 00:40:48,600 --> 00:40:54,310 Let's, instead of a sudden drop in pH, let's look at a 826 00:40:54,310 --> 00:41:01,190 sudden rise in pH. 827 00:41:01,190 --> 00:41:03,450 Now you see, just to finish the point. 828 00:41:03,450 --> 00:41:05,070 Look at what happens here. 829 00:41:05,070 --> 00:41:08,750 What I'm trying to show you is that this change in pH caused 830 00:41:08,750 --> 00:41:10,070 this molecule to change. 831 00:41:13,330 --> 00:41:17,130 you I mean, this could be in your stomach. 832 00:41:17,130 --> 00:41:21,350 And now you drink some coffee, or you drink some cola, and 833 00:41:21,350 --> 00:41:25,210 the pH goes way, way down, because you've drunk something 834 00:41:25,210 --> 00:41:26,310 that's acidic. 835 00:41:26,310 --> 00:41:28,430 Well, there are functional groups in the lining of your 836 00:41:28,430 --> 00:41:32,580 stomach that are going to now start protonating. 837 00:41:32,580 --> 00:41:34,440 And when they protonate, they're going to change. 838 00:41:34,440 --> 00:41:36,830 This could have been bonding to something, right? 839 00:41:36,830 --> 00:41:40,490 COO minus could've been bonding to some other molecule 840 00:41:40,490 --> 00:41:41,860 that's locally plus. 841 00:41:41,860 --> 00:41:44,430 When the proton comes in here and caps it, 842 00:41:44,430 --> 00:41:47,210 that bond is broken! 843 00:41:47,210 --> 00:41:50,230 And that's the beginning of animation. 844 00:41:50,230 --> 00:41:51,900 So that when I drink something, and all of a 845 00:41:51,900 --> 00:41:55,170 sudden, my stomach goes into action. 846 00:41:55,170 --> 00:41:57,660 Well, we're going to have to process this stuff. 847 00:41:57,660 --> 00:42:00,520 Have to turn on some switches here. 848 00:42:00,520 --> 00:42:02,450 It's not my brain that's doing it! 849 00:42:02,450 --> 00:42:05,360 It's not that the brain gets all these sensor signals. 850 00:42:05,360 --> 00:42:06,800 We couldn't function that way. 851 00:42:06,800 --> 00:42:10,620 We're functioning just by these things acting right 852 00:42:10,620 --> 00:42:11,810 there at the site. 853 00:42:11,810 --> 00:42:14,920 This is the origin of animation. 854 00:42:14,920 --> 00:42:19,090 I'm telling you that this is the secret of life. 855 00:42:19,090 --> 00:42:20,490 I can't tell you the meaning of life. 856 00:42:20,490 --> 00:42:22,520 You have to go somewhere else to answer that question. 857 00:42:22,520 --> 00:42:24,470 But I can tell you where life comes from. 858 00:42:24,470 --> 00:42:24,890 There it is. 859 00:42:24,890 --> 00:42:28,220 So now, sudden rise in pH, this means that the proton 860 00:42:28,220 --> 00:42:29,740 concentration goes way down. 861 00:42:33,170 --> 00:42:35,360 See, zwitterion is like one of these friends you might have. 862 00:42:35,360 --> 00:42:37,510 Do you have any friends that are, what do 863 00:42:37,510 --> 00:42:39,350 you call them, rescuers? 864 00:42:39,350 --> 00:42:41,810 You know, if they see anything wrong, they're the ones that 865 00:42:41,810 --> 00:42:42,980 get involved? 866 00:42:42,980 --> 00:42:45,180 They've got to help everything? 867 00:42:45,180 --> 00:42:48,190 In the extreme, they're quite meddlesome. 868 00:42:48,190 --> 00:42:49,690 Well, this is what zwitterion is like. 869 00:42:49,690 --> 00:42:53,190 See, zwitterion sees a sudden drop in pH and goes, I'm 870 00:42:53,190 --> 00:42:54,340 zwitterion! 871 00:42:54,340 --> 00:42:55,540 I can help! 872 00:42:55,540 --> 00:42:59,000 I know what to do, because I'm zwitterion! 