Research On Drug Molecular Structure Based On Raman Spectroscopy

The efficacy of a drug is related to its conformation and chiral characteristics.The mechanism of action between drug and protein can be obtained by identifying the conformation isomerism of drug molecules interacting with biological proteins,and the chiral purity of drug molecules can be detected in drug preparation by identifying the chiral differences of drug molecules.In the conformational research of drug molecules,they all need to be based on a physiological environment,which is usually a liquid state with various biological macromolecules.However,most of the existing detection methods cannot achieve in-situ measurement of samples in a liquid environment.The method that can be detected in a liquid environment will cause the overlapping and annihilation of signals because the protein molecular weight is too large.In the detection of chiral purity of drug molecules,it is required that the detection can provide structural information and be convenient and fast.However,most of the detection methods currently in use require either complex sample processing or longer signal acquisition times.Therefore,fast detection is not possible.In order to solve these problems,a kind of detection method based on Raman spectrum is proposed in this paper.The conformation characteristics of drug molecules were detected by Raman C-H/C-D stretching vibration spectrum,and the chiral purity of drug molecules was detected by Raman spectroscopic method.These two methods are proposed for the first time in this paper.These two detection methods will be used to specifically solve the following problems:(1)Raman C-H/C-D stretching vibrational spectroscopy was used to detect the microstructure of MA molecules in solid RS-MA,solid R-MA and RS-MA aqueous solutions.Using MP2 method and selecting the 6-311+G(d,p)basis set to obtain the mandelic acid rotamer and the corresponding theoretical Raman spectrum.Among them,the C-D stretching vibration spectrum peak completely avoids the overlapping area of the biological macromolecule peaks,and the C-H/C-D stretching vibration spectrum is very sensitive to the mandelic acid molecular structure.Comparing the theoretical results with experimental spectra,the structural difference between solid RS-MA and solid R-MA is the trans and non-trans conformations of CH and-OH,which is consistent with the results of X-ray diffraction.CH and-OH in mandelic acid aqueous solution are in non-trans conformation,and the carboxyl group is in cis structure.The carboxyl group is approximately perpendicular to the C-benzene bond,and the benzene ring is approximately coplanar with Ca-H.(2)The Raman vibrational spectrum resolution method is used to detect the enantiomeric excess(ee)value of solid MA melted and cooled.First,based on the Raman spectra of solid RS-MA and solid R-MA melted and cooled,the-OH stretching vibration spectrum was selected as the detection interval.Raman spectra of solid MA with ee values ranging from 0%to 100%were collected in the interval of 10%.The decomposition of these spectra proved that the-OH stretching vibration spectrum of MA molecules with any ee value contains two sets of spectral components.That is,the spectrum characterizing the RS interaction and the spectrum characterizing the RR type interaction.Integrating the intensity of the two sets of spectra,the ee value can be obtained.In this experiment,ten MA samples with different ee values were estimated,and the errors were less than 5%...