Department of Chemistry and Biochemistry, Center for Discovery and Innovation, The City College of New York, New York, NY, 10031, USA; Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY, 10016, USA.
Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, 08854, USA.
Carbohydr Res. 2022 Nov;521:108647. doi: 10.1016/j.carres.2022.108647. Epub 2022 Aug 18.
Sucralose differs from sucrose only by virtue of having three Cl groups instead of OH groups. Its intriguing features include being noncaloric, noncariogenic, ∼600 times sweeter than sucrose, stable at high temperatures/acidic pH's, and void of disagreeable aftertastes. These properties are attractive as food additive, one of which is as hydrogel obtainable via the technique of molecular gelation using a sucralose-derived low-molecular weight gelator (LMWG). Such hydrogels are highly responsive to external stimuli like temperature, because the LMWGs self-assemble via non-covalent interactions and could thus be utilized in applications like control-release. We found that sucralose to be unreactive under lipase biocatalysis, unlike sucrose. Hence, the aim of this work was (i) to use computational simulations to further understand sucralose's lack of enzymatic reactivity and (ii) to synthesize the sucralose-based amphiphiles using conventional chemical synthesis and systematically study their tendency towards hydrogelation. Sucrose and sucralose were docked with a high-resolution atomic structure of lipase B from Candida antarctica, modeling the esterification transition state with an active site serine. In extended molecular dynamics simulations, sucrose remained in the active site due to multiple sugar-protein hydrogen bonds. The oxygen-to-chlorine substitutions in sucralose disrupted this hydrogen bonding network. Consistent with observed lack of enzymatic conversion, in multiple simulations, sucralose would rapidly dissociate from the active site. The sucralose-based LMWGs were subsequently synthesized using base-catalyzed conventional chemical synthesis. Three of the sucralose-based amphiphiles (SL-5, SL-6 and SL-7) proved to be successful hydrogelators. The gelators also showed the ability to gel selected beverages. The LMWGs gelled quantities of water and beverage up to 71 and 55 times their weight, respectively, and remain thermally stable up to 144 °C.
三氯蔗糖与蔗糖的区别仅在于其三个 Cl 基团取代了 OH 基团。它具有吸引人的特性，包括无热量、非致龋性、比蔗糖甜约 600 倍、在高温/酸性 pH 值下稳定、且无不良余味。这些特性使其成为食品添加剂的理想选择，其中之一是通过使用三氯蔗糖衍生的低分子量凝胶剂 (LMWG) 进行分子凝胶化技术获得的水凝胶。这种水凝胶对温度等外部刺激高度敏感，因为 LMWG 通过非共价相互作用自组装，因此可用于控制释放等应用。我们发现三氯蔗糖在脂肪酶生物催化下不反应，而蔗糖则不然。因此，这项工作的目的是：（i）使用计算模拟进一步了解三氯蔗糖缺乏酶反应性；（ii）使用常规化学合成合成基于三氯蔗糖的两亲物，并系统地研究它们形成水凝胶的倾向。将蔗糖和三氯蔗糖与来自南极假丝酵母的高分辨率脂肪酶 B 原子结构对接，模拟具有活性位点丝氨酸的酯化过渡态。在扩展的分子动力学模拟中，由于多个糖-蛋白氢键，蔗糖仍留在活性部位。三氯蔗糖中的氧-氯取代破坏了这种氢键网络。与观察到的缺乏酶转化一致，在多次模拟中，三氯蔗糖会迅速从活性部位解离。随后使用碱催化的常规化学合成合成基于三氯蔗糖的低分子量凝胶剂。基于三氯蔗糖的三种两亲物（SL-5、SL-6 和 SL-7）被证明是成功的水凝胶剂。凝胶剂还显示出凝胶选定饮料的能力。LMWG 将水凝胶化的量和饮料凝胶化的量分别达到其重量的 71 倍和 55 倍，并且在高达 144°C 的温度下仍保持热稳定。
