A series of anti, anti-dichloro-N-substituted azaadamantanes have been synthesized (Henkel et al, 1981, J. Org. Chem. , 46, 3483) representing conformationally rigid nitrogen mustards incorporated into an adamantyl framework with well defined stereochemistry and fixed separation distances between alkylating centers of 3.6 A (1) and 2.5 X (2,3) (Henkel et al, 1981, J. Org. Chem., 46, 3483) to be used as structurally rigid probes of DNA alkylation and intermolecular crosslink formation leading to cytotoxicity. The aqueous solution stability and the extent of intermolecular DNA crosslink formation for both the N-methyl and N-piperdinoethyl series of isomers have been measured using novel modifications of an ethidium bromide fluorescence assay technique. Results indicate that isomers 1 and 2 of both series form intermolecular crosslinks to an appreciable extent, while little or no crosslinking is observed under similar conditions for isomer 3 of both series. Analysis of the aqueous solution stability, time dependent crosslinking reaction isotherms and crosslink stability indicate significant differences both within and between series, which suggests stereospecific crosslinking behavior at the molecular level.
Library of Congress Subject Headings
Recombinant DNA--Analysis; DNA--Analysis; Nitrogen mustards; Genetic toxicology
Department, Program, or Center
School of Chemistry and Materials Science (COS)
Robbins, Harry, "A comparative analysis of DNA molecular crosslinking by dichloro-N-substituted azaadamantane isomers" (1985). Thesis. Rochester Institute of Technology. Accessed from
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