Lectures 5 and 6 - Thermodynamics PDF

Fundamentals of Pharmacy / Pharmacology: The Science of Medicines LS12102 / LS12011 Thermodynamics Professor Duncan Craig [email protected]  CONTENTS Introduction to thermodynamics – why do pharmaceutical scientists need to know about this subject? Hea...

Fundamentals of Pharmacy / Pharmacology: The Science of Medicines LS12102 / LS12011 Thermodynamics Professor Duncan Craig [email protected]  CONTENTS Introduction to thermodynamics – why do pharmaceutical scientists need to know about this subject? Heat, temperature, energy and work The three laws of thermodynamics Thermodynamics in the pharmaceutical sciences  LEARNING OBJECTIVES By the end of this lecture course/workshops you should be able to Understand and manipulate the basic concepts of thermodynamics to understand real life situations Appreciate how thermodynamics informs the pharmaceutical sciences MORE INVALUABLE KNOWLEDGE AND UNDERSTANDING You will also learn Why it is a pain to tidy your room Why you burn your feet on sand on the way to the sea Why ice cream melts slowly Why you never seem to have any money These important concepts will be explored in the workshops  REFERENCE SOURCES Reading list “Physicochemical Principles of Pharmacy”; A.T. Florence & D.Attwood (3rd edition) MacMillan Press, London, 1998; chapter 3 “Martin’s Physical Pharmacy and Pharmaceutical Sciences”; P.J. Sinko, editor (6th edition) Lippincott, Williams & Wilkins, Baltimore, 2011, chapter 3 “Basic Chemical Thermodynamics”; E.B. Smith (2nd edition) Oxford University Press, Oxford, 1979  INTRODUCTION TO THERMODYNAMICS Basic Drug Drug Medicines Patient benefit science discovery disposition development Thermodynamics is an essential component of the toolbox of any scientist It also enables us to understand how drugs act on receptors, how they are distributed around the body and how we can formulate them into medicines  WHAT IS THERMODYNAMICS? Thermodynamics - the science of energy transfer Energy is the ability to perform work (see later) Generally applicable but molecularly non- specific Kinetic energy The energy of moving objects or mass Will tell you whether a reaction or process (e.g. mechanical energy) will take place but not how fast Potential energy The study of the rates associated with a Energy that is stored (e.g. nuclear reaction or process is kinetics energy)  HEAT, TEMPERATURE AND WORK What is heat and how do we measure it? Initially believed to be a physical substance (caloric), then considered to be ‘motion itself’ Now know that heat is a form of energy caused by molecular motion Heat is also considered in terms of thermal energy transfer between objects (e.g. hot water)  Temperature describes the propensity for heat to flow from one body to another Initially sensory Newton (circa 1700) developed scale (0 to 12) between water freezing and body temperature Fahrenheit (1724) – used freezing of a salt solution and body temperature with 96 divisions between the two  This led to well accepted Fahrenheit scale with 32o being melting point of ice, 98.6o being body temperature and 212o being the boiling point of water Celsius (1742) assigned freezing point of water as 0oC and the boiling point as 100oC Body temperature is 37oC For accurate work the thermodynamic temperature scale is used Zero of this scale is the zero of molecular motion (see later) Measured in Kelvins (K) whereby 0oC = 273.15K  THE CONCEPT OF WORK Work represents the transfer of energy in an ordered fashion, heat is random molecular motions Work defined by energy barrier it overcomes Both work and heat are forms of energy and are thus expressed in Joules (J) Total internal energy of Heat and work are the two system (U) ways in which energy can be added or subtracted from a system Work (W) Heat (Q) What do we mean by system? MATTER Isolated ENERGY system MATTER Closed system ENERGY MATTER Open system ENERGY An example of the interchange between heat and work Give us a sign………..  1ST LAW OF THERMODYNAMICS The algebraic sum of all energy changes in an isolated system is zero (Energy cannot be created or destroyed but merely transferred) Seven main forms of energy - electrical, gravitational, chemical, radiation, thermal, mechanical, nuclear Electrical to mechanical (motors) Gravitational to mechanical (falling weight) Thermal to radiation (lightbulb) Nuclear to thermal (atomic fission)  THE CONCEPT OF ENTHALPY The key events we are concerned with in the pharmaceutical sciences are reactions – physical or chemical These are dominated by changes in heat energy The heat energy change within a system is expressed as enthalpy (H) – expressed as a change value rather than an absolute one as that is what we measure If bonds are broken, energy is absorbed from the surroundings, H is positive (endothermic) If bonds are created, energy is lost to the surroundings, H is negative (exothermic) So which way round is the enthalpy sign? Crystallisation of a drug from the liquid to the solid state (HC) (where C stands for crystallisation) Melting of a drug (HF) (where F stands for fusion = melting) Evaporation of a volatile solvent (HV) (where V stands for vaporization)  THE 2ND AND 3RD LAWS OF THERMODYNAMICS For many years it was believed that reactions were driven by enthalpy Thought that exothermic reactions would proceed spontaneously, endothermic required energy input However, many reactions take place spontaneously even though