Synthesis Of Artificial Metalloenzyme Based On Serum Albumin And Asymmetric Oxidation Of Sulfides

Optically active sulfoxides are useful building blocks as intermediates and auxiliariesin organic synthesis.They are also constituted important biologically active compounds in the pharmaceutical industry.To date,the asymmetric oxidation of corresponding prochiral sulfide is the most powerful and reliable route.Endeavoring to guide principles of green chemistry and sustainable development of industry,exploring the "high efficiency low energy" and green friendly" of catalytic system has become the research hotspot in the field of chemistry.During the past few decades,Artificial metalloenzymes-a promising new kind of eco-compatible hybrid biocatalysts,represents anattractive alternative for enantioselective catalysis due to have the advantages of homogeneous catalyst and natural enzyme.They are able,like enzymes,to work under mild conditions with high activity.However,the metalloenzymes using H2O2 as oxidant generally display low activity and overoxidant in asymmetric sulfide oxidation.Continue to synthesize efficient artificial metalloenzymes under the environment-friendly conditions remainschallenge.In this thesis,due to good catalytic activity of Salen complex,six Salen complexes(ML1)were synthesized from hydrothermal method of salen ligand H2L1(H2L1=bis(a-ethyl-salicylaldehyde)ethylenediiminato),and were characterized by IR,Elemental analysis,MS and X-ray.Only artificial metalloenzymes(BSA-CoL1,HSA-COL1)based on the incorporation of CoL1 complexwith bovine serum albumin(BSA)and human serum albumin(HSA)have been synthesized,and characterized by UV-visible and molecular docking,revealing the presence of interaction between the CoL complex and the BSA and the BSA is able to bind one CoL and CoL molecule is inserted into the hydrophobic cavity of subdomain IB(site I)of BSA.Studing on the interaction between MLi and BSA.Fluorescence spectroscopy demonstrates binding of CoL1withBSA was the strongest,which is constant with catalytic active.Thesecondary structure and the amino acid residues microenvironment of BSA have change in the presence of these complexes.SA-CoL1 is the first time theintroductionof Co-salen complex into serum albumins.BSA/HSA-CoLiwere used as biocatalyst for asymmetric sulfoxidation of thioanisole(PhSMe,a model substrate).The influence of parameters through optimizing reaction conditions was studied using thioanisole as a model substrate in the presence of "green oxidant",H2O2.Comparing SA and CoL1,BSA/HSA-CoL1 can catalyze the sulfoxidationaffording higher enantiomeric excess by H2O2.The influence of parameters through optimizing reaction conditions was studied.The ratios of H2O2:PhSMe:BSA-CoL1(2.7 ?mol)were 150:100:1;substrate concentration;1.35 mmol/L;substrate mixing time:5 h;temperature:0?;H2O2 was added in four portions;in the absence of co-solvent;reaction time:28 h.Over-oxidation to sulfone was either entirely absent or very minimal in most cases.The oxidative kinetic resolution of the product is either not occurring or negligible.Under optimum conditions,BSA-CoL1 is efficient for the enantioselective oxidation of a series of sulfides,producing corresponding sulfoxides in excellent conversion(up to 100%),chemoselectivity(up to 100%)and good enantiomeric purity(up to 87%ee)in certain cases.Binding of complex 1 with the serum albumin was characterized by UV-visible.In the presence of BSA,the optimum pH and oxidant for ML1(MnL1?CoL1?FeL1?CuL1)systems are 4.7 and TBHP except 5.1 and H2O2 for VL1system.Comparing the reaction results of SA,ML,and ML,in the presence of SA,SA could promote the catalytic active of ML1.Vinyl phenyl sulfoxide obtains the highest ee value(94%)by TBHP at pH 4.7 using HSA/VL1 system.Increasing the interaction of the metal complex with the protein leads to better enantioselectivities.CoL1 artificial metalloenzyme is functionally equivalent to BSA-CoL1 in the presence of BSA.Five Salan complexes(ML2)based Salphen ligand H2L2(H2L2=3,4-bis((2-hydroxynaphthalen-1-yl)methyleneamino)benzenesulfonic acid which has been synthesized before were use as catalyst for enantioselective oxidation of a variety of sulfides.The influences of the parameters(pH,oxidant,concentration of catalyst/oxidant/substrate on the thioanisole as model are investigated.BSA-CoL2/MnL2/CrL2afford higher catalytic active by H2O2 in PB(pH 5.1).Whereas BSA-VL2/FeL2afford higher catalytic active by TBHP in PB(pH 8.0).Under optimum conditions,ehemoselectivity washigh(>90%)in all cases.BSA-FeL2,BSA-VL2 and BSA-CoL2aflord the best conversion,chemoselectivity and enantiomeric purity,respectively.Comparing BSA-CoL1,BSA-CoL2 which contain the more hydrophilicCoL2performs inferior catalytic activity and enantioselectivity.BSA-VL2/FeL2 afford 94%and 96%ee for the sulfoxidation of 4-Methoxyphenyl methyl sulfoxide and 4-Bromophenyl methyl sulfoxide,respectively.SA also promote the catalytic active of V?8?.V?8 afford74%and 68%ee for the sulfoxidation of Methyl phenyl sulfoxideand 4-Methoxyphenyl methyl sulfoxide in the presence of BSA and PSA,respectively.The enantioselectivity is associated with the binding strength between complexand SA whether large or small molecules.