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Comparative antimicrobial activity studies for certain new classes of soft N-chloramines derived from α-aminoisobutyric acid and 2-amino-2-methyl-1-propanol were examined using the minimum inhibitory concentration (MIC) and/or the contact germicidal efficiency (CGE) procedures. Several factors significantly influence the antimicrobial activity of the soft N-chloramines: (a) the aliphatic chain length in a homologous series, (b) the degree of chlorination of the nitrogen atom, (c) the solution pH, (d) the presence of a denaturant, and (e) the nature of a positive charge.

1-Methylpyridine-2-carbaldehyde oxime, a quaternary pyridinium salt, can be delivered efficiently through the blood-brain barrier in its dihydropyridine prodrug form. This redox system was used to study the elimination rate from the brain of a small quaternary salt. It was found that the oxime is eliminated relatively fast from the brain, which supports a hypothesis for the existence of an active transport mechanism for eliminating organic ions from the brain. The possibilities of using the pyridinium salt in equilibrium dihydropyridine redox system for specific delivery of drugs to the brain are discussed.

Comparative antimicrobial activity of 3-chloro-2-oxazolidinone (I), 3-chloro-4-methyl-2-oxazolidinone (II), 3-chloro-4,4-dimethyl-2-oxazolidinone (III), and N-chlorosuccinimide (IV) was evaluated in aqueous buffers in the absence and presence of 5% horse serum. All four compounds had similar bactericidal activity in the absence of horse serum, but I and III had superior activity relative to IV when serum was present. Compound III was considerably more stable with respect ot loss of positive chlorine and bactericidal activity than I and II when stored in 0.1 M sodium dihydrogen phosphate buffered to pH 7.0 at 40 degrees. Thus, III is potentially the most useful bactericidal agent of those evaluated. The chlorine potentials of I, II, and III, the rate constants for transfer of positive chlorine from I and III to morpholine in aqueous solutions, and the hydrolytic stabilities of I and III with respect to loss of positive chlorine were evaluated. These data, together with previously calculated data for IV, are used to rationalize the observed bactericidal activities.

An N,N-dialkylhydroxylamine derivative of indomethacin has been synthesized. It has been shown to improve the delivery of indomethacin through mouse skin (compared to indomethacin itself) by a factor of two, to be more effective than indomethacin in inhibiting thermal inflammation (two to three times) in animal models, but to be only as effective as indomethacin in inhibiting UV-B radiation erythema in human volunteers.