00:01 Now, let's bring on the role of water. 00:04 Any system will adopt the lowest energy configuration. 00:08 This is to do with enthalpy and it's also to do with entropy. 00:13 In chemical systems, this means that the participant will form as many bonds as possible of the strongest type. 00:19 The more bonds it can form of the strongest type, the more stable that system will be. 00:24 For example, if we look at water molecules hydrogen bonding with each other, let's say in ice, each molecule can make it possible for hydrogen bonds. 00:34 In liquid water, however, hydrogen bonds are continuously forming and breaking. 00:40 On average, each molecule makes around 3.4 hydrogen bonds. 00:46 So, let's have a look and see what that is. 00:49 If you look at the hydrogen-bonded cluster on the left-hand side, you can see that this is where the average is derived from. 00:56 At any one time, there will be highly bonded hydrogen-bonded clusters, ice-like ones, and areas with very few hydrogen-bonded clusters. 01:06 And therefore, you can see we have free molecules there. 01:10 Now, let's have a look at what this means in terms of ion solvation. 01:16 This doesn't just relate to the solvation of ion such as those we discussed in Module Two, but also indeed any charged species, be it organic or inorganic. 01:25 When water dissolves and solvates other polar molecules, remember, like dissolves like, a shell of water is formed around the polar molecules, which prevents them from interacting with each other. 01:37 This enables the water and also the drug to achieve its lowest energy configuration. 01:43 Now, let's have a look at solvent effects. Life on Earth uses water as a solvent, which is good in many respects as it dissolves polar drugs, and also biomolecules such as proteins and DNA will also dissolve. 01:59 However, the bad point between this is that interactions between the molecules are weakened as a result of the water effectively getting in the way. 02:08 To understand how this problem is overcome, we must first consider the interactions of nonpolar molecules in water. 02:15 And that's what we're gonna do in the diagram on the next slide. 02:18 So, let's consider a drop of oil and water. 02:22 I'm sure you've all done this, either by accident or by design. 02:25 Vegetable oil and water doesn't -- actually, is not miscible, it is immiscible. 02:30 And therefore, it exists as an emulsion. 02:33 When you have a small amount, it exists as a drop, usually forming on the surface. 02:38 The oil in this case is represented by the yellowy orange circle, and the water, obviously, in blue. 02:44 So, as we add a drop of water to the system -- of oil to the system, what happens is that the water itself cannot hydrogen bond with the oil. 02:52 So, whereas with, let's say for the sake of argument, ethanol, is equally dispersed throughout the water, because hydrogen bonding is possible between alcohol and water. 03:02 In the case of an oil, it tends to preferentially bind to itself. 03:07 Now, ostensibly, you may think this is odd. 03:09 Why would something not bind to itself when there are hydrogen bonds available to it? The point is that fats themselves are highly lipophilic. 03:17 They're not capable of bonding in a hydrogen bonding fashion they are only capable of bonding in a Van der Waals fashion. 03:24 And as we've said, Van der Waals forces are very, very weak. 03:28 And so, that which holds them together is only the Van der Waals. 03:31 And what happens is the water tries to adopt the best possible configuration around this oil droplet, forming a water cage. 03:40 Okay, so let's consider the thermodynamics in this system. 03:44 The energy of the system as a whole goes up because there are fewer hydrogen bonds, and as a consequence, disorder decreases. 03:53 I refer you to the Gibbs free energy equation, which you can look up. 03:57 Entropy decreases when you have a more ordered system. 04:02 Entropy increases when you have greater disorder. 04:06 Now, let us consider two oil drops. 04:09 They will sit in two water cages, so the energy in the system is even higher. 04:15 The energy can be decreased by merging the drops into a larger one, and doing so releases some of the ordered molecules back into solution. 04:25 The water squeezes the nonpolar molecules together, but they do not have a strong affinity for each other, but this is the thing I want to get back to, water does for itself, being capable as we know, of hydrogen bonding to itself. 04:40 So, let's see what this means in terms of a drug and a potential receptor. 04:44 We have here the drug shown on the left hand-side in red. 04:47 Around it, we have ordered water molecules, regions of structured water. 04:53 As the structure of water is displaced from the binding side and also from the region of which the drug binds. 05:01 So, this actually results in a decrease in energy when you're dealing with something which is lipophilic as a receptor, and also relatively lipophilic as a drug. 05:11 So, this obviously decreases the energy available to it.
The lecture Role of Water – Biological Interactions by Adam Le Gresley, PhD is from the course Medical Chemistry.
What happens when a polar compound is dissolved in water?
Complete the following statement. The stability of a system is ...
With an increase in the entropy of the system, the system does what?
What happens when a lipophilic drug interacts with a lipophilic receptor?
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