Kinetics in Solution

During the years 1945-67, Ronnie Bell had a large and active research group in the PCL which included visitors from all parts of the world. Much of the work could be termed physical organic chemistry, i.e. the use of physicochemical methods such as studies of kinetics, equilibria and isotope effects to discover the detailed mechanism of organic reactions. (In North America, Bell was often regarded as an organic chemist!). Kinetic methods were also used to investigate solution equilibria in inorganic systems, for example the incomplete dissociation of salts. A particular theme was the effect of charged substituents such as –NH₃⁺ and –SO₃^- on rates and equilibria.

Many of the reactions studied were those catalysed by acids and/or bases, arising from the time that Bell had spent in Brönsted's laboratory in 1928-32. These lend themselves particularly to studies of the hydrogen isotope effect, and the theoretical prediction that the kinetic isotope effect should be greatest when the proton is half transferred in the transition state was confirmed experimentally. Some of the effects observed – up to k^H/k^D= 20 at 298 K – were too great to be accounted for by conventional theories, and it was concluded that the motion of the proton was markedly non-classical, i.e. that it involved tunnelling, and this was later confirmed by work on temperature coefficients. This was the first time that quantum mechanical tunnelling for atom transfers had been unequivocally established, a finding which was important for the subsequent development of theories of reaction kinetics. A measurement of the dissociation constants of HCO₂H and DCO₂H gave a pK difference of 0.035 ± 0.02, in complete agreement with 0.037 ± 0.02 as calculated from the vibration frequencies of the acids and their anions. Much work was done on the reversible addition of water to the carbonyl group, and a definitive review by W.P. Jencks (JACS, 1987) was recently dedicated to this early work of the Bell group.

Most of the kinetic work employed traditional experimental methods such as dilatometry, gas evolution, conductivity or spectrophotometry - even on occasion, titration, although this was regarded as a form of slave labour. However, other methods were also brought into play. J.C. Clunie (1951) developed a thermal method for following reactions with half times between a few seconds and a few minutes, which depended on the small temperature changes produced by the reaction. Tape recorders and a metronome were used to record the data for faster systems. The system was applied succesfully in a number of cases, but was soon superceded by stopped flow and relaxation methods developed elsewhere, as discussed at the Faraday Discussion on Fast Reactions in 1954 (where Eigen gave methods for the study of ionic reactions in aqueous solutions with half times as short as 10^-9 s). In 1963, Ronnie suggested that John Albery should look into the use of the rotating disc electrode for measuring the rate of dissociation of weak acids. This turned out to be a profitable move, as will be discussed later.

Much of the work on acid-base catalysis involved halogenation reactions and there was a need to follow rapid changes in low halogen concentrations. This was achieved by measuring redox potentials: since a ten-fold change in concentration displaces the potential by 29 mV, such changes can be followed over many powers of ten, and by taking suitable precautions, concentrations could be followed down to 10^-10 M. By controlling the concentration of the other reactant in a buffer system very high rate constants could be measured for the halogenation of reactive species such as enols, phenols, anilines and their ions: fortunately none of the values obtained exceeded the theoretical maximum of 10¹⁰ dm³mol^-1s^-1 for diffusion-controlled reactions in solution! The same techniques were applied to the addition of bromine to olefins, and the results afforded ample scope for the testing of theories of substituent effects.

In 1960 John Albery started his D.Phil with Ronnie Bell with the aim of using the rotating disc electrode to measure the kinetics of fast proton transfers. At that time the papers of Levich had not been translated into English. So a friend of John's, a Christ Church graduate student writing a thesis on Turgenev was cajoled into spending weeks in the alien surroundings of the PCL translating Levich's papers. Another crucial development was the bribing of Miss Binnie with a cream tea to persuade her to persuade Hinsh to spend £200 on a Servomex Motor Controller. Suffice it to say that the kinetics of proton transfer to several weak acids were eventually measured, but for this purpose Eigen's methods were superior and so the rotating disc heralded the development of electrochemistry described below. However the study of physical organic chemistry was very flourishing at this time and a joint PCL/Dyson Perrins discussion group held regular fortnightly meetings; its leaders were Ronnie Bell, Dick Norman, Jeremy Knowles and John Albery. With the departure of Ronnie in 1967, John Albery's group concentrated their attention on the use of solvent isotope effects. Following Gold and Kresge (a frequent visitor to the PCL) important advances in the theory of the use of the solvent isotope effect for the elucidation of mechanism were made by Brian Robinson, now Professor at East Anglia. A successful distinction was made between the A1 and A2 mechanisms. At the time it seemed important, but nowadays the quantitative measurement of the degree of involvement in the transition state of an attacking nucleophilic water molecule is less glamorous.

More significant was the continuing collaboration between John Albery and Jeremy Knowles, which continues to the present day. Jeremy had wisely abandoned physical organic chemistry for the study of enzyme kinetics. His group carried out a heroic series of 18 different isotopic experiments using hydrogen, deuterium and tritium on the reaction of triose phosphate isomerase. John Albery provided the theoretical analysis of the experiments which allowed the complete free energy profile of the enzymatic reaction to be elucidated. A curious pattern emerged in which the transition states were all of comparable free energy as were the enzyme bound intermediates. Albery developed an efficiency function to explain why enzymes should have evolved to this particular pattern. At that time there was only triose phosphate isomerase. Fifteen years later results from the fifteen enzymes for which we now have free energy profiles show that they all obey the principles for the evolution of catalytic efficiency proposed by Albery and Knowles.

A regular academic visitor to the Bell and Albery groups was Professor Maurice Kreevoy. On one of these visits in 1977 Albery and Kreevoy analysed the extensive results for SN₂ reactions and showed that the Marcus theory could explain the patterns of reactivity, the relation between kinetics and thermodynamics and the behaviour in different types of solvent. This extension of the Marcus theory from electron and proton transfers to methyl reactions unified the classical preoccupations of physical organic chemistry. Another visitor was Rory More O'Ferrall, an ICI Fellow, and Albery More O'Ferrall diagrams were invented and applied to proton transfers and elimination reactions respectively.

Fred Dainton extended his established research in the area of radiation chemistry during the three years he was in Oxford although most of his experimental work was continued at the Cookridge Research Centre at Leeds. In addition, he established flash photolysis and laser flash photolysis systems at Oxford to study a range of electron and energy transfer problems in condensed phases. His radiation chemical interests were later continued by Mike Pilling and Nick Green who worked on the development of stochastic models of reaction and diffusion in the small clusters of reactive species which are generated by the passage of high energy radiation through a liquid. Green, now a Lecturer at King's College, London, has continued to work on a range of fundamental theoretical problems involving diffusion-controlled reactions.

A new line of research was started in 1976 with the development by Jon Hadgraft of the rotating diffusion cell for the study of reactions at liquid/liquid interfaces. The technique was applied to the study of the kinetics of drug delivery. Albery, Hadgraft and Guy were the first to show that drugs pass through the skin barrier by diffusing round rather than through the dead cells in the epidermis. Hadgraft and Guy went on to become Professors in Pharmacology Departments.

Reaction Kinetics: Gas Phase Chemical Kinetics and Bacterial Growth