Solvation Effects, Reactivity Studies and Molecular Dynamics of Two Phosphonic Acids – Theoretical Investigation

Cancer metastasis or the spread of cancer cells from main tumor to other parts of the body is the most common cause of morbidity and mortality in cancer patients. Due to applications of risedronate (RES) and zoledronate (ZLA) in the medical field, the solvation effects, reactivity studies, and molecular dynamics (MD) are reported. The solvation-free energy in water (hydration-free energy) indicates good solubility in an aqueous medium, a factor that corroborates the biological activity. The O…H distances (P=O to OH) gives interactions in vacuum and solvents. Change in free energy for the RES and ZLA with both solvents indicated the process happen in spontaneously. Van der walls interactions demonstrated that the intramolecular hydrogen bonds at O4–C15 (RES) and at O8–H21, O3–H22, N10–H19, and O6–H17 (ZLA). MD and simulation of the ligand bound main WNT5A were studied in details to understand the nature of possible binding motifs and structurally stable conformations.

癌症转移（cancer metastasis），即癌细胞从原发肿瘤扩散至身体其他部位，是导致癌症患者发病与死亡的最常见诱因。鉴于利塞膦酸钠（risedronate, RES）与唑来膦酸（zoledronate, ZLA）在医学领域的应用，本研究报道了二者的溶剂化效应、反应性研究及分子动力学（molecular dynamics, MD）模拟结果。水中的溶剂化自由能（亦称水合自由能，hydration-free energy）表明二者在水相介质中具备良好溶解性，该特性可印证其生物学活性。O…H键距（P=O至OH）可反映真空与溶剂环境中的分子相互作用情况。利塞膦酸钠与唑来膦酸在两种溶剂中的自由能变化均显示，该过程可自发进行。范德华相互作用（Van der walls interactions）分析表明，利塞膦酸钠存在O4–C15位点的分子内氢键，唑来膦酸则存在O8–H21、O3–H22、N10–H19及O6–H17位点的分子内氢键。本研究还对配体结合型WNT5A开展了详细的分子动力学模拟分析，以探究其潜在结合基序的本质与结构稳定构象。