From mutagenic to non-mutagenic nitroarenes: effect of bulky alkyl substituents on the mutagenic activity of nitroaromatics in Salmonella typhimurium. Part II. Substituents far away from the nitro group.
Derivatives of 4-nitrobiphenyl, 4-nitrosobiphenyl, 2-phenyl-5-nitropyridine (2-aza-4-nitrobiphenyl) and 2-nitrofluorene, bearing various alkyl substituents far away from the nitro group (4'-position in nitrobiphenyls, 7-position in 2-nitrofluorenes) were synthesised and tested for mutagenic potency in strains TA98 and TA100 of Salmonella typhimurium. In the absence of S9 in both strains, mutagenicity of all4'-Ad (Ad=adamantyl). Changes of the molecular shape from 'planar' to non-planar caused by the bulk of the introduced substituents (without influencing the twisting of the nitro substituent or the phenyl rings in the biphenyl compounds) may be responsible for this effect by interfering with an efficient intercalation into DNA.A comparison between experimental and theoretical values as calculated from recently developed equations (QSAR) confirmed our previous results (see the preceding paper) that mutagenicity of alkyl-substituted nitroaromatics cannot be predicted by hydrophobicity and LUMO-energies alone without including steric parameters.
Klein
M
M
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein Strasse, 35032, Marburg, Germany.
Erdinger
L
L
Boche
G
G
D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000633:toxicity; D011725:Pyridines / Q000138:chemical synthesis / Q000633:toxicity; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
D001713:Biphenyl Compounds; D009153:Mutagens; D009574:Nitro Compounds; D011725:Pyridines