Role of Water – Biological Interactions

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.