Substantivity of sunscreens—preparation and evaluation of some quaternary ammonium benzophenone derivatives

In continuation of previous studies on keratin-substantive sunscreens, two series of quaternary ammonium compounds, derived from 2,4-dihydroxy and from 4-hydroxybenzophenone and containing O-alkyl and N-alkyl chains of different length were prepared and submitted to substantivity tests on wool, to microbiological tests on two bacterial and two fungal species, and to tests for allergenicity/irritation on human skin. All compounds were rapidly adsorbed by wool in aqueous solution: as expected, the maximum amounts adsorbed at equilibrium (S_max), indicative of the skin substantivity, were greatest for the C12 N-alkyl derivatives, and showed a progressive decrease with increasing length of the N-alkyl substituent. No substantial substantivity differences were detected in four C12 quaternary derivatives, differing by the presence (or absence) of a 2-OH group in the benzophenone moiety and by the length of the O-alkyl ( n = 2 or 3) side chain. When tested for antimicrobial activity, however, only the 4-hydroxybenzophenone C12 quaternary derivatives showed an order of activity comparable with that of two reference compounds. The conditions leading to a maximal antibacterial activity in the present compounds appeared to be the absence of the 2-OH group, and a shorter O-alkyl side chain. None of the new quaternary derivatives showed skin-irritant properties. The results of this investigation, while confirming the peak substantivity of C12 quaternary derivatives, indicate the possibility of dissociating, in a quaternary ammonium sunscreen, the skin substantivity from other unwanted side-effects, and offer some guidelines for the development of safer agents of this type.