Mechanochemistry Studies And Applications On Thiol-Double Bond Michael Addition Reaction

Mechanochemistry,where chemical conditions are induced by mechanical force,is different from traditional chemical classifications such as photochemistry,electrochemistry,and thermochemistry.It plays an increasingly important role in biochemical synthesis,drug design,surface processing and other more research areas.However,as a young discipline,mechanochemistry still has many unknown areas waiting to be explored and challenges to be conquered.In this Master’s thesis,we specifically selected several Thiol-Double bond Michael addition reaction chemical systems,hoping to explore the mechanochemical pathways.Such reaction systems rages from single-molecule mechanics to macro-mechanical manipulation,based on which we shall make a few applicants.In chapter 1,we started with the definition and development of mechanochemistry,and introduced several single-molecule and macroscopic mechanochemical research methods in detail.Furthermore,we briefly introduced the development and advances of Dip-Pen Nanolithography(DPN)and several techniques derived from it.The deficiencies and developing prospects of the combination of DPN and the mechanochemical reaction system were discussed at the last.In Chapter 2,we focused on the Michael addition reaction products of ThiolMaleimide.This structure had two chemical transforming pathways: the retro-Michael dissociation and the ring-open hydrolysis.Some preliminary SMFS studies had pointed out that mechanical traction could significantly accelerate the hydrolysis of ThiolMaleimide conjugation and led to a more stable covalent compound.Based on the existing research results and inferences,we used the cavitation effect generated by ultrasonic oscillation to stretch the polymer chain which had Thiol-Maleimide conjugates within and made chemical characterization for them.Furthermore,we designed a group of antibody-drug conjugates by using former mechanochemical setup to induce ring-open hydrolysis,and successfully developed the application where we used mechanochemical pathway to enhance the conjugates to improve chemical compound stability in life environment.In Chapter 3,we took the advantage of mechanochemistry’s high simplicity and low pollution to explore a new chemical reaction pathway that induces the addition of Thiol-Acrylamide under mechanical pressure.After appropriate chemical modification design,pressure was applied between the scanning probe and substrate of the atomic force microscope.Then we successfully initiated the Michael addition reaction of Thiol-Acrylamide,where single molecular event was labeled by the unfolding of the polyethylene glycol(PEG)polymer chain.On the macro scale,high-speed mechanical extrusion was applied to the mixture of small molecule acrylamide and thiol.We finally made an application of mechanochemical synthesis using ball-milling technology.In Chapter 4,based on our understanding of the dissociation strength of chemical bonds in SMFS experiments,we used a pair of weak chemical bonds to generate chemical adsorption so that the flux of force-dependent Michael addition reaction between thiol and butene got increased on the pressing position between model substrate and the paper substrate.We successfully developed a derivative DPN techniques based on mechanochemical reaction system.