Department of Chemistry, University of Delhi, Delhi-110007, India.
Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Phys Chem Chem Phys. 2020 Mar 4;22(9):5301-5313. doi: 10.1039/c9cp06683g.
Biomedical industries are widely exploring the use of thermo-responsive polymers (TRPs) in the advanced development of drug delivery and in many other pharmaceutical applications. There is a great need to investigate the use of less toxic and more (bio-)compatible TRPs employing several additives, which could modify the conformational transition behavior of TRPs in aqueous solution. To move forward in this aspect, we have chosen the less toxic bio-based polymer poly(N-vinylcaprolactam) (PVCL) and three different methylamine-based osmolytes, trimethylamine N-oxide (TMAO), betaine and sarcosine, in order to investigate their particular interactions with the polymer segments in PVCL and therefore the corresponding changes in the thermo-responsive conformational behavior. Several biophysical techniques, UV-visible spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS) and laser Raman spectroscopy, as well as classical computer simulation methods such as molecular dynamics are employed in the current work. All the studied methylamines are found to favor the hydrophobic collapse of the polymer thus stabilizing the globular state of PVCL. Sarcosine is observed to cause the maximum decrease in lower critical solution temperature (LCST) of PVCL followed by TMAO and then betaine. The differences observed in the LCST values of PVCL in the presence of these molecules can be attributed to the different polymer-osmolyte interactions. The less sterically hindered N atom in the case of sarcosine causes a significant difference in the phase transition temperature values of PVCL compared to betaine and TMAO, where the nitrogen atom is buried by three methyl groups attached to it.
生物医学行业正在广泛探索使用温敏聚合物 (TRP) 来推进药物输送的先进发展，并应用于许多其他制药领域。非常有必要研究使用毒性更低、生物相容性更好的 TRP，并采用几种添加剂来改变 TRP 在水溶液中的构象转变行为。为了在这方面取得进展，我们选择了毒性较低的生物基聚合物聚 (N-乙烯基己内酰胺) (PVCL) 和三种不同的甲胺类渗透剂，三甲基氧化胺 (TMAO)、甜菜碱和肌氨酸，以研究它们与 PVCL 中聚合物链段的特殊相互作用，以及相应的温敏构象行为变化。目前的工作采用了多种生物物理技术，如紫外可见光谱、荧光光谱、动态光散射 (DLS) 和激光拉曼光谱，以及经典的计算机模拟方法，如分子动力学。所有研究的甲胺都有利于聚合物的疏水塌陷，从而稳定 PVCL 的球状状态。结果表明，肌氨酸导致 PVCL 的最低临界溶液温度 (LCST) 下降最大，其次是 TMAO，然后是甜菜碱。在这些分子存在下，PVCL 的 LCST 值观察到的差异可归因于不同的聚合物-渗透剂相互作用。在肌氨酸的情况下，由于氮原子的空间位阻较小，与甜菜碱和 TMAO 相比，PVCL 的相变温度值存在显著差异，其中氮原子被与其相连的三个甲基基团所掩盖。