873 00:42:59,000 --> 00:43:00,310 I fix things! 874 00:43:00,310 --> 00:43:03,840 And I'm conflict-averse, I don't like this! 875 00:43:03,840 --> 00:43:04,190 OK. 876 00:43:04,190 --> 00:43:06,640 Imagine you are zwitterion. 877 00:43:06,640 --> 00:43:09,610 So here's zwitterion, sitting there, minding its own 878 00:43:09,610 --> 00:43:09,890 business 879 00:43:09,890 --> 00:43:10,170 [BREAK IN AUDIO] 880 00:43:10,170 --> 00:43:11,040 PROFESSOR: --for a minute. 881 00:43:11,040 --> 00:43:11,300 Why? 882 00:43:11,300 --> 00:43:14,100 Because it's in a neutral pH solution. 883 00:43:14,100 --> 00:43:15,410 Minding its own business. 884 00:43:15,410 --> 00:43:17,140 That's a chemical joke. 885 00:43:17,140 --> 00:43:17,510 All right. 886 00:43:17,510 --> 00:43:18,910 So there's zwitterion, just sitting there, 887 00:43:18,910 --> 00:43:19,900 minding his own business. 888 00:43:19,900 --> 00:43:27,100 And all of a sudden, the pH rises, and the proton 889 00:43:27,100 --> 00:43:28,270 concentration drops. 890 00:43:28,270 --> 00:43:30,500 So now we've got an abundance of hydroxyls. 891 00:43:30,500 --> 00:43:32,080 We're in an aqueous solution. 892 00:43:32,080 --> 00:43:34,080 So the zwitterion looks around and says, I've got to fix 893 00:43:34,080 --> 00:43:37,360 this, but there's no hydroxyl attachment site! 894 00:43:37,360 --> 00:43:40,070 So the zwitterion can't gobble up the hydroxyls. 895 00:43:40,070 --> 00:43:42,470 So what's the zwitterion do instead? 896 00:43:42,470 --> 00:43:44,380 Instead, it starts shedding protons. 897 00:43:44,380 --> 00:43:48,070 Because if it sheds protons, then what can happen is, if it 898 00:43:48,070 --> 00:43:51,900 forms this plus proton, then the proton can react with 899 00:43:51,900 --> 00:43:57,160 hydroxyl to form water, and then shoot the pH back to near 900 00:43:57,160 --> 00:43:58,680 neutrality. 901 00:43:58,680 --> 00:44:02,810 So let's dump the proton here, and we'll just end up with H2 902 00:44:02,810 --> 00:44:08,530 and CHCOO minus with the R group. 903 00:44:08,530 --> 00:44:11,930 So this is deprotonation in order to address the sudden 904 00:44:11,930 --> 00:44:12,880 rise in pH. 905 00:44:12,880 --> 00:44:14,860 And now we can write a K2. 906 00:44:14,860 --> 00:44:20,640 Let's call this reaction 2, and with K2, since it's a 907 00:44:20,640 --> 00:44:22,880 deprotonation reaction right away, we can just go ahead and 908 00:44:22,880 --> 00:44:25,400 write, this is going to be H plus. 909 00:44:25,400 --> 00:44:26,130 And what's left? 910 00:44:26,130 --> 00:44:30,240 This is just a denuded, deprotonated zwitterion, just 911 00:44:30,240 --> 00:44:33,760 the A minus, all over neutral zwitterion. 912 00:44:33,760 --> 00:44:35,250 And it looks like this. 913 00:44:35,250 --> 00:44:43,190 And we can invoke Sorensen and get PK2 equals pH plus log 914 00:44:43,190 --> 00:44:47,620 base 10 of the neutral zwitterion over the 915 00:44:47,620 --> 00:44:50,390 deprotonated zwitterion. 916 00:44:50,390 --> 00:44:51,150 And there you go. 917 00:44:51,150 --> 00:44:54,000 And then, of course, that 50-50 concentration of 918 00:44:54,000 --> 00:44:58,570 deprotonation, the pH gives you the value of PK2. 919 00:44:58,570 --> 00:45:01,300 And now, at one end, I get deprotonated. 920 00:45:01,300 --> 00:45:02,710 The other end, I get fully protonated, 921 00:45:02,710 --> 00:45:03,650 right in the middle. 922 00:45:03,650 --> 00:45:07,830 I get the 100% zwitterion. 923 00:45:07,830 --> 00:45:11,010 I said at neutral pH, but that doesn't mean 7. 