Antiradiation compounds. 24. Stability of copper (II) complexes of bis(methylthio) and methylthio amino derivatives of 1-methylpyridinium- and 1-methylquinolinium-2-dithioacetic acids in the presence of amino acids, simple peptides, and a protein.
The radiation-protective bis(methylthio) and methylthio amino derivatives of 1-methylpyridinium- and 1-methylquinolinium-2-dithioacetic acids, a series of non-thiol sulfur-containing compounds, have been examined for their ability to complex Cu(II) ion and remain stable in the presence of alpha-amino acids, peptides, and a protein. Copper-binding stability constants were found that were considered sufficiently large to be capable of existence under cellular conditions, with log K beta values in the range of 13-15. Copper-binding constants for alpha-amino acids are comparable to those for the radioprotective ligands, but overall binding constants for simple peptides are usually 10(4)-10(6) lower in magnitude. Essentially no change was found in the UV spectra of the Cu(II) complexes in the presence of alpha-amino acids and simple peptides, and the binding capacity to bovine serum albumin was quite low for two Cu(II) complexes of the best protective ligands, with values of 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 constants, the lack of copper exchange between the radioprotective ligands and amino acids or peptides, and the very low tendency of the copper complexes of the radioprotective ligands to bind to a protein indicate the potential of the complexes to contribute to the radioprotective ability of the ligands.
Foye
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Department of Chemistry, Massachusetts College of Pharmacy and Allied Health Sciences, Boston, MA 02115, USA.
Chatterji
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D000596:Amino Acids / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D004355:Drug Stability; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011726:Pyridinium Compounds / Q000737:chemistry*; D011806:Quinolinium Compounds / Q000737:chemistry*; D011837:Radiation-Protective Agents / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
D000596:Amino Acids; D010455:Peptides; D011726:Pyridinium Compounds; D011806:Quinolinium Compounds; D011837:Radiation-Protective Agents; D012710:Serum Albumin, Bovine; D003300:Copper