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Skip to 0 minutes and 11 seconds SPEAKER 1: So far, we’ve drawn our molecules in two dimensions. What we need to do now is consider their three-dimensional shapes. Considering our gas, butane, each of the carbon atoms in butane makes four bonds. These are oriented in a tetrahedral manner. And this movie shows us a 3D depiction of butane as we rotate it around, where we can see that each carbon atom is attached to four other atoms. The number of bonds an atom makes dictates the shape of that molecule. But on top of this, we also have to consider flexibility.

Skip to 0 minutes and 53 seconds Using these tetrahedral linkages, we could also construct rings. On the left, we have piperidine, a six-membered ring with five carbons and a nitrogen atom. The molecule adopts a shape that is dictated by the characteristics of each atom. Benzene, on the other hand, is very flat. And we can see this having rotated the structure by 90 degrees. Nicotine combines two types of ring structures, and we can now introduce the concept that most molecules can adopt different shapes. In other words, they are flexible. The bond we’ve highlighted here allows the rotation of one ring relative to the other. In this movie, we can see that nicotine can assume different shapes as the rings move relative to each other.

Skip to 1 minute and 46 seconds However, not all of these shapes are favoured, as molecules need to obey certain energy rules. As atoms tend to avoid bumping into each other, this will favour certain orientations of the rings. This is one of those favoured orientations.

Skip to 2 minutes and 7 seconds In nature, chemicals interact with each other and with other substances in their environment. This might involve the simple attraction of a positive to a negative charge. Likewise, hydrophobic groups can be attracted to each other. For this course, we need to consider how our drugs interact with proteins to exert their biological effect. For simplicity, we will outline three types of interactions that take place between our medicines and their protein targets.

Skip to 2 minutes and 42 seconds Salt bridges occur between two charged groups. And a good example is the interaction between negatively charged carboxylic acids and positively charged amino groups. These bonds, which are electrostatic in nature, are usually strong and contribute to a drug’s potency. Next up, we have hydrogen bonds, which mostly occur between groups with nitrogen and oxygen atoms and their associated hydrogen atoms. These two are electrostatic in nature but don’t involve the full challenges we see in salt bridges. As such, they are less strong than a salt bridge. Importantly, hydrogen bonds are used by drug designers to provide specificity for the different protein targets. And finally, there are hydrophobic interactions. Hydrophobic groups are those which a chemist might describe as being greasy.

Skip to 3 minutes and 39 seconds These interactions occur between hydrophobic parts of the molecule and hydrophobic sections of the protein. In this case, these groups are able to interact together and avoid water. While these interactions in isolation are weak, indicated by the wavy lines, they play a significant role in drug protein binding, particularly when there’s a good fit between the shape of the drug and the shape of the binding site. So let’s recap what we’ve covered in this chemistry introduction. We’ve talked about the usual chemical elements that we see in drugs and shown you some simple chemical structures. This meant we had to talk about the bonds between atoms and how we draw molecules.

Skip to 4 minutes and 26 seconds All drugs have important functional groups, which are important for binding to proteins. We also had to consider the shape of molecules and their flexibility. Finally, we touched on three important interactions that occur between drugs and their protein binding sites.

Introduction: chemistry part 2

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The Science of Medicines

Monash University

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