Experimental and theoretical studies on the complexes between cisplatin and guanidinoacetic acid

详细信息    查看全文

• 作者：Jussara L. Miranda^a ; ^{jussara@iq.ufrj.br" class="auth_mail" title="E-mail the corresponding author} ; Luiza C. Moura^a ; Rosane A.S. San Gil^a ; Maurí ; cio T.M. Cruz^b ; Anderson C.O. Silva^a ; Á ; urea A. Barbosa^a
• 关键词：Cisplatin ; Guanidinoacetic acid ; 195Pt NMR ; Potentiomety ; Stability constants
• 刊名：Polyhedron
• 出版年：2015
• 出版时间：14 December 2015
• 年：2015
• 卷：102
• 期：Complete
• 页码：313-320
• 全文大小：1301 K

文摘

Cisplatin, cis-dichlorodiammineplatinum(II) is one the most employed antineoplasic drugs, exhibiting activity for different types of tumors. Cisplatin resistance can be related to its reduced uptake or retention, causing the decrease of the platinum–DNA adduct. This is attributed to cisplatin binding to other cellular components, causing its deactivation or damage to its normal biochemical pathway. Several studies with a focus on elucidating cisplatin binding to compounds present in cells have been conducted. In the present study, the interaction of cisplatin with one potential O and N-donor ligand, guanidinoacetic acid, was investigated, an amino acid found at high concentrations in the kidney and liver, organs where the drug accumulates. In vitro GAA and cisplatin interaction was studied in aqueous medium at the same ionic strength (0.1 mol L⁻¹ KCl) and temperature (36.5 °C) as fluids of the body. Potentiometric and NMR (¹H and ¹⁹⁵Pt) analyses have been done, with the determination of stability constants and theoretical calculations for the principal structures involved. Results showed that GAA may be one of the potential biomolecules of cisplatin since, under the conditions of temperature and ionic strength of the body at around pH 7, part of cisplatin interacted with GAA to form [Pt(NH₃)₂(HGAA)₂]²⁺. Optimization of this species, [Pt(NH₃)₂(HGAA)₂]²⁺ was carried out using the gaussian 03 package with the B3LYP function in combination with LANL2DZ (6–311G(d,p)), yielding a planar sphere coordination around Pt(II) and also O–H intramolecular interactions in the complex. The results on speciation for cisplatin/GAA systems could be of great interest since GAA may be one of the potential binding species of cisplatin, especially in the study of 5:1 cisplatin/GAA ratio (found in rats, for example).