The Role of Solvent in Tautomer Solvate Crystallization: A Case of 6-Amino-1,3-Dimethyl-5-Nitrosouracil  

作　　者：Luguang Qi Yanhui Jin Huina Li Yanpeng Dong Chuang Xie 

机构地区：[1]School of Chemical Engineering and Technology,Tianjin University,Tianjin 300072,China [2]Xinhua Pharmaceutical(Shouguang)Co.,Ltd,Weifang 262700,China [3]National Collaborative Innovation Centre of Chemical Science and Engineering(Tianjin),Tianjin 300072,China

出　　处：《Transactions of Tianjin University》2020年第6期458-469,共12页天津大学学报（英文版）

基　　金：The authors thank the fi nancial support from the National Natural Science Foundation of China(No.21776204).

摘　　要：Tautomers are structural isomers that readily interconvert and may exhibit diff erent properties.The eff ect of solvent on tautomeric equilibria in solution has been a subject of some research.Tautomer solvate is less common,and the role of solvent in the crystallization of tautomer solvate remains an interesting topic.In this work,we used 6-amino-1,3-dimethyl-5-nitrosouracil(NAU)as the tautomeric model material,which can present in nitrone–enamine form(Tautomer A)or oxime–imine form(Tautomer B).A solvate with NAU/DMSO ratio of 1:1 was discovered and characterized using single/powder X-ray diff raction and thermogravimetry.The crystal structure of NAU·DMSO was determined for the fi rst time,where only Tautomer A was formed in the tautomeric crystal.Quantum chemical calculation and molecular dynamics simulation were conducted to determine the tautomeric form in DMSO solution.Electrostatic potential analysis,radial distribution function analysis,and binding energy suggested possible DMSO–NAU interaction modes and stable tautomer complexes in solution.Tautomer A-containing complexes were found to dominate in solution,as verifi ed by comparing predicted and experimental 1 H NMR spectra.Findings reveal that the hydrogen bonding between DMSO and NAU is similar in solution and in NAU–DMSO solvate crystal,which helps preserve the form of Tautomer A during solvate crystallization.

关 键 词：TAUTOMERIZATION SOLVATE Molecular dynamics simulation Quantum chemical calculation 

分 类 号：O641.6[理学—物理化学]