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.

中文翻译：

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调节奥沙利铂基 Pt(IV) 配合物稳定性和还原率的策略：共结晶

为了克服奥沙利铂 (OXA) 的临床局限性，如副作用和毒性，基于 OXA 的 Pt(IV) 配合物作为口服前药的使用越来越受到关注。在本研究中，我们制备了反式-[Pt(R,R-DACH)(草酸盐)(OH) ₂] (DHOXA) 作为 OXA 基 Pt(IV) 配合物的模型，合成了 DHOXA 的六种共晶，以研究它们在 pH 1.2 和 7.4 缓冲液中的稳定性以及产生 OXA 的减少率。通过单晶 X 射线衍射、粉末 X 射线对 DHOXA 与草酸、氢醌 (HYD)、苯甲酸、水杨酸、3,5-二氟苯甲酸和 3-羟基-2-萘酸的六种共晶进行了表征衍射和热分析。进一步对比分析DHOXA的六种共晶的溶解行为和还原实验表明，DHOXA-HYD二水合物（DHOXA-HYD-DH）显着提高了在盐酸（pH 1.2）中的稳定性和还原率性能。此外，细胞毒性研究表明DHOXA-HYD-DH增加了对癌细胞的细胞毒性，具有更高的安全性。