thermodynamics Flashcards
Thermodynamics (TDs)
deals with the quantitative relationships of interconversion of various forms of energy - including mechanical, chemical, electrical, and radiant.
TDs is not concerned with dynamics; rather it deals with the equilibrium positions of systems, in which there is no further tendency to change.
TDs makes no assumptions about the molecules comprising a system but enables relations between macroscopic measurable properties (e.g., temperature, volume, solubility) to be derived
energy
Energy is a property that determines the fate of simple chemical processes
and the very complex behaviour of biological cells
In chemical reactions, energy determines what reaction may occur, how fast it may proceed and in which direction.
Energy has several forms, including:
- kinetic, as a result of a body’s or a molecule’s motion
- potential, due to its position
- coulombic or electrostatic, associated with charged particles
All forms of energy are related but their inter-conversion cannot create or destroy energy.
Chemical Thermodynamics – why do we care?
Partitioning of drugs between (e.g.) membranes and aqueous fluids
Drug solubility and diffusion
Micellization of surface-active compounds; hydrophobic effect
Drug-receptor interactions
Phase transitions
1st Law of thermodynamics
Statement of the conservation of energy – although energy can be transformed from one kind to another, it cannot be created or destroyed
lost potential energy is converted in to friction
2nd Law of thermodynamics
Entropy of an isolated system increases in a spontaneous change – the 2nd Law is concerned with the probability of a process occurring based on the observed tendency of a system to approach energy equilibrium… heat does not flow spontaneously from a cold to a hot body!
3rd Law of thermodynamics
Entropy of a pure, crystalline substance equals zero at a temperature of absolute zero (0 K) because the crystal arrangement must then have the greatest possible orderliness
Internal energy (U) of a system
sum of all kinetic and potential energy contributions from all the atoms/ions/molecules present
In TDs, we are interested in changes in internal energy (ΔU), not the absolute value.
Internal energy of a closed system can be changed in only 2 ways:
- by transferring energy as work, w
- by transferring energy as heat, q
- hence: ΔU = w + q
Enthalpy
Consider a change occurring in a system at constant pressure; e.g., a chemical reaction in an open vessel.
In this case, ΔU ≠ energy supplied as heat because some is lost by work done against the atmosphere during expansion of the system
It is then convenient to define a property, called enthalpy, = heat supplied at
constant pressure (P) and U = H + PV.
- hence, we define: ΔH = q at constant pressure
- ΔH is positive when heat is supplied to system, which is free to change its volume
- ΔH is negative when the system releases heat (as in an exothermic reaction)
Enthalpy changes occur in important pharmaceutical processes, such as: dissolution of a drug, micelle formation, chemical reaction (e.g., metabolism, degradation), adsorption onto surfaces, solvent evaporation, hydration of drugs/excipients (stability), acid/base neutralization, melting/freezing of solutes
Entropy
Measure of randomness or disorder of a system is the entropy.
More ‘chaos’ means increased entropy and greater degree of disorder
1st Law of TDs demands conservation of energy but says nothing about which changes occur spontaneously.
Changes with a natural tendency to occur are not because the system is moving to a lower energy state.
Rather, spontaneous changes take place because there are changes in the randomness of the system.
2nd Law of TDs: entropy of an isolated system increases in a spontaneous change
The entropy of a substance changes when it undergoes a phase transition, as this leads to a change in order.
For example, when a crystalline drug melts, it changes from an organised lattice to a more chaotic liquid.
Entropy therefore increases and ΔS = ΔHfus/T, where ΔHfus is the enthalpy of fusion (melting) and T = m.pt.
At absolute zero, all thermal motions of atoms in a crystal lattice cease and the solid has no disorder, i.e., zero entropy; ➠ 3rd Law of TDs: entropy of a perfectly crystalline material is zero when T = 0 K.
Free energy
Free energy (Gibbs free energy, G) is derived from entropy.
ΔG at constant temperature arises from changes in enthalpy and entropy: ΔG = ΔH – TΔS
At constant temperature and pressure, therefore: ΔG = -TΔS (and is another way of expressing ΔS)
⇒ ΔG will decrease in a spontaneous process
ΔG will continue to decrease until the system reaches equilibrium and ΔG = 0
When the system attains equilibrium, it cannot reverse itself
⇒ All spontaneous processes are irreversible
Partitioning, chemical potential (TD activity), membrane transport and drug delivery
A drug’s partition coefficient (K) between oil and water is measured in an experiment (opposite) and, at equilibrium: K = Coil/Cwater
K = drug’s relative affinity for oil as compared to water.
K is rarely equal to 1 and can be»_space;1 or «1, meaning that Coil and Cwater, at equilibrium, can be very different
Put another way, the drug’s chemical potential in oil and in water is the same.
degree of saturation = leaving tendency
Obviously, the leaving tendency is maximised (and equal to 1) when: Coil = Soil or Cwater = Swater
Therefore, to drive drug absorption across a membrane, which acts as a barrier to reaching its target, the closer the concentration in the formulation is to Sformulation, the better the rate of delivery.
A practical example is a transdermal patch.
in the adhesive polymer layer, the drug is present typically at close to its solubility in that material.
This ensures that drug is delivered at close to its maximum flux possible across the skin, thereby keeping the area of the patch to a reasonable size.
Diffusion - Fick’s 1st law
A system not in equilibrium moves towards equilibrium.
To do so, flow must occur.
“The flux, at any point in the system, is proportional to the potential energy gradient” [e.g., a chemical potential gradient or a temperature gradient].
The further a system from equilibrium, the faster it moves towards equilibrium.
When a concentration gradient is present, free energy is minimized when mixing is uniform (entropy is maximized)… ΔG = ΔH – T.ΔS
Driving force towards equilibrium is the concentration gradient (c/x)
Hence, flow ceases when (c/x) = 0, i.e., uniform concentration
Thermodynamics of protein binding
Negative ΔG values ⇒ binding is spontaneous
Negative ΔH values ⇒ exothermic reaction
Positive ΔS values ⇒ loss of structured H2O on binding
Micellization
SLS is a surfactant, or a surface-active agent.
SLS has a polar, hydrophilic head-group (the sulphate) and a non-polar, hydrophobic ‘tail’ (the hydrocarbon chain).
When added to water, SLS molecules preferentially populate the surface (‘hydrophobic effect’) until it is full.
Addition of more SLS eventually leads to ‘micellization’ whereby surfactant molecules self-assemble.
SLS concentration at which micellization occurs is the critical micelle concentration (CMC).
CMC decreases with increasing hydrocarbon chain length; CMC increases as head group becomes more polar.
At the CMC, micellization occurs spontaneously and is primarily entropy-driven.
Surfactants have wide use in pharmaceutical sciences (stabilisers, emulsifiers, solubilisation, etc.).
Surfactant physical properties depend sensitively on concentration and on the CMC
e.g., acting as a detergent, affecting surface tension
Discontinuity in many physical properties observed at the CMC.
