This aimed to develop a comprehensive theoretical protocol for examining substitution reaction processes. The researchers used a theoretical quantum-mechanical protocol based on the QM-ORSA approach, which estimates the kinetic parameters of thermodynamically favourable reaction pathways. This theoretical protocol was validated by experimentally investigating substitution mechanisms in two previously synthesised Pd(II) complexes: chlorido-[(3-(1-(2-hydroxypropylamino)ethylidene)chroman-2,4-dione)]palladium(II) (C1) and chlorido-[(3-(1-(2-mercaptoethylamino)-ethylidene)-chroman-2,4dione)]palladium(II) (C2), along with biologically relevant nucleophiles, namely L-cysteine (L-Cys), L-methionine (L-Met), and guanosine-5′-monophosphate (5′-GMP). Reactions were investigated under pseudo-first-order conditions, monitoring nucleophile concentration and temperature changes using stopped-flow UV-vis spectrophotometry. All reactions were conducted under physiological conditions (pH = 7.2) at 37 °C. The reactivity of the studied nucleophiles follows the order: L-Cys > L-Met > 5′-GMP, and the reaction mechanism is associative based on the activation parameters. The experimental and theoretical data showed that C2 is more reactive than C1, confirming that the complexes’ structural and electronic properties greatly affect their reactivity with selected nucleophiles. The study's findings have confirmed that the primary interaction occurs with the acid–base species L-Cys, mostly through the involvement of the partially negative sulfur atom (87.2%). On the other hand, C2 has a higher propensity for reacting with L-Cys⁻, primarily through the partially negative oxygen atom (92.6%). The implementation of this theoretical framework will significantly restrict the utilization of chemical substances, hence facilitating cost reduction and environmental protection.

中文翻译：

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酸碱平衡对某些单功能香豆素 Pd(II) 配合物与生物相关亲核试剂相互作用的影响 - 综合动力学研究

其目的是开发一个用于检查取代反应过程的综合理论方案。研究人员使用基于 QM-ORSA 方法的理论量子力学协议，该协议估计热力学上有利的反应途径的动力学参数。该理论方案通过实验研究两种先前合成的 Pd( II ) 配合物中的取代机制得到了验证：氯化物-[(3-(1-(2-羟基丙氨基)亚乙基)苯并二氢吡喃-2,4-二酮)]钯( II ) ( C1 ) 和氯代-[(3-(1-(2-巯基乙基氨基)-亚乙基)-苯并二氢吡喃-2,4二酮)]钯( II ) ( C2 )，以及生物学相关的亲核试剂，即L -半胱氨酸 ( L -Cys）、L-蛋氨酸（L -Met）和鸟苷-5'-单磷酸（5'-GMP）。在伪一级条件下研究反应，使用停流紫外可见分光光度法监测亲核试剂浓度和温度变化。所有反应均在 37°C 的生理条件（pH = 7.2）下进行。所研究的亲核试剂的反应性遵循以下顺序：L -Cys > L -Met > 5′-GMP，并且反应机制是基于激活参数的关联。实验和理论数据表明，C2比C1更具反应性，证实配合物的结构和电子性质极大地影响其与所选亲核试剂的反应性。研究结果证实，主要相互作用发生在酸碱物质L -Cys 上，主要是通过部分带负电的硫原子 (87.2%) 的参与。另一方面，C2更倾向于与L -Cys ^-发生反应，主要是通过部分带负电的氧原子 (92.6%)。这一理论框架的实施将极大地限制化学物质的使用，从而有利于降低成本和保护环境。