enthalpy change may not necessarily favour this taking place For example, diffusion of a gas into a vacuum  This key parameter is entropy (S) – related to disorder and probability 2nd law – the entropy of an isolated system will either increase or stay the same but may not decrease Informally – disorder tends to increase. If a reaction will result in greater disorder then it is more likely to happen Packs of cards, bedrooms, chimneys For example, protein unfolding falling down may be endothermic (bonds being The more disorder, the more entropy broken) but may occur without further heating due to entropy (S increases - positive)  Two (equivalent) ways of looking at this – probability and molecular motion Probability – if pack of cards dropped it can form an infinite number of random piles but only a very limited number of ordered ones (cf tidying bedroom) Therefore in the course of a reaction the more random/disordered event is more likely to occur  Molecular motions - entropy is also associated with molecular motions (rotational, vibrational) that do not perform work The greater the range of these possible motions (degrees of freedom), the greater the entropy Reactions that will result in a decrease in these motions (i.e. make them more ordered) do not tend to be favoured These motions are (almost) always present and increase with increased temperature They also decrease with decreased temperature Can we come to a point when they stop altogether? See a bit later……(3rd law)  THE CONCEPT OF HEAT CAPACITY A related concept to entropy – heat capacity This is the amount of heat to be supplied to an Material Specific object to produce a unit change in its temperature heat The SI unit of heat capacity is joule per kelvin (J/K) capacity at RT – for ‘specific’ divide by mass (J/kg. oK) This is hugely important in pharmaceutical Water 4181 engineering, but also reflects behaviour at a Copper 390 molecular level Wood 1200 Heat capacity reflects the ability to store heat Pyrex glass 780 energy Materials with higher range of molecular mobilities (degrees of freedom) can store more energy So materials with high heat capacity have higher  Returning to the idea of lower temperature leads to lower entropy – will this carry on forever? No – you have to get to a state where everything stops and is perfectly ordered The 3rd law of thermodynamics – at absolute zero the entropy of a perfectly crystalline substance is zero This is -273.15oC at which all molecular motion stops The Kelvin scale is always used for thermodynamics as it is a meaningful reference point that is not system dependent  SO WILL A REACTION TAKE Wrong question – pretty much any reaction can be PLACE OR NOT? MADE to occur if you put enough energy in Right question – will a reaction take place SPONTANEOUSLY? The answer will lie in the balance between the enthalpy and the entropy Free energy (G) is the arbiter between the two The Gibbs equation G = H - TS where G is the change in free energy  Free energy is the energy availably to perform work If it is negative, then the system can perform work on the surroundings and the reaction will be spontaneous If it is positive, then the system is not able to perform work on its surroundings and the reaction will not be spontaneous Free energy is like money – you have to spend it to do the stuff you want to do It is an incredibly important concept – you will meet it with equilibrium, drug binding, drug discovery, micellization and many other processes So a spontaneous reaction is favoured by a –ve H (heat given out to surroundings) and a +ve S (system becoming more disordered) But key issue is the balance between the two – spontaneous reactions could be endothermic if entropy sufficiently positive Systems will tend to go to state of lowest free energy (bit like a bank account being emptied UNLESS you earn money, but that isn’t spontaneous…,,,,)  THERMODYNAMICS IN THE BIOSCIENCES Thermodynamics is a vital component of pharmacy, pharmacology, biochemistry, chemistry, analytical chemistry, physics, engineering and many other topics Concept of being able to understand whether something will occur or not and with what energy change underpins understanding of all reactions For pharmacy and pharmacology, thermodynamics helps us to understand how drugs behave physically, chemically and biologically  THE DRUG DISCOVERY PROCESS Solubility, partitioning and melting point are amongst the first parameters measured for a new drug – all can be interpreted in terms of thermodynamic concepts Solubility – the maximum equilibrium concentration of a drug in a given solvent (indicative of behaviour in the body) Melting point – the transition from the crystalline to the liquid state (indicative of bond strength) Partitioning – the distribution of a drug between oil and aqueous phases (indicative of permeation across biological membranes) Drug receptor interactions Drugs act via specific interactions with receptors Understanding the nature of that binding and how it may be manipulated is at the heart of pharmacology Thermodynamics provides insights into bond strengths, free energy of interactions, molecular modelling and longevity of drug-receptor interactions  THANK YOU FOR YOUR ATTENTION See you in the workshops where we will reinforce your understanding of these ideas use these concepts to understand everyday events Use these concepts to understand pharmaceutical/pharmacological principles