ANTIRADIATION COMPOUNDS .24. STABILITY OF COPPER(II) COMPLEXES OF BIS(METHYLTHIO) AND METHYLTHIO AMINO DERIVATIVES OF 1-METHYLPYRIDINIUM-2-DITHIOACETIC AND 1-METHYLQUINOLINIUM-2-DITHIOACETIC ACIDS IN THE PRESENCE OF AMINO-ACIDS, SIMPLE PEPTIDES, AND A PROTEIN
Wo. Foye et S. Chatterji, ANTIRADIATION COMPOUNDS .24. STABILITY OF COPPER(II) COMPLEXES OF BIS(METHYLTHIO) AND METHYLTHIO AMINO DERIVATIVES OF 1-METHYLPYRIDINIUM-2-DITHIOACETIC AND 1-METHYLQUINOLINIUM-2-DITHIOACETIC ACIDS IN THE PRESENCE OF AMINO-ACIDS, SIMPLE PEPTIDES, AND A PROTEIN, Journal of pharmaceutical sciences, 85(8), 1996, pp. 810-814
The radiation-protective bis(methylthio) and methylthio amino derivati
ves of 1-methylpyridinium- and 1-methylquinolinium-2-dithioacetic acid
s, a series of non-thiol sulfur-containing compounds, have been examin
ed for their ability to complex Cu(II) ion and remain stable in the pr
esence of alpha-amino acids, peptides, and a protein. Copper-binding s
tability constants were found that were considered sufficiently large
to be capable of existence under cellular conditions, with log K-s val
ues in the range of 13-15. Copper-binding constants for alpha-amino ac
ids are comparable to those far the radioprotective ligands, but overa
ll binding constants for simple peptides are usually 10(4)-10(6) lower
in magnitude. Essentially no change was found in the UV spectra of th
e Cu(II) complexes in the presence of alpha-amino acids and simple pep
tides, and the binding capacity to bovine serum albumin was quite low
for two Cu(II) complexes of the best protective ligands, with values o
f 10(-6)-10(-7) M. The possibility that these radioprotectors may act
in vivo as copper complexes, possibly as superoxide dismutase mimics,
is thus feasible. The magnitude of the copper binding stability consta
nts, the lack of copper exchange between the radioprotective ligands a
nd amino acids or peptides, and the very low tendency of the copper co
mplexes of the radioprotective ligands to bind to a protein indicate t
he potential of the complexes to contribute to the radioprotective abi
lity of the ligands.