自由基加成反应及其在开发体内止血材料中的应用

发布时间：2018-05-29 02:35

本文选题：微创止血 + 自由基加成　；参考：《广州医科大学》2017年硕士论文

【摘要】：自由基加成反应在紫外光固化中非常重要。裂解型光引发剂在紫外光照射下跃迁至激发态,从而均裂生成自由基。苯甲酰自由基是常见的光解产物,其通过加到丙烯酸酯单体上,形成初级自由基,继而引发聚合反应。目前对于自由基加成反应的研究多集中于动力学方面,而基于过渡态理论,从能量、反应速率等方面对自由基加成反应进行的理论研究较少,把自由基加成反应结合到生物止血材料的研究也没有相关文献报道。本论文在第一章从密度泛函角度研究出发,研究苯甲酰自由基与戊烯、烯丙基甲基醚、丙烯酸甲酯三个单体的自由基加成反应。通过能量与构象变化分析,发现丙烯酸甲酯的活化能是三个反应体系中最小的,这是由于具有较小的形变能引起的。而戊烯与烯丙基甲基醚单体却因具有相似的形变而导致它们的形变能相近。通过自由基与烯烃单体的相互作用来揭示自由基加成反应的机理,并且通过弱相互作用的可视化加以证明其存在。弱相互作用分析研究发现三个反应体系的弱相互作用都来源于末端C12-C14,丙烯酸甲酯的Spike值是三个反应体系中最高的。通过键级曲线图描绘了旧双键断裂,以及新键形成过程。成键指数表明,丙烯酸甲酯反应体系的过渡态是“早期”过渡态,可以更早的形成反应复合物,导致活化能较小。最后通过电荷分析确定单体的活性,并通过反应速率进一步证实丙烯酸甲酯反应体系具有最小的活化能,反应速率最快。体内的止血是微创手术成功与否的关键之一。固体止血材料由于流动性差不能通过微创手术器械鞘管喷射进入体内,液体止血材料由于附着力低而导致无法粘附在组织。为了解决流动性和粘附性的矛盾,在第二章我们以自由基加成反应为理论依据,利用光引发剂与蔗糖单体在紫外照射下迅速固化成膜来实现止血。通过量子化学计算化学反应势垒、实时红外模拟体外成膜、动物实验观察止血效果、细胞实验考察原料细胞毒性等多方面实验,考证了含有烯丙基蔗糖醚单体(SAE)和α-羟基酮引发剂(HMPP)混合配方作为新型止血材料的可行性。从密度泛函理论证实了SAE与HMPP属于自由基加成反应,并具有所需的能量势垒较小、反应时间较短的优点。粘度实验和细胞毒性实验表明,该配方具有一定的流动性、毒性相对低的优点。虽然实时红外的结果显示最终转换率不高,但是体内止血实验证实了SAE与HMPP混合材料在50秒内就能在体内成膜止血,并且不受血流量的影响。在微创止血方面较其他止血材料具有竞争优势。为了更好的探讨光引发剂的光学特性,在第三章我们采用波函数分析方法研究新型肟酯引发剂的激发能量、分子轨道、电子跃迁密度矩阵。通过分子轨道研究发现OXE-1的能量带隙比OXE-2小,反映了前者较后者易激发。电子跃迁密度矩阵图显示了OXE-1和OXE-2从基态跃迁到激发态主要都是苯环和羰基上的电子跃迁引起的。比较激发能可以知道单线态的激发能和重组能都大于三线态,说明两者的电子结构在单线态时比三线态更稳定。并且OXE-1与OXE-2具有相似的垂直激发能,说明两者的激发过程的势能面间隔相近。
[Abstract]:The free radical addition reaction is very important in UV curing. The splitting photoinitiator LEPs to the excited state under ultraviolet light, and then breaks the free radical. Benzoyl free radical is a common photolysis product. It is added to the acrylate monomer to form the primary free radical and then initiates the polymerization. At present, the free radical addition is added to the free radical. The study of reaction is mostly focused on the dynamics, and based on the transition state theory, there are few theoretical studies on the addition reaction of free radicals from energy, reaction rate and so on. There is no related literature to study the combination of free radical addition reaction to biological hemostat. The free radical addition reaction of benzoyl radical with amyl, allyl methyl ether and methyl acrylate three monomers. Through the analysis of energy and conformation changes, it is found that the activation energy of methyl acrylate is the smallest in the three reaction systems, which is due to the smaller deformation energy. The mechanism of free radical addition reaction is revealed by the interaction between the free radical and olefin monomer, and the existence of the weak interaction is proved by the visualization of the weak interaction. The weak interaction analysis found that the weak interaction of the three reaction systems came from the end C12-C14 and the acrylic acid. The Spike value of methyl ester is the highest in the three reaction systems. Through the bond grade curves, the fracture of the old double bond and the formation of the new bond are depicted. The bond index indicates that the transition state of the methyl acrylate reaction system is a "early" transition state, and the reaction complex can be formed earlier, and the activation energy is smaller. Finally, the single charge activation energy is small. Finally, the charge analysis is used to determine the monomer. The activity of the body and the reaction rate further confirm that the methyl acrylate reaction system has the smallest activation energy and the reaction rate is the fastest. The hemostasis in the body is one of the keys to the success of minimally invasive surgery. The solid hemostat can not be injected into the body by the minimally invasive surgical instrument sheath, and the liquid hemostat is attached to the body because of poor fluidity. In order to solve the contradiction between fluidity and adhesion, in order to solve the contradiction between fluidity and adhesion, in the second chapter, we use the free radical addition reaction as the theoretical basis, using the photoinitiator and the sucrose monomer to rapidly solidify into the membrane to achieve the hemostasis. In animal experiments, the effect of hemostasis was observed, and the cytotoxicity of raw material cells was examined by cell experiments. The feasibility of the mixture of Xi Bingji sucrose ether monomer (SAE) and alpha hydroxy ketone initiator (HMPP) as a new type of hemostat was tested. The density functional theory proved that SAE and HMPP are free radical addition reactions and have the required energy. The viscosity test and cytotoxicity test showed that the formula had a certain fluidity and relatively low toxicity. Although the real-time infrared results showed that the final conversion rate was not high, the internal hemostasis experiment in the body confirmed that the SAE and HMPP mixture could be hemostasis in the body within 50 seconds in the body. In order to better investigate the optical properties of photoinitiators, in the third chapter, we use wave function analysis to study the excitation energy, molecular orbital and electron transition density matrix of new oxime initiators in the third chapter. The energy band gap is smaller than that of OXE-2, which indicates that the former is easier to be excited than the latter. The electron transition density matrix diagram shows that the transition from the ground state to the excited state from the ground state to the excited state is mainly caused by the electron transition on the benzene ring and the carbonyl group. The excitation energy and the recombination energy of the single state can be known to be greater than the three linear state, indicating the electronic structure of the two. The singlet state is more stable than the three line state, and OXE-1 and OXE-2 have similar vertical excitation energy, indicating that the potential energy interval between them is similar.
【学位授予单位】：广州医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R318.08

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