利用密度泛函理論探討碳鏈長度對對甲基吡啶羧基甜菜鹼周圍水分子氫鍵網路的影響

Carbon Spacer Length Effect on Hydrogen Bond Networks near 4-Methylpyridine Carboxybetaine in Aqueous Environment by Density Functional Theory Calculations

梁宇睿(Yu-Jung Liang)

指導教授 ： 林子仁

中原大學/工學院/化學工程研究所/碩士(2021年)

https://doi.org/10.6840/cycu202100252

摘要

兩性離子型分子材料(zwitterionic)是具有抵擋蛋白質吸附，水合能力優異等多樣優點的抗沾黏材料。常見的兩性離子型分子有phosphobetaines (PBs), carboxybetaines (CBs) 及 sulfobetaines (SBs)。它們對於水分子均擁有高度的親和力，因此它們能在材料表面上形成水層以避免其他生物分子如蛋白質的吸附。根據以往的研究結果來看，兩性離子型分子的陰陽離子間的碳鏈長短會影響水合能的大小。
此次研究的目的是採用量子化學計算及分子動力學探討針對對甲基吡啶羧基分子(4Methylpyridine Carboxybetaine, 4MPCB)的碳鏈長短對水合能力的影響。以碳鏈數為一、二、三及四的4MPCB分子作為此研究的研究對象。首先，先採用密度泛函M062X對4MPCB分子進行結構優化並計算各碳鏈下的pKa。接著採用混合溶劑化模型，在各碳鏈下的4MPCB分子的周圍隨機分佈15顆水分子且同時生成50種不同的初始結構，爾後採用半經驗法，密度泛函PBE及M062X逐步篩選出低能量的構型。最後，使用分子動力學分析各碳鏈下的4MPCB分子及質子化4MPCB分子的氫鍵網路。
根據研究結果發現，4MPCB分子偏好以間扭的構型存在於水環境中。4MPCB分子的pKa隨碳鏈數增加而升高。4MPCB分子的陰離子集團相較於陽離子集團更容易吸收周圍的水分子，因為陰離子的電負度較大。透過分子動力學的結果可以知道，碳鏈數三及四的4MPCB分子由於碳鏈的柔軟度造成碳鏈彎曲，受陰離子吸引的水分子會受到來自陽離子方向的影響進而減弱了陰離子對水分子的吸引力，導致氫鍵網路較鬆散，而當碳鏈數為一時的4MPCB分子則是因為陰陽離子間的距離是四者最短，偶極距較小而使吸引水分子的能力較弱。然而，當碳鏈數為二時的4MPCB分子因為適中的碳鏈長度，將水分子都滯留於陰離子周邊，不易受陽離子的影響，形成較為緊密的氫鍵網路。

關鍵字

密度泛函理論 ； 兩性離子分子 ； 碳鏈長度

並列摘要

Zwitterionic molecules such as phosphobetaines (PBs), carboxybetaines (CBs) and sulfobetaines (SBs) have great potential for nonfouling materials that prevent protein adsorption because of their high water hydrations. Water forms a strong hydration layer on the material surfaces to prevent organic foulant molecules from adsorbing. Recent experiment results showed that the carbon spacer length (CSL) between cation and anion groups of zwitterionic molecules influenced the water affinity.
In this study, we used quantum chemistry and molecular dynamics simulations to investigate the CSL effect on water hydrations of 4-Methylpyridine Carboxybetaine (4MPCB). First, M062X was used to optimize the structures and calculate the pKa with different CSL – n in which n is equal to 1, 2, 3, and 4. Second, we spread 15 water molecules around 4MPCB molecule and generated 50 different initial random structures. Then we screened out lowenergy structures and analyzed hydrogen bond network with deprotonated and protonated system in aqueous environment by quantum chemistry and molecular dynamics.
The results showed that 4MPCB molecule prefer gauche configuration in aqueous environment. From the pKa calculations, the pKa become higher when CSL become longer. Besides, the anion group was easier to gather water molecules than the cation group because the anion group has a greater electronegativity. According to the results of molecular dynamics, we found that the carbon chain became bending as CSL increased because of the flexibility in CSL3 and CSL4. Water molecules followed the anion group and approach to the cation group. Cation group decreased the attraction of anion group to water molecules, resulting in a loose hydrogen bond networks. Short CSL like CSL1 had a loose hydrogen bond networks because of low dipole moment. CSL2 had moderate CSL, so the cation group did not affect the anion group. In addition, the pyridine pure excluded the water molecules and they were attracted fully by the anion group. In this regard, CSL2 showed the strongest hydrogen bond network. The calculation results are consistent with experiment observation.

並列關鍵字

Density Functional Theory ； Zwitterionic ； Carbon Spacer Length

參考文獻

1. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B., et al. Gaussian 16 Rev. C.01, Wallingford, CT, 2016.

2. Singer, S. J.; Nicolson, G. L., The Fluid Mosaic Model of the Structure of Cell Membranes. In Membranes and Viruses in Immunopathology, Academic Press, 1972, 7-47.

3. Hench, L. L.; Ethridge, E. C., Biomaterials: An Interfacial Approach. Academic Press, New York, 1982.

4. Williams, D. F., Definitions in Biomaterials: Proceedings of a Consensus Conference of the European Society for Biomaterials. Chester, England, 1987.

5. Shi, D., Introduction to Biomaterials. Tsinghua University Press, China, 2006.