924 00:45:11,010 --> 00:45:14,875 It means the pH at which this particular species is stable. 925 00:45:14,875 --> 00:45:17,680 And that's different from 7, and it's somewhere in 926 00:45:17,680 --> 00:45:18,970 between, isn't it? 927 00:45:18,970 --> 00:45:21,790 Because if I go to very acidic solutions, I 928 00:45:21,790 --> 00:45:23,930 will start to protonate. 929 00:45:23,930 --> 00:45:26,830 If I go to alkaline solutions, I'll deprotonate. 930 00:45:26,830 --> 00:45:28,110 So somewhere in between. 931 00:45:28,110 --> 00:45:29,420 And that somewhere in between is called 932 00:45:29,420 --> 00:45:31,260 the isoelectric point. 933 00:45:31,260 --> 00:45:33,470 The isoelectric point is the place at 934 00:45:33,470 --> 00:45:35,660 which we get the neutral. 935 00:45:35,660 --> 00:45:39,560 So that's HAmax. 936 00:45:39,560 --> 00:45:43,710 The concentration of this is maximal at the isoelectric 937 00:45:43,710 --> 00:45:51,780 point, and that's called P sub I, and that's given by PK1 938 00:45:51,780 --> 00:45:55,516 plus PK2, divided by 2. 939 00:45:55,516 --> 00:45:57,620 And that's it. 940 00:45:57,620 --> 00:45:58,200 You don't have to run it. 941 00:45:58,200 --> 00:45:59,580 We're done. 942 00:45:59,580 --> 00:46:00,450 Thank you. 943 00:46:00,450 --> 00:46:01,540 OK. 944 00:46:01,540 --> 00:46:03,900 So this is the simple story. 945 00:46:03,900 --> 00:46:07,395 It gets more complicated if, for example, the R group can 946 00:46:07,395 --> 00:46:09,290 protonate or deprotonate. 947 00:46:09,290 --> 00:46:12,240 So now we got two or three-ring circus. 948 00:46:12,240 --> 00:46:13,020 It gets more interesting. 949 00:46:13,020 --> 00:46:15,270 But this is the start, and there's some homework problems 950 00:46:15,270 --> 00:46:16,670 that will help you muddle through. 951 00:46:16,670 --> 00:46:17,010 OK. 952 00:46:17,010 --> 00:46:19,710 So I think this is a good place to switch into the final 953 00:46:19,710 --> 00:46:20,290 five minutes. 954 00:46:20,290 --> 00:46:21,520 So here's the titration curve. 955 00:46:21,520 --> 00:46:23,650 I'll show that at the beginning of the next lecture. 956 00:46:23,650 --> 00:46:23,950 OK. 957 00:46:23,950 --> 00:46:25,700 So now let's talk about kinetics. 958 00:46:25,700 --> 00:46:29,050 And the extreme in kinetics, I said, is an explosion. 959 00:46:29,050 --> 00:46:33,560 And we're coming upon December 6, which is the anniversary of 960 00:46:33,560 --> 00:46:37,260 the largest explosion in the history of the world before 961 00:46:37,260 --> 00:46:38,390 the nuclear age. 962 00:46:38,390 --> 00:46:41,880 And it occurred in 1917, and Halifax Harbor, Canada, at 963 00:46:41,880 --> 00:46:45,030 that time was a British colony, and therefore Canada's 964 00:46:45,030 --> 00:46:47,110 foreign policy was dictated by Britain, which was 965 00:46:47,110 --> 00:46:48,300 involved in a war. 966 00:46:48,300 --> 00:46:51,170 And there was a French supply ship and a relief ship, and 967 00:46:51,170 --> 00:46:53,420 they collided in Halifax Harbor. 968 00:46:53,420 --> 00:46:56,220 This is what the French supply ship had on it. 969 00:46:56,220 --> 00:46:58,750 Notice 20,000 tons of TNT. 970 00:46:58,750 --> 00:47:03,810 At 8:45 AM, the Mont-Blanc is hit by the Imo. 971 00:47:03,810 --> 00:47:08,590 But the TNT was not ignited, and instead we ended with 972 00:47:08,590 --> 00:47:11,450 sparks and a fire. 973 00:47:11,450 --> 00:47:14,310 By the way, this is TNT. 974 00:47:14,310 --> 00:47:17,170 If you look, this is toluene. 