1 00:00:02,639 --> 00:00:06,970 Have you ever wondered why the word Ambulance is printed as its mirror image on the front 2 00:00:06,970 --> 00:00:12,039 an Ambulance truck? The word is written this way so that drivers can read the word in their 3 00:00:12,039 --> 00:00:18,710 rearview mirror signaling them to pull over if necessary. In chemistry and biology, molecules 4 00:00:18,710 --> 00:00:24,800 can also be mirror image of each other and have very different functions. 5 00:00:24,800 --> 00:00:31,739 This video is part of the Structure-Function-Properties video series. The structure, function and 6 00:00:31,739 --> 00:00:38,739 properties of a system are related and depend on the processes that define or create the 7 00:00:38,780 --> 00:00:39,859 system. 8 00:00:39,859 --> 00:00:46,629 Hi, my name is Brad Pentelute, and I am a professor of chemistry at MIT. My research 9 00:00:46,629 --> 00:00:52,449 focuses on the biological properties of mirror-image proteins and how these macromolecules may 10 00:00:52,449 --> 00:00:57,179 be used in pharmaceutical applications and therapeutics. 11 00:00:57,179 --> 00:01:02,179 Before watching this video, you should be familiar with: Molecular Geometry, the structure 12 00:01:02,179 --> 00:01:07,689 of the 20 naturally occurring amino acids, as well as have an understanding of what a 13 00:01:07,689 --> 00:01:11,729 protein is and its three-dimensional structure 14 00:01:11,729 --> 00:01:14,700 After watching this video, you will be able to: 15 00:01:14,700 --> 00:01:19,549 Identify chiral objects and molecules Understand how chirality plays a role in the 16 00:01:19,549 --> 00:01:26,549 function of biological compounds. 17 00:01:27,520 --> 00:01:32,469 Let's begin by talking about chirality. In this video, you'll see that chirality is an 18 00:01:32,469 --> 00:01:37,770 important feature in biological molecules because molecular structure is often closely 19 00:01:37,770 --> 00:01:40,780 related to biological function. 20 00:01:40,780 --> 00:01:47,780 A molecule is chiral if it is not superimposable with its mirror image. But, before we talk 21 00:01:55,060 --> 00:02:02,060 about chirality in molecules, let's first look at a couple of ordinary objects to learn 22 00:02:30,489 --> 00:02:34,480 exactly what we mean by the term, chirality. 23 00:02:34,480 --> 00:02:39,390 Let's look at a common example of chirality in this left and right glove. Gloves are mirror 24 00:02:39,390 --> 00:02:44,510 images of one another. The gloves look identical but we know from experience that they are 25 00:02:44,510 --> 00:02:50,150 not the same. They have different shapes. One fits only your left hand and the other 26 00:02:50,150 --> 00:02:56,579 fits only your right hand. If we try to lay the right glove on top of the left glove and 27 00:02:56,579 --> 00:03:02,450 align their key features, we see that they are not superimposable at all. Because left 28 00:03:02,450 --> 00:03:07,980 and right gloves are non-superimposable mirror images, we can say that gloves are chiral. 29 00:03:07,980 --> 00:03:13,480 Are there other objects that you can think of that are chiral? Please pause the video 30 00:03:13,480 --> 00:03:20,480 here to think of a few examples. 31 00:03:22,390 --> 00:03:27,319 You may have suggested such objects as your left or right ears, a drinking fountain, or 32 00:03:27,319 --> 00:03:29,900 a screw. 33 00:03:29,900 --> 00:03:34,180 Let's look at this airplane. Is it chiral? If we take the airplane and compare it to 34 00:03:34,180 --> 00:03:40,640 its mirror image, we can see that the two images are identical and are superimposable. 35 00:03:40,640 --> 00:03:46,180 Therefore, the airplane is not chiral. Can you describe what characteristic of the airplane 36 00:03:46,180 --> 00:03:53,180 makes it achiral? Please pause the video and give a possible answer. 37 00:03:57,340 --> 00:04:01,900 There is a plane of symmetry through the center of the airplane itself. If one half of an 38 00:04:01,900 --> 00:04:08,150 object can be reflected onto its other half, then the object is never chiral. Can you think 39 00:04:08,150 --> 00:04:13,260 of another object with an internal plane of symmetry? Please pause the video and try to 40 00:04:13,260 --> 00:04:20,260 think of other achiral objects and where the internal plane of symmetry would be. 41 00:04:24,880 --> 00:04:30,630 Objects such as a chair, a drinking glass, and a fork have an internal plane of symmetry 42 00:04:30,630 --> 00:04:37,630 and hence are achiral. The planes of symmetry are here, here, and here. 43 00:04:38,720 --> 00:04:43,850 Notice that there is no way to divide a right-handed glove into two equal halves, which is why 44 00:04:43,850 --> 00:04:45,690 the glove is chiral. 45 00:04:45,690 --> 00:04:52,690 Finally, another everyday object that I want to show you is this fan. First, let's think. 46 00:04:52,700 --> 00:04:59,700 Do you think a fan is chiral? Please pause the video and discuss this with a friend. 