Design And Theoretical Study Of Photoswitchable Anion Receptor

Photoswitches,which can undergo reversible photoisomerization under external light stimulation,are widely used in light response systems such as molecular motors,photopharmacology,and host-guest recognition systems and so on.The light-responsive anion receptor is an important branch in the host-guest recognition system.Organisms contain a lot of anions,and anions play an important role in organisms.Disorders of membrane protein functions involved in anion transport can cause many serious diseases.Synthetic anion receptors can replace defective natural transporters and are very good therapeutic drugs.A large number of artificial anion receptors have been developed.Among them,photoresponsive anion receptors can regulate when and where receptor molecules bind or release guest anions through light,and are widely used to develop photopharmacological drugs.At present,most of the photoresponsive anion receptors are based on azobenzene and rigid stilbene.Both of these two kinds of photoswitches have two defects:the bidirectional light conversion rates are not high and the thermal stability of the Z isomer is not good enough.Azopyrazole has its unique advantages in these two aspects.In addition,one of the important challenges faced by the application of photoswitches to living organisms is the need to use red light or near-infrared light that can penetrate tissues and is harmless to the tissues.The recently reported di-o-fluoro-di-o-chloro azobenzene can be triggered by red light and produce a high conversion rate under light steady state.The thermal stability of its Z isomer is also good enough.These excellent characteristics make it an ideal photoswitch for biological applications.Based on the azopyrazole and di-o-fluorodi-o-chloro azobenzene molecules,we have designed several different photoresponsive anion receptors.We theoretically studied the photoresponsive properties of these new molecules,including bidirectional light conversions and thermal half-lives of Z isomers,and their selectivity to anions as receptors.This dissertation is divided into four parts,as follows:The first chapter has four parts:part I introduces the importance of photoswitchable molecular systems;part II introduces the working mechanism of photoswitches,especially azobenzene and heteroaryl azo photoswitches;part III introduces the important applications of photoswitches,including molecular motors,photopharmacology,supramolecular host-guest recognition molecular systems;part IV introduces the development status of photoresponsive anion receptors.The second chapter introduces the theoretical methods used in my studies,including the first principle,density functional theory(DFT),time-dependent density functional theory(TD-DFT),Atom in Molecules(AIM)method and Independent Gradient Model(IGM)method and the software packages for quantitative calculation.The third chapter is about my first published work on azopyrazole-based photoswitchable anion receptor for dihydrogen phosphate transport.Based on the known 1-N-methyl-3-phenylazopyrazole(3pzH)photoswitch,a new type of tetra-formamide-3pzH(3pzH_TA)photoswitchable anion receptor was designed.Through the simulation of UV-vis absorption spectrum:3pzH_TA has high E→Z(>98%)and Z→E(97%)photoisomerization rates;based on the transition state theory,the thermal half-life of 3pzH_TA is two times longer than that of 3pzH.We calculated the binding affinities of E and Z isomers to TBA+and found that 3pzH_TA has high sensitivity to H2PO4-anion.Furthermore,the AIM method was used to reveal the key role of hydrogen bonds between H2PO4-and Z isomer in the binding complex.Our findings open up a new strategy for the rational design and understanding of new types of photoswitchable anion receptors.The fourth chapter is about my second work on computational design of photoswitchable anion receptors comprised of red-shifted and bistable di-ortho-fluoro di-ortho-chloro azobenzene derivatives.Photo-therapeutic applications require efficient photo-switchable anion receptor materials with high photoisomerization ratio,thermal stabilities,and apparent difference in binding affinities for anions by different isomers.Based on the di-ortho-fluoro di-ortho-chloro azobenzene(dfdc-AB)photoswitch,we designed three different photoresponsive anion receptors:four-formamide-di-ortho-fluoro-dfdc-AB(dfdc-AB-CH3),tetra-fluoromethyl-formamide-dfdc-AB(dfdc-AB-CF3)and four methoxy-formamide-dfdc-AB(dfdc-AB-OCH3).By the simulated absorption spectrum and transition state theory calculation,we found that dfdc-AB-OCH3 has nearly bistability,high E→Z conversion in the visible region,and apparent difference in binding affinities for CH3CO2-by different isomers,indicating a promising photoresponsive anion receptor in photopharmacology.The fifth chapter is about the summaries and outlooks of my work.There are three main innovations in my work:(1)Based on good performance photoswitches,3pzH and dfdc-AB,the new photoresponsive anion receptors,such as 3pzH_TA and dfdc-AB-CH3,dfdcAB-CF3 and dfdc-AB-OCH3,are designed.(2)Taking the core molecules 3pzH and dfdc-AB as the references,three standards are used to evaluate the efficiency of photoresponsive anion receptors:E and Z light conversion rates are high,Z isomers have good thermal stability,and the binding energies of different isomers to anions are large and the difference is obvious.(3)3pzH_TA not only has bistability and high bidirectional conversion rates,but also has obvious selectivity to H2PO4-;dfdc-AB-OCH3 has bistability,is expected to produce high E by red light and has obvious selectivity to CH3CO2-.Both of these molecules are promising photoresponsive anion receptors.We will also conduct follow-up research from the following three aspects;(1)Seek cooperation with the experimental team,including:synthesizing molecules;measuring ultraviolet-visible absorption spectra;doing 1HNMR titration experiments;measuring the influence of anions on the photoresponsive properties of the receptors.(2)Looking for photoswitches and modified groups with better performance.(3)Carry out kinetic simulation calculation to study the kinetic process of thermal reactions and the influence of solvent.