975 00:47:17,170 --> 00:47:18,520 Toluene is methylbenzene. 976 00:47:18,520 --> 00:47:19,840 It's just the methyl group. 977 00:47:19,840 --> 00:47:22,060 And this is trinitrotoluene. 978 00:47:22,060 --> 00:47:24,810 And if you go to Wikipedia, Wikipedia gives this formula, 979 00:47:24,810 --> 00:47:26,320 which is wrong. 980 00:47:26,320 --> 00:47:28,810 The methyl group is missing here. 981 00:47:28,810 --> 00:47:29,920 Just a word to the wise. 982 00:47:29,920 --> 00:47:32,870 Be careful when you use that tool, I put 983 00:47:32,870 --> 00:47:33,760 in quotation marks. 984 00:47:33,760 --> 00:47:36,680 Because it's worth about as much as you pay for it, which 985 00:47:36,680 --> 00:47:39,730 is why we teach you to use the bibliographic things. 986 00:47:39,730 --> 00:47:41,800 OK, so there it is, right here. 987 00:47:41,800 --> 00:47:42,720 I didn't make this up. 988 00:47:42,720 --> 00:47:43,760 Look at this. 989 00:47:43,760 --> 00:47:45,730 Completely wrong. 990 00:47:45,730 --> 00:47:50,110 Anyway, so what happens? 991 00:47:50,110 --> 00:47:52,330 "The crew of the Mont-Blanc, aware of their cargo, 992 00:47:52,330 --> 00:47:54,830 immediately took the lifeboats, screaming warnings 993 00:47:54,830 --> 00:47:56,160 that no one heeded. 994 00:47:56,160 --> 00:47:57,500 They rode for Dartmouth"-- 995 00:47:57,500 --> 00:47:59,970 this is across the channel from Halifax-- 996 00:47:59,970 --> 00:48:02,890 "leaving the now furiously burning ship to drift towards 997 00:48:02,890 --> 00:48:06,150 Halifax, propelled in that direction by the Imo's impact. 998 00:48:06,150 --> 00:48:09,790 The Mont-Blanc drifted by a Halifax Pier, brushing it and 999 00:48:09,790 --> 00:48:11,310 setting it ablaze. 1000 00:48:11,310 --> 00:48:14,120 Members of the Halifax Department responded quickly, 1001 00:48:14,120 --> 00:48:16,430 and were positioning their engine up to the nearest 1002 00:48:16,430 --> 00:48:19,440 hydrant when the Mont-Blanc disintegrated in a blinding 1003 00:48:19,440 --> 00:48:22,340 white flash, creating the biggest man-made explosion 1004 00:48:22,340 --> 00:48:24,970 before the nuclear age." It was 9:05 a.m. 1005 00:48:24,970 --> 00:48:26,330 on a Thursday morning. 1006 00:48:26,330 --> 00:48:29,260 "Over 1,900 people were killed immediately. 1007 00:48:29,260 --> 00:48:31,460 Within a year, the figure climbed to well over 2,000. 1008 00:48:31,460 --> 00:48:33,490 Around 9,000 were injured, many permanently. 1009 00:48:33,490 --> 00:48:38,280 325 acres, almost all of North End Halifax was destroyed. 1010 00:48:38,280 --> 00:48:40,230 Much of what was not immediately leveled burned to 1011 00:48:40,230 --> 00:48:43,850 the ground, aided by what are stockpiles of coal in cellars. 1012 00:48:43,850 --> 00:48:46,630 As for the Mont-Blanc, all 3,000 tons of her were 1013 00:48:46,630 --> 00:48:49,040 shattered into little pieces that were 1014 00:48:49,040 --> 00:48:50,580 blasted far and wide. 1015 00:48:50,580 --> 00:48:52,530 The barrel of one of her cannons landed three and a 1016 00:48:52,530 --> 00:48:53,850 half miles away. 1017 00:48:53,850 --> 00:48:56,810 Part of her anchor shank, weighing half a ton, flew two 1018 00:48:56,810 --> 00:48:58,800 miles in the opposite direction. 1019 00:48:58,800 --> 00:49:02,730 Windows shattered 50 miles away, and the shock wave was 1020 00:49:02,730 --> 00:49:06,300 felt even in Sydney, on Cape Breton Island, 270 miles to 1021 00:49:06,300 --> 00:49:07,470 the northeast. 