Strategy to Regulate the Stability and Reduction Rate of Oxaliplatin-Based Pt(IV) Complexes: Cocrystallization

• Published in: Crystal growth & design Vol. 23; no. 9; pp. 6506 - 6516
• Main Authors: Zhu, Bin, Guo, Mei, Yao, Yi-Chen, Yao, Yu-Qian, Hong, Minghuang, Qi, Ming-Hui, Ren, Guo-Bin
• Format: Journal Article
• Language: English
• Published: American Chemical Society 06.09.2023
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/acs.cgd.3c00480

To overcome the clinical limitations of oxaliplatin (OXA), such as side effects and toxicity, increasing attention was paid to the use of OXA-based Pt­(IV) complexes as oral administration prodrugs. In this study, we prepared trans-[Pt­(R,R-DACH)­(oxalate)­(OH)2] (DHOXA) as a model of OXA-based Pt­(IV) complexes and synthesized six cocrystals of DHOXA to investigate their stability in pH 1.2 and 7.4 buffer and the reduction rate of producing OXA. Six cocrystals of DHOXA with oxalic acid, hydroquinone (HYD), benzoic acid, salicylic acid, 3,5-difluorobenzoic acid, and 3-hydroxy-2-naphthoic acid were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, and thermal analysis. Further contrastive analysis of the dissolution behavior and reduction test of the six cocrystals of DHOXA showed that DHOXA-HYD dihydrate (DHOXA-HYD-DH) significantly improved the performances of the stability in hydrochloric acid (pH 1.2) and the reduction rate. Besides, the cytotoxicity studies showed that DHOXA-HYD-DH increased cytotoxicity to cancer cells and possessed higher safety. The study provides a new method to develop the OXA-based Pt­(IV) complexes as prodrugs.