William H. Hunter

Quantitative structure‐activity relationships: the Van't Hoff heats of transfer of resorcinol monoethers from water to n‐octanol

The partition coefficients of resorcinol and some resorcinol monoalkyl‐ethers from water to n‐octanol have been measured as a function of temperature. These data are used to evaluate ΔG, ΔH and ΔS for the solute transfer process. The data suggest direct calorimetric measurement of these parameters should be performed. Correlation with calori‐metrically determined ‘biological response’ will permit a more detailed and precise commentary upon the quantitative structure‐activity relationships for these compounds.

Enthalpies of solution of a series of m‐alkoxy phenols in water, n‐octanol and water‐n‐octanol mutually saturated: derivation of the thermodynamic parameters for solute transfer between these solvents

Enthalpies of solution in both water and n‐octanol have been determined for a series of phenols, in a microcalorimeter modified for titration. The thermodynamic data for solution in n‐octanol and in water, as well as for transfer between the two, have been calculated from the free energies of transfer, based upon partition coefficients, and the free energies of solution, based upon solubility data. The results are discussed in terms of solute‐solvent interactions in both phases and are used to assess, critically, the use of n‐octanol as lipid‐like solvent in QSAR studies.

Quantitative structure-activity relationships: microcalorimetric determination of a group additivity scheme for biological response

Abstract Flow microcalorimetric bioassay data for interaction of m -alkoxy phenols and for p -hydroxybenzoates have been obtained. Analysis of these data allows the identification of contributions toward the derived bioactivity from the parent structures (the molecule minus the n -CH 2 groups present in the side-chain) and the lipophilic groups, CH 2 . These results are discussed with respect to drug quantitative structure-activity relationships.

A thermodynamic analysis of the Collander equation and establishment of a reference solvent for use in drug partitioning studies

A thermodynamic analysis of the Collander equation, In PI = a + b In PII (I and II refer to two different partitioning systems with partition coefficients PI and PII, respectively), is given and applied to three forms of correlation. The intercept, a, is shown to have no general fundamental significance whereas the slope, b is shown to reflect differences in non‐aqueous solvent properties; b is also shown to be of use in scaling solvent behaviour to select solvents which closely represent biological membrane properties for use in partitioning studies. Laboratory and literature data are subjected to the analysis.

Microcalorimetric studies of the interaction of m-hydroxybenzoates with E. coli and with S. aureus. Demonstration of a Collander relationship for biological response

Abstract A linear relationship exists between the microcalorimetrically observed biological response to challenge of a sensitive organism by a series of drugs and the number of methylene groups present in the alkyl chains of these same drugs. A Collander type relationship is shown to exist for microcalorimetric response data obtained for interaction of alkyi m -hydroxybenzoates with Escherichia coli and Staphylococcus aureus .

Quantitative structure-activity relationships: a group additivity scheme for biological response of E. coli to the action of o-, m- and p-alkoxyphenol

Abstract Microcalorimetric assay of the antibacterial activity of 14 phenols shows that the activities can be expressed as two additive factors due to the aromatic portion and to the number of methylene groups.

Design and testing of a microtitration assembly for use with an LKB Batch Microcalorimeter

Abstract A twin, automatic microtitration assembly suitable for use with an LKB Batch Microcalorimeter is described. The apparatus, which can accurately and reproducibly deliver volumes as low as 1 μl, permits up to 20 titration additions to be made. It has been tested by the determination of the heat of ionisation of water at 303.15±0.01 K. The value determined compares favourably with the “best” value reported in the literature.

Thermodynamic parameters for transfer of resorcinol monoethers from water to heptane and to propylene carbonate. Derivation and analysis of group transfer thermodynamic parameters

Partition coefficients have been measured over a range of temperature for transfer of a series of resorcinol monoethers from water to heptane and to propylene carbonate (all solvents mutually saturated). These data have been used to evaluate ΔGtrs, ΔHtrs and ΔStrs. Further analysis allows assignment of ΔGtrs, ΔHtrs and ΔStrs values for transfer of a lipophilic group (CH2) and the ‘parent’ structure between the selected solvents. Transfer of a CH2 group is shown to be accompanied by a zero enthalpy change, whereas transfer of the parent structure results in ΔHtrs values dependent upon the non-aqueous solvent involved. These data are discussed in terms of partitioning and the use of a suitable bulk solvent to represent a biological lipid phase.

Microcalorimetric measurement of the enthalpies of transfer of a series of m-alkoxyphenols from isotonic aqueous solution to escherichia coli cells

Enthalpies of interactions of a series of m-alkoxyphenols with non-growing Escherichia coli suspended in a salt solution have been recorded. These data have been analysed on the assumption that the initial relatively rapid endothermic process represented the transfer of solute from aqueous solution to cells (ΔHtrs) and that the subsequent relatively lengthy exothermic process resulted from the biological consequences of the transfer process itself. The derived values are compared with values of ΔHtrs found for transfer of these solutes from water to octan-1-ol, heptane and propylene carbonate.

The preparation and pharmacological properties of ψ-corbasil

The synthesis is described of threo‐α‐methyl noradrenaline (ψ‐corbasil). The assignments of the erythro and threo configurations to corbasil and ψ‐corbasil respectively are supported by the evidence of the nmr spectra. Some preliminary results are reported for the relative pharmacological activity of the two isomers at α‐ and β‐adrenergic receptors.