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SOME CHEMICAL PROPERTIES UNDERLYING ARSENIC'S BIOLOGICAL ACTIVITY
Citation:
Kitchin, K T., K. A. Wallace, AND P. Andrewes. SOME CHEMICAL PROPERTIES UNDERLYING ARSENIC'S BIOLOGICAL ACTIVITY. SEGH Conference on Arsenic, San Diego, CA, July 14-18, 2002.
Description:
ABSTRACT
In this paper some of the chemical properties of arsenicals (atomic
and molecular orbitals, electronegativity, valence state, changes between
valence state, nucleophilicity, the hard/soft acid/base principle) that may
account for some of the biological activity of arsenicals are presented.
Trivalent arsenicals can act as soft acids while pentavalent arsenicals tend
to act as borderline soft to hard acids. As soft acids, trivalent arsenicals
have a high propensity to bond with soft bases, which in biological systems
are usually sulfur (e. g. cysteine moieties of proteins) and selenium
containing compounds. This soft acid property of trivalent arsenicals can
lead to many of the proposed modes of carcinogenesis (e. g. altered DNA
repair, altered growth factors, cell proliferation, altered DNA methylation
patterns and promotion of carcinogenesis). Trivalent arsenicals can act as
nucleophiles, whereas pentavalent arsenicals normally do not. Because of
much less electrostatic repulsion, nonionized trivalent arsenicals are more
capable of interacting with negatively charged DNA than negatively charged
pentavalent arsenicals. Experimental binding studies with 73As arsenite to a
model peptide of 25 amino acids and 4 free sulfhydryl groups (based on a
zinc finger region of the human estrogen receptor alpha) gave a Kd
(dissociation equilibrium constant) of 8.1 uM and a Bmax (concentration of
binding sites for the Iigand) of 107 nmol/mg protein. This arsenite binding
was dependent on (a) the presence of free sulfhydryls in the peptide and (b)
trivalency of the arsenical (i. e. arsenite binds well, arsenate does not).
This abstract does not necessarily reflect the US EPA Policy.