Tadashi Endo

Intermolecular association and geometrical shape as two factors controlling chemical reactions

BIOLOGICAL phenomena are highly specific1–4 and much effort has been devoted to establishing the relationship between biological activity and molecular shape. We report here the sharp dependence of selectivity in the oxidation of a pair of thiols on their structures or on environment, the mode of each dependence of selectivity being controlled dominantly by their tendency towards intermolecular association.

Gas–liquid partition chromatographic evidence that alkyl–phenyl interactions are specific for the shape of the alkyl group

Gas chromatographic studies have shown that the weak interaction between an alkane sample and the phenyl group in a stationary liquid varies in strength with the geometrical shape of the alkyl group and is more attractive for a cyclic alkyl group than for the corresponding straight-chain alkyl group.

Control of the degree of molecular recognition by shape-specific weak interactions between nonpolar groups

In oxidation of a pair of associating thiols [(1) and (2)], each having a phenyl or a hexyl group (R = n-C6H13, i-C6H13, cyclo-C6H11), it has been shown that the order of the selectivity [a measure of the degree of the recognition between (1) and (2)] for R (i.e.,n-C6H13-C6H13 >cyclo-C6H11) depends upon the strength of the phenyl–R interactions.

Marked effect of the shape of solvent molecules on molecular recognition in the oxidation of associating thiols

Oxidation of a pair of associating thiols (1 and 2), each having a binding site [–C(O)NHC(O)NH–] and a recognition site (R1 or R2), is examined in binary solvent mixtures of a propanol with water and organic co-solvents. The selectivity (r)—a measure of the degree of recognition of (1) by (2)[or of (2) by (1)]—in the oxidation is represented by the logarithmic ratio of the yield of an unsymmetrical disulphide to twice that of a symmetrical one. It is found that (i) higher selectivity is achieved when the non-polar group of a propanol in a mixed solvent resembles a given non-polar group of one of the reacting molecules in three-dimensional shape and (ii) the above ‘solvent shape effect’ on the selectivity is produced more markedly in aqueous propanols than in the corresponding non-aqueous ones. Correlation of the observed selectivity with physico-chemical properties of (aqueous) propanols, reactivity difference between thiols, and so on is discussed together with a possible explanation of the solvent shape effect on the degree of recognition of non-polar groups.

Specific group–group interactions: determination of the enthalpies of specific group–phenyl interactions by gas–liquid partition chromatography

Gas chromatographic studies have shown that the enthalpy of the weak interaction of a polar or related group (e.g. vinyl, amino, carbonyl, or nitro group) in a sample molecule with the phenyl group in a stationary liquid alters markedly from –0.1 to –1.7 kcal mol–1 with the polar or related group.

Shape similarity effect on the strength of weak interactions of a phenyl group with unsaturated hydrocarbons and ethers

Gas chromatographic studies for pairs of six-membered-ring(cyclic) and straight-chain hydrocarbons and ethers have shown that the weak interactions of the phenyl group in a stationary liquid are more attractive with the cyclic hydrocarbons and ethers, which are similar in shape to the phenyl group, than with the straight-chain hydrocarbons and ethers, each pair containing the same number of π-electrons or oxygen atoms.

Shape similarity between solute and solvent molecules: its role in specific molecular recognition in hydrocarbon-containing solvents

Oxidation of a pair of associating thiols (1 and 2), each having a binding site [–C(O)NHC(O)NH–] and a recognition site (R1 or R2), is examined mainly in hydrocarbon-containing (aqueous) alcohols. The selectivity (r), a measure of the degree of recognition of 1 by 2(or of 2 by 1), in the oxidation is defined as the logarithmic ratio of the yield of an unsymmetrical disulfide to twice that of a symmetrical one. It is found that (i) higher selectivity is achieved when a hydrocarbon similar in shape to R2 is present in (aqueous) ethanol and (ii) the selectivity for R2= Ph (= R1) is higher in pure benzene than in aqueous ethanol. Correlation of the observed selectivity with physicochemical properties (relative permittivity and viscosity) of the pure solvents, reactivity difference between thiols, and other factors is discussed, together with a possible explanation of the specific recognition in terms of a ‘shape similarity effect’.

A novel parameter (S1) for three-dimensional shape similarity between groups: correlation with molecular recognition and biological activity

A new parameter (S1) representing the three-dimensional shape similarity between groups is defined as the degree of a maximal overlap between a pair of groups located within a three-dimensional grid. S1, which ranges from 0 to 1, has been calculated for 105 pairs of groups including straight-chain (C1–C6), branched (C4–C6), and cyclic alkyl groups, and a phenyl group. A close relationship has been found to exist between S1 and (i) the degree of the discrimination between groups by a given group in the oxidation of a pair of associating thiols and (ii) relative biological activity (i.e., effect on cat blood, pressure) of a homologous series of benzilic esters.

Marked effect of the three-dimensional shape of solvent molecules on chemical selectivity

In the oxidation of a pair of associating thiols [(1) and (2)] with oxygen in propan-1-ol–water and propan-2-ol–water mixtures, the selectivity is controlled by the three-dimensional shape of the propanols.

Correlation between selectivity in photochemical cross-cycloaddition and ionization potential of the reacting olefins

The selectivity (the ratio of crossadducts to homodimers) in the photochemical [2 + 2] cross-cyclo-addition of a 1 : 1 mixture of several series of (E)-olefins (1) and methyl p-nitro-(E)-cinnamate (2) was found to increase regularly with decreasing ionization potential of (1).