Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
J Am Chem Soc. 2012 Feb 22;134(7):3590-7. doi: 10.1021/ja211530n. Epub 2012 Feb 10.
Trimethylamine-N-oxide (TMAO) and urea represent the extremes among the naturally occurring organic osmolytes in terms of their ability to stabilize/destabilize proteins. Their mixtures are found in nature and have generated interest in terms of both their physiological role and their potential use as additives in various applications (crystallography, drug formulation, etc.). Here we report experimental density and activity coefficient data for aqueous mixtures of TMAO with urea. From these data we derive the thermodynamics and solvation properties of the osmolytes, using Kirkwood-Buff theory. Strong hydrogen-bonding at the TMAO oxygen, combined with volume exclusion, accounts for the thermodynamics and solvation of TMAO in aqueous urea. As a result, TMAO behaves in a manner that is surprisingly similar to that of hard-spheres. There are two mandatory solvation sites. In plain water, these sites are occupied with water molecules, which are seamlessly replaced by urea, in proportion to its volume fraction. We discuss how this result gives an explanation both for the exceptionally strong exclusion of TMAO from peptide groups and for the experimentally observed synergy between urea and TMAO.
三甲胺 N-氧化物（TMAO）和尿素在其稳定/不稳定蛋白质的能力方面代表了天然存在的有机渗透物的极端情况。它们的混合物存在于自然界中，其生理作用及其作为各种应用（晶体学，药物配方等）添加剂的潜在用途都引起了人们的兴趣。在这里，我们报告了 TMAO 与尿素的水混合物的实验密度和活度系数数据。根据这些数据，我们使用 Kirkwood-Buff 理论得出了渗透物的热力学和溶剂化性质。TMAO 氧上的氢键作用强烈，加上体积排阻，解释了 TMAO 在尿素水溶液中的热力学和溶剂化作用。结果，TMAO 的行为方式与硬球非常相似。有两个必需的溶剂化位点。在普通水中，这些位置被水分子占据，而尿素则根据其体积分数按比例取代水分子。我们讨论了这一结果如何解释 TMAO 从肽基团中异常强烈的排除以及实验观察到的尿素和 TMAO 之间的协同作用。
