Spectroscopic Study Of Chiral Interactions Between Amino Acids, Drug Molecules And Nano-precious Metals

Many substances in life are chiral and it is important to differentiate between chiral substances as they often exist as a single enantiomer to achieve high efficacy and reduced dosage.The key to chiral discrimination is to amplify the difference between enantiomers and to convert this difference into a measurable optical signal.One effective means of amplifying enantiomeric differences is through the interaction of chiral molecules with other chiral molecules or nanomaterials.Surface-enhanced Raman spectroscopy(SERS)has the advantages of high Raman scattering and sensitivity to intermolecular interactions,but the SERS signal differences between enantiomers are small.Therefore,the amplification of difference in SERS spectra between enantiomers is a key issue to prompt the broad usage of SERS spectroscopy.A pair of enantiomers shows opposite circular dichroism(CD)signals,and therefore CD spectroscopy can directly identify enantiomers.However,the CD signal is weak and poorly differentiated when the concentration of the substance is low.Consequently,it is of importance to develop suitable methods to enhance the CD signals.In this study,precious metal nanoparticles are used as SERS substrates,chiral interactions between amino acids and chiral drug molecules are used to amplify the SERS signal difference between enantiomers and achieve chiral differentiation,and the mechanism of the interaction between chiral amino acids and chiral drugs is analyzed with theoretical simulations.At the same time,these precious metals can also interact with amino acids,resulting in a significant enhancement of the CD signal of amino acids and facilitating the detection of low concentrations of amino acids by CD spectroscopy.This study is divided into three parts:1.In the second chapter,chiral SERS substrates were prepared by modifying amino acids(phenylalanine or Cysteine)on the surface of silver-coated gold nanorods(Au@Ag nanorods).Since amino acids enantiomers were not distinguished by SERS spectroscopy,chiral drug-amino acid interactions were introduced.Firstly,after the addition of the chiral drug sertraline,there was a significant difference in the SERS signal enhancement between the D-phenylalanine and L-phenylalanine,leading to differentiation of the phenylalanine enantiomers.Secondly,the effect of sertraline on the conformation of D-and L-type phenylalanine was significantly different,and the mechanism of enantiomeric discrimination was explained by theoretical simulation calculations.Thirdly,the effect of thicknesses of silver layers on the chiral discrimination was investigated,and it was found that only silver-coated gold with an appropriate silver layer thicknesses showed the best discrimination effect.2.In order to investigate the chirality-selective interaction between the two chiral drug enantiomers and the amino acid enantiomers,in the third chapter,we investigated the differences in SERS spectra between amino acid enantiomers after the addition of propranolol.Firstly,the addition of R-propranolol enantiomer to Au@Ag-D-Cys reduced the SERS signal of D-Cys by 86%,whereas the decrease is only 33% after the addition of S-propranolol.The enantiomers of propranolol were distinguished by the above different changes in SERS signals.Secondly,cysteine enantiomers modified on Au@Ag nanorods could not be distinguished propranolol.Thirdly,phenylalanine enantiomers modified on silver-coated gold could not be discriminated by the addition of propranolol.3.In the fourth chapter,chiral interactions between amino acids and nanoparticles were investigated by using circular dichroism spectroscopy to amplify the CD signal.Firstly,compared with the CD signal of pure cysteine,the CD signals of cysteine were enhanced up to 133-fold in the presence of silver-coated gold nanorods.Secondly,chiral transfer may exist between cysteine and silver-coated gold nanorods,because the CD signals for Au@Ag-Cys are obviously different from those of cysteine.In addition,the chiral transfer and CD signals amplification above are also found when silver nanoclusters and Au@Ag nanorods with a thicker silver layer was used.Thirdly,the CD signals amplification(up to 9-fold)of phenylalanine by Au@Ag nanorods was also found,but the chiral transfer between phenylalanine between Au@Ag nanorods is not obvious.