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Effects of Buffers and pH on the Reaction of a trans ‐Platinum Complex with 5′‐Guanosine Monophosphate
Author(s) -
Li Chan,
Ding Yi,
Cheng Lanjun,
Zheng Yuchuan,
Sletten Einar,
Liu Yangzhong
Publication year - 2015
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201500728
Subject(s) - chemistry , deprotonation , adduct , guanosine , medicinal chemistry , aquation , inorganic chemistry , platinum , phosphate , stereochemistry , supramolecular chemistry , nuclear chemistry , catalysis , reaction rate constant , organic chemistry , molecule , kinetics , biochemistry , ion , physics , quantum mechanics
Abstract The aquation of platinum anticancer drugs is a crucial step for their activation and the consequent binding to the target DNA. These processes can be influenced by small molecules, such as carbonate and phosphate, which are present in high concentration in physiological conditions. In this work, the effects of buffer and pH on the reaction of trans‐EE { trans ‐[PtCl 2 { E ‐HN=C(OCH 3 )CH 3 } 2 ]} with 5′‐guanosine monophosphate (5′‐GMP) have been studied in detail. The reactions were monitored by HPLC at different pH in the presence of carbonate, phosphate, and HEPES [4‐(2‐hydroxyethyl)‐1‐piperazineethanesulfonic acid] buffers. trans‐EE showed a very low affinity for the nitrogen atoms of HEPES, but formed monofunctional adducts with carbonate and phosphate ions. The platination of GMP by trans‐EE was significantly affected by the choice of buffer and pH. Carbonate buffer decreased the reaction rate, mostly due to its competition with GMP. Although phosphate buffer formed a similar monofunctional adduct with trans‐EE , it had a negligible effect on the platination rate of GMP. This may be due to the formation of ternary adducts with trans‐EE and GMP. In all cases, the platination reaction was slower at higher pH, probably due to the deprotonation of an aqua ligand on the mono‐aqua complex of trans‐EE . The results in this paper indicate that the solution conditions have a different effect on the reaction of trans ‐platinum complexes compared with cisplatin.