47 00:05:04,860 --> 00:05:11,860 Is the fan chiral? Yes, it is. Each blade is hung with a tilt that makes the fan chiral! 48 00:05:11,860 --> 00:05:16,510 The function of the tilted blades pushes air forward to create a wind chill effect to cool 49 00:05:16,510 --> 00:05:22,540 you. However, the tilted blades also cause the fan to be non-superimposable with its 50 00:05:22,540 --> 00:05:29,540 mirror image. As you can see, the mirror image has blades that tilt in the opposite direction. 51 00:05:29,670 --> 00:05:36,670 All objects can be classified as chiral or achiral, including molecules. 52 00:05:38,909 --> 00:05:44,550 As with objects, a molecule is chiral if it is non-superimposable with its mirror image. 53 00:05:44,550 --> 00:05:51,550 The mirror image of a chiral molecule is called its enantiomer. Enantio is Greek for opposite 54 00:05:52,240 --> 00:05:56,490 and the term enantiomer describes the relationship between the two molecules. 55 00:05:56,490 --> 00:05:57,190 Enantiomers have identical molecular formulas and have the same chemical connectivity but 56 00:05:57,190 --> 00:05:57,880 differ in the three-dimensional spatial arrangement of the atoms in the molecule. 57 00:05:57,880 --> 00:06:03,400 Let's look at this model of the molecule, bromo-chloro-iodo methane. The green ball 58 00:06:03,400 --> 00:06:08,770 represents a chlorine atom, the orange ball represents a bromine atom, the purple ball 59 00:06:08,770 --> 00:06:14,660 represents an iodine atom and the white ball represents a hydrogen atom. 60 00:06:14,660 --> 00:06:19,870 If we take our molecule and hold it in front of a mirror, we see the molecule and its image 61 00:06:19,870 --> 00:06:25,810 in the mirror. But, now let's look at 3-D models of both our original molecule and its 62 00:06:25,810 --> 00:06:31,900 mirror image. We see that the two are not superimposable, regardless of how one rotates 63 00:06:31,900 --> 00:06:38,900 the molecules. Hence, this tells us that bromo-chloro-iodo methane is a chiral molecule. 64 00:06:50,880 --> 00:06:56,440 A quick way to know if a molecule is chiral is to check and see if it has a chiral center. 65 00:06:56,440 --> 00:07:02,910 A chiral center is a tetrahedral atom attached to four different atoms or groups. The tetrahedral 66 00:07:02,910 --> 00:07:06,040 atom is usually carbon. 67 00:07:06,040 --> 00:07:12,690 Let's make a model of the organic compound, 2-chlorobutane. The number 2 in front of the 68 00:07:12,690 --> 00:07:18,060 compound name means that chlorine is on the second carbon atom. This carbon is attached 69 00:07:18,060 --> 00:07:24,030 to four different groups, chlorine, hydrogen, a -CH3 group and a -CH2CH3 group and that 70 00:07:24,030 --> 00:07:28,770 means that it's a chiral center. What would happen to the chirality of this 71 00:07:28,770 --> 00:07:33,990 compound if we substituted the hydrogen atom with a second chlorine atom? Would the resulting 72 00:07:33,990 --> 00:07:40,990 molecule be chiral? Please pause the video here. 73 00:07:44,930 --> 00:07:51,360 This new molecule, called 2, 2 di-chlorobutane is not chiral. The second carbon with two 74 00:07:51,360 --> 00:07:57,080 chlorine atoms no longer has four different groups attached. You can even see that this 75 00:07:57,080 --> 00:08:02,630 molecule has an internal plane of symmetry and therefore can be superimposable on its 76 00:08:02,630 --> 00:08:09,630 mirror image. When we do have a chiral molecule, sometimes 77 00:08:10,630 --> 00:08:16,850 its enantiomer has an entirely different function. For example, the enantiomers of Carvone are 78 00:08:16,850 --> 00:08:22,300 the flavors of caraway and spearmint. One enantiomer of Carvone fits into a specific 79 00:08:22,300 --> 00:08:27,890 receptor in your nose only in the way a left-handed glove fits your left hand. The other enantiomer 80 00:08:27,890 --> 00:08:32,570 of carvone fits into an entirely different receptor, resulting in the different odor.Many 81 00:08:32,570 --> 00:08:33,890 drugs such as the pain reliever, ibuprofen has biological activity while its enantiomer 82 00:08:33,890 --> 00:08:38,659 As with simple molecules, it is possible for proteins to exist that are mirror images of 83 00:08:38,659 --> 00:08:44,660 each other. However, this doesn't occur in nature. Naturally occurring proteins are composed 84 00:08:44,660 --> 00:08:51,660 of L-amino acids only. It is not clear why nature selected for this particular enantiomer. 85 00:08:51,660 --> 00:08:56,060 Selection of L-amino acids has structural consequences for a proteins three-dimensional 86 00:08:56,060 --> 00:08:57,490 shape. 87 00:08:57,490 --> 00:09:02,240 Pause the video here and discuss with a friend the general structure of amino acids. What 88 00:09:02,240 --> 00:09:09,240 are the groups attached to the central carbon? Which if any of the amino acids are achiral? 