环磷酸腺苷钠结晶水的形成机制与调控

Crystal products of nucleotides can exist in the form of various hydrates. Crystal water has an effect on the crystal form and habit of product, and then it affects the physical and chemical properties of products, which is the main factor restricting the development of such products to high-end.To date, the formation mechanism of crystal water is still not clear, which results in the difficulty to rationally control the content of crystal water for given nucleotide compound. In this paper, taking adenosine 3′,5′- cyclic mono-phosphate sodium (cAMPNa) for example, on the basis of experiment, introducing the concept of "residual space", we investigate the crystallization process of cAMPNa solution from in various aspects by means of molecular simulation, to explore auto-assembly mechanism of water molecules participating in cAMP- and Na+ at micro level, and attempting to elucidate the formation mechanism of crystal water. Furthermore, we try to search a key factor that depending on crystal water, and establish the relationship between the environment conditions and the content of crystal water of final product, to control the crystal water of cAMPNa during its crystallization. The research achievements would be expected to provide a reference for other nucleotides.

核苷酸类物质的晶体产品可以以多种结晶水合物的形式存在，结晶水会影响产品的晶型和晶习，进而影响到产品的物化性质，是制约此类产品质量向高端化发展的重要因素。目前，其结晶过程中结晶水的形成机制尚不清晰，导致结晶水的个数难以科学调控。本项目拟以3′,5′-环磷酸腺苷钠（cAMPNa）为研究对象，以实验为基础，引入“剩余空间”的概念，借助分子模拟的手段从不同层面、不同角度研究cAMPNa溶液结晶过程，试图剖析水分子在微观层面参与cAMP-和Na+的自组装机制，探索cAMPNa在结晶过程中结晶水的形成机制，确立微观层面影响其结晶水个数的关键因素，借此建立起结晶表观因素和最终所形成的产品结晶水个数之间的相关性，以实现cAMPNa在结晶过程中结晶水的调控，为此类物质的结晶水问题的认识和解决提供参考。

针对核苷酸类物质结晶水的存在性和多样性问题，本项目以3′-5′-环磷酸腺苷钠盐（cAMPNa，化学计量型水合物）和 5′-尿苷酸（UMP，非化学计量型水合物）为例，提出了“剩余空间效应”，阐明了结晶水的形成机制，回答了为什么核苷酸类物质在结晶过程中容易形成结晶水合物，以及为什么可以形成含有不同个数结晶水的晶体。在此基础上，开发了晶型与粒度调控的共性技术与绿色转晶技术，在核苷酸、尼龙盐、虫草素等多种有机小分子上实现推广应用。