1022 00:49:07,470 --> 00:49:09,030 "There was about 20 minutes between the 1023 00:49:09,030 --> 00:49:11,180 collision and the explosion. 1024 00:49:11,180 --> 00:49:13,450 It was enough time for spectators, including many 1025 00:49:13,450 --> 00:49:16,600 children, to run to the waterfront to watch the ship 1026 00:49:16,600 --> 00:49:18,750 burning, thus coming into close range." 1027 00:49:18,750 --> 00:49:21,160 I mean, they were little kids, and it's a fire, and the fire 1028 00:49:21,160 --> 00:49:23,020 engines are coming! 1029 00:49:23,020 --> 00:49:26,010 It's fun! 1030 00:49:26,010 --> 00:49:29,585 It's more interesting than going to school, right? 1031 00:49:29,585 --> 00:49:33,010 "It was enough time for others to gather at windows. 1032 00:49:33,010 --> 00:49:35,880 Office workers came to the windows, and with the 1033 00:49:35,880 --> 00:49:40,380 explosion, the glass shattered and blinded them. 1034 00:49:40,380 --> 00:49:42,630 "Not surprisingly, the hospitals weren't able to cope 1035 00:49:42,630 --> 00:49:44,040 with so many wounded. 1036 00:49:44,040 --> 00:49:45,950 There was also a desperate need for housing, and the 1037 00:49:45,950 --> 00:49:47,150 misery was compounded"-- 1038 00:49:47,150 --> 00:49:48,190 are you ready for this?-- 1039 00:49:48,190 --> 00:49:50,810 "by the blizzard that struck the city the following day, 1040 00:49:50,810 --> 00:49:55,340 dumping 16 inches of snow over the ruins. 1041 00:49:55,340 --> 00:49:58,270 "With astounding speed, relief efforts were set in motion. 1042 00:49:58,270 --> 00:50:01,210 Money poured in from as far away as China and New Zealand, 1043 00:50:01,210 --> 00:50:02,840 Canadian Government gave--" blah, blah, blah. 1044 00:50:02,840 --> 00:50:04,310 "But most Haligonians"-- 1045 00:50:04,310 --> 00:50:07,630 which is what you call a denizen of Halifax-- 1046 00:50:07,630 --> 00:50:10,620 "most Haligonians remember the generosity of the state of 1047 00:50:10,620 --> 00:50:15,860 Massachusetts, which donated $750,000 of money and goods, 1048 00:50:15,860 --> 00:50:18,470 and gave unstintingly in volunteer assistance through 1049 00:50:18,470 --> 00:50:21,440 the Massachusetts Halifax Relief Committee." 1050 00:50:21,440 --> 00:50:23,810 People from the hospital district here got on trains, 1051 00:50:23,810 --> 00:50:26,740 and went up there to assist, especially from Mass Eye and 1052 00:50:26,740 --> 00:50:29,920 Ear, to assist the people that had been blinded. 1053 00:50:29,920 --> 00:50:34,320 "Starting in 1971, to this day, Halifax sends an annual 1054 00:50:34,320 --> 00:50:38,930 Christmas tree to the city of Boston in gratitude." 1055 00:50:38,930 --> 00:50:43,390 And there are specifications on what the tree should look 1056 00:50:43,390 --> 00:50:46,170 like, and how big it should be, and so on, and they bring 1057 00:50:46,170 --> 00:50:48,070 it over to Boston Commons. 1058 00:50:48,070 --> 00:50:52,490 So if, in the days that come, when you get back from 1059 00:50:52,490 --> 00:50:54,820 Thanksgiving, if you happen to be across the river and you 1060 00:50:54,820 --> 00:50:58,020 see something that's about 45 feet high and it looks like it 1061 00:50:58,020 --> 00:51:01,960 came from Canada, this is what it is. 1062 00:51:01,960 --> 00:51:05,780 And it's all about the Halifax explosion. 1063 00:51:05,780 --> 00:51:06,090 OK. 1064 00:51:06,090 --> 00:51:07,120 There you go. 1065 00:51:07,120 --> 00:51:07,430 All right. 1066 00:51:07,430 --> 00:51:08,460 Well, have a nice weekend. 1067 00:51:08,460 --> 00:51:10,600 We'll see you on Monday.