89 00:09:12,220 --> 00:09:17,890 An amino acid contains both an amino group and a carboxylic acid group. It also contains 90 00:09:17,890 --> 00:09:24,890 a hydrogen atom and a sidechain. The central atom is carbon. Of the 20 naturally occurring 91 00:09:24,940 --> 00:09:31,940 amino acids, glycine is the only achiral amino acid. Its sidechain is a second hydrogen atom. 92 00:09:33,250 --> 00:09:38,720 The remaining 19 amino acids have the L configuration. 93 00:09:38,720 --> 00:09:43,350 Let us recall that naturally occurring amino acids have an L-configuration and combine 94 00:09:43,350 --> 00:09:49,000 to form L-proteins. However, scientists can now chemically synthesize proteins made up 95 00:09:49,000 --> 00:09:55,090 entirely of D-amino acids. These synthetic macromolecules are also known as D-proteins. 96 00:09:55,090 --> 00:10:00,960 Interestingly, these proteins fold into three- dimensional structures, which mirror those 97 00:10:00,960 --> 00:10:07,960 of the naturally occurring L-protein counter-part. 98 00:10:10,500 --> 00:10:15,000 Snow fleas are a species of dark blue insect. They are often seen bouncing around on the 99 00:10:15,000 --> 00:10:20,860 snow in the winter. Ice fish live in the Antarctic. These fish live in the ocean at subzero temperatures. 100 00:10:20,860 --> 00:10:26,940 What do the snow flea and the arctic fish have in common? They can both survive in subfreezing 101 00:10:26,940 --> 00:10:32,840 temperatures. How do they do this? Both creatures make a class of proteins called Antifreeze 102 00:10:32,840 --> 00:10:39,570 proteins. These proteins protect these organisms and others, including moths, beetles, plants 103 00:10:39,570 --> 00:10:44,930 and even bacteria by binding to water and stopping the growth of ice crystals in their 104 00:10:44,930 --> 00:10:49,340 bodies. Is water chiral? Please pause the video here 105 00:10:49,340 --> 00:10:56,340 and try to answer this question. 106 00:10:57,300 --> 00:11:02,000 Here you can see the chemical structure of water. As you can see, it has two planes of 107 00:11:02,000 --> 00:11:09,000 symmetry, and water is superimposable with its own mirror image. 108 00:11:09,250 --> 00:11:16,230 The antifreeze protein is comprised of 81 amino acids folded into six helices. Each 109 00:11:16,230 --> 00:11:22,290 helix is connected by amino acids that form a short connecting loop. The helices in the 110 00:11:22,290 --> 00:11:27,830 antifreeze protein are left-handed. Do you think the helices are chiral? Pause the video 111 00:11:27,830 --> 00:11:34,830 and discuss this with a friend. 112 00:11:36,370 --> 00:11:40,460 The helix winds up in the direction of your left thumb when your fingers are curled in 113 00:11:40,460 --> 00:11:46,360 to make a fist. These helices do not have an internal plane of symmetry, and are not 114 00:11:46,360 --> 00:11:51,290 superimposable with their mirror images. They are chiral. 115 00:11:51,290 --> 00:11:58,290 The antifreeze protein was the first protein whose mirror image was chemically synthesized. 116 00:11:58,650 --> 00:12:04,930 The mirror image protein is composed of entirely D-amino acids. The helices are right-handed, 117 00:12:04,930 --> 00:12:09,870 opposite to that of the naturally occurring protein. They wind up in the direction of 118 00:12:09,870 --> 00:12:16,460 your right thumb when your fingers are curled in to make a fist. In proteins, we see chirality 119 00:12:16,460 --> 00:12:21,300 in the amino acid units and in the secondary structure as well. 120 00:12:21,300 --> 00:12:25,420 Do you think the D-form of the antifreeze protein will have a function the same as or 121 00:12:25,420 --> 00:12:32,420 different from the natural L-form? Please pause the video here and discuss with a friend. 122 00:12:34,920 --> 00:12:41,920 Interestingly, the mirror image protein has the same antifreeze properties. This is because 123 00:12:44,060 --> 00:12:51,060 its binding partner, water is achiral. So the mirror image protein can still bind water. 124 00:12:54,170 --> 00:12:59,240 Hopefully by now you have the tools to recognize chiral objects and molecules, and the role 125 00:12:59,240 --> 00:13:05,610 that chirality can play in recognition and specificity between biological systems. In 126 00:13:05,610 --> 00:13:11,590 this video, we saw that an object or molecule is chiral if it cannot be superimposed onto 127 00:13:11,590 --> 00:13:18,190 its mirror image. Objects or molecules that have an internal plane of symmetry are never 128 00:13:18,190 --> 00:13:24,750 chiral. We also talked about enantiomers, which are the mirror image of a chiral molecule. 129 00:13:24,750 --> 00:13:30,620 Since the spatial orientation of the atoms in enantiomers are different, chiral compounds 130 00:13:30,620 --> 00:13:35,430 can and often do have distinct functions. But, as you saw with the antifreeze protein, 131 00:13:35,430 --> 00:13:37,710 sometimes there are exceptions to the rule!