1H NMR as an analytical tool for the investigation of hydrolysis rates: a method for the rapid evaluation of the shelf-life of aqueous solutions of drugs with ester groups.

The rate of hydrolysis of esters of primary and secondary alcohols can be determined quickly and easily by 1H NMR in aqueous solution, provided that the water signal is suppressed by the WATR (Water Attenuation by T2 Relaxation) method. To evaluate this approach, Arrhenius plots have been constructed for hydrolysis of acetylcholine, carbachol and atropine, and the effect of pH on the hydrolysis of procaine has been determined over a limited range. The results agree well with literature values for rate constants.

Antimicrobial activity and physico-chemical properties of some alkyldimethylbenzylammonium chlorides.

A series of alkyldimethylbenzylammonium chlorides have been synthesized with n-alkyl chain lengths of C1 leads to C18. Octanol/water partition coefficients were determined and the antimicrobial activity assessed as the minimum growth inhibitory concentrations towards twelve strains of micro-organisms, representative of Gram-negative and Gram-positive bacteria, yeasts and fungi. The data were subjected to a numerical analysis. Antimicrobial activity of the compounds was found to be a parabolic function of their lipophilicity and maximized with n-alkyl chain lengths of between C12 and C16. The data fit to quadratic functions estimated for low (C1-C7) and high (C8-C16) alkyl chain length compounds was better than for a single quadratic describing the activity of the complete series (C1-C18). These maximized at log P values corresponding to alkyl-chain lengths of approximately C7 and C14 respectively, and were suggestive of low and high affinity binding sites upon the cell surface. The data analysis allowed the chain lengths of compounds with optimal activity towards the various groups of organisms to be determined. Generally yeasts and fungi were most sensitive towards C12, Gram-positive bacteria towards C14, and the Gram-negative bacteria towards C16. Gram-negative cells were the most resistant towards all the compounds and Gram-positive cells the least.

Rate constants for drug release from micellar solutions of non-ionic surfactants.

The release of weak acid from micellar solutions containing different concentrations of two structurally related non-ionic surfactants was estimated using a dynamic dialysis apparatus. In all cases the effect of the surfactant was to reduce the amount of weak acid transferred. The data have been subjected to compartmental analysis using non-linear regression analysis. Rate constants for exchange cross the dialysis membrane were independent of surfactant concentration. As surfactant concentration increased the rate constants for transfer from the non-micellar region did not show a marked change.

Interrelation of DNA replication, specific growth rate and growth temperature in the sensitivity of Escherichia coli to cold shock.

Escherichia coli W3110 was grown in a chemostat under conditions of carbon limitation at various temperatures and specific growth rates (mu). Exponential survivor-time curves following cold osmotic shock were biphasic. These could be described by the sum of two exponential functions representing the survival of sensitive and resistant fractions of the population where the size of the sensitive fraction was directly proportional to mu. Decimal reduction times for the more resistant fraction were unaffected by mu yet decreased with increasing growth temperature. Sensitivity to cold shock was evaluated for an E. coli CR34 mutant, temperature-sensitive in initiation of DNA replication. When grown in the chemostat at the non-restrictive temperature (30 degrees C) sensitivity was directly proportional to mu. Following a rise in the incubation temperature to 42 degrees C, sensitivity decreased markedly and reached a minimum 45 to 60 min after the temperature increase. Sensitivity of the E. coli mutant grown at 30 degrees C and raised to 42 degrees C for 1 h was low and relatively unaffected by growth rate.

Effect of racemic and S(+) alpha-chlorohydrin-1-phosphate on glyceraldehyde-3-phosphate dehydrogenase in relation to its contraceptive action.

The phosphate esters of racemic (+/-) alpha-chlorohydrin and its S(+)-optical isomer have been prepared as cyclohexylamine salts. In vitro both inhibited glyceraldehyde-3-phosphate dehydrogenase by a competitive mechanism, whereas (+/-) alpha-chlorohydrin did not. The S(+)-isomer was approximately four times as potent as the racemate. These results correlate with data concerning the relative contraceptive activity in rats of racemic and S(+) alpha-chlorohydrin. They support the view that the antifertility mechanism involves in vivo formation of S(+) alpha-chlorohydrin-1-phosphate, with resulting inhibition of glycolysis in sperm.