Synthesis, Stability, and Antimicrobial Activity of Diiodobromides of 1H,2H,3H,4H-Pyrido-[4,3-d]Pyrimidinium Derivatives

Abstract

Iodination of chloroform solutions of the bromides of 1H,2H,3H, 4H-pyrido[4,3-d]pyrimidinium with a threefold excess of iodine was performed to synthesize the diiodobromides of the corresponding organic cations. The composition and structure of these compounds were confirmed by UV and 1 H NMR spectroscopic and potentiometric titration methods. Values for the stability constant lgb (3.05 -4.68) allowed active iodine concentrations at the bactericidal level to be produced in solutions of 1H,2H,3H, 4H-pyrido[4,3-d]pyrimidinium diiodobromides. The minimum inhibitory concentrations (MIC) of 1H,2H,3H,4H-pyrido[4,3-d]pyrimidinium diiodobromides against E. coli were 1.0 ± 0.25 mg/ml. Keywords: bromides and diiodobromides of 1H,2H,3H,4H-pyrido[4,3-d]pyrimidinium derivatives, stability of iodohalogenides, antimicrobial activity.Polyhalogenides of nitrogen-containing organic cations have recently been the subject of interest as iodine in the bound state has virtually no toxicity but retains its biological activity [1]. The creation of new drugs able to release molecular iodine gradually and maintain its concentration at the bactericidal level therefore has potential [2].We have previously established the structure and coordinating capacity of 1,3-dimethyl-2,4-dioxo-R-1H,2H,3H,4H-pyrido[4,3-d]pyrimidinium (where R = phenyl or p-bromophenyl) in relation to molecular iodine [3].The studies reported here addressed the bromides and diiodobromides of organic cations based on 1H,2H,3H,4H-pyrido[4,3-d]pyrimidinium.The aim of the present work was to prepare complexes of the bromides of 1H,2H,3H,4H-pyrido[4,3-d]pyrimidinium derivatives with molecular iodine and study their stabilities and antimicrobial activities. = R 3 = H -1,3-dimethyl-2,4-dioxo-5,6,7-triphenyl-1H,2H,3H,4H-pyrido[4,3-d]pyrimidinium bromide (I) and diiodobromide (I¢); R 1 = R 2 = H, R 3 = Br -5,6-diphenyl,7-(p-bromophenyl)-1,3-dimethyl-2,4-dioxo-1H,2H,3H,4H-pyrido[4,3-d]pyrimidinium bromide (II) and diiodide (II¢); R 1 = H, R 2 = R 3 = Br -5-phenyl-6,7-bis(p-bromophenyl)-1,3-dimethyl-2,4-dioxo-1H,2H,3H, 4H-pyrido[4,3-d]pyrimidinium bromide (III) and diiodide (III¢); R 1 = R 2 = R 3 = Br -5,6,7-tri(p-bromophenyl)-1,3-dimethyl-2,4-dioxo-1H,2H,3H,4H-pyrido[4,3-d]pyrimidinium bromide (IV) and diiodide (IV¢); R 1 = H, R 2 = R 3 = OCH 3 -6,7-bis(4-methoxyphenyl)-1,3-dimethyl-2,4-dioxo-5-phenyl-1H,2H,3H,4H-pyrido[4,3-d]pyrimidinium bromide (V) and diiodide (V¢); R 1 = H, R 2 = R 3 = NO 2 -6,7-bis(4-nitrophenyl)-1,3-dimethyl-2,4-dioxo-5-phenyl-1H,2H,3H,4H-pyrido[4,3-d]pyrimidinium bromide (VI) and diiodide (VI¢).