Nuclear Magnetic Resonance Method For Screening Trace Sulfur Mustard Compounds In Complex Sample Matrix

Sulfur mustard compounds poses a great threat to national security and social safety,and the actual screening environment is complex and varied.In this study,~1H NMR and one-dimensional selective excitation were used for non-destructive screening of sulfur mustard compounds in complex samples.A systematically research was carried out by studying the influence factors of chemical shift,optimizing the one-dimensional selective excitation methods,designing a reasonable screening program and creating NMR spectra database for automatically searching.The main research contents and conclusions are as follows:(1)The study on ~1H NMR chemical shift of sulfur mustard compounds.Bis(2-hydroxyethyl)sulfide was selected as the model compound to study the influencing factors of chemical shift.The factors including solvents,concentrations,p H and ionic strength influenced on the chemical shift were researched,and the main influence comes from the solvent effect.The characteristic ~1H NMR chemical shift of Bis(2-hydroxyethyl)sulfide in most kinds of solvent ranged from 2.519 to 2.795 ppm for SCH2,and from 3.484 to 3.814 ppm for CH2OH,except for deuterium pyridine and deuterium benzene.To select the exciting position in the actual sample screening,it is necessary to determine the possible chemical shift range of the target characteristic peaks according to the solvent used in the sample.(2)Optimization of one-dimensional selective excitation experiment parameters.Bis(2-hydroxyethyl)sulfide was used as the model compound for the optimization of 1D TOCSY and 1D NOESY.Through calculation and experiments,Q3 shaped pulse was selected as the selective pulse and the basic parameters including the relaxation delay and mixing time were optimized:D1=9s for both 1D TOCSY and 1D NOESY,D8=1.5s for 1D NOESY and D9=0.04s for 1D TOCSY.Under the optimized conditions,the maximum correlation peak signal intensity is obtained while ensuring selectivity and avoiding phase distortion.(3)Comparative study of one-dimensional selective excitation methods.For the case of the target signals in mixture were covered in ~1H NMR spectrum,the performance of1D TOCSY,1D NOESY,1D CSSF-TOCSY and doubly selective STEP-NOESY were compared.The feasibility of 1D homonuclear selective excitation methods for blind excitation was proved.It has shown that the outstanding selective detection ability of the STEP-NOESY method.However,the detection sensitivity of STEP-NOESY is significantly lower than the traditional one-dimensional selective excitation methods,which cannot be applied in the trace analysis of sulfur mustard compounds.(4)Research on a high-sensitive one-dimensional double-selective excitation method.Considering the low sensitivity of STEP-NOESY,doubly selective 1D TOCSY-TOCSY was developed on the basis of pulse sequence of STEP-NOESY,and was used to screen the trace bis(2-hydroxyethyl)sulfide against high background.Under the optimized conditions,the signal to noise ratio of 5μg/m L bis(2-hydroxyethyl)sulfide met the identification criteria with 128 scanning numbers in 20 min,and 0.1μg/m L bis(2-hydroxyethyl)sulfide can be qualitative detected with 8000 scanning numbers in 12 h.The sensitivity of this method is 20 times higher than that of STEP-NOESY with the same selectivity.(5)Design and verification of sulfur mustard compounds screening scheme.The chemical shift distribution rules of characteristic groups of 37 sulfur mustard compounds were summarized.Using 1D TOCSY and 1D NOESY as detection methods,two screening schemes were designed based on the chemical shift ranges and characteristic groups of compounds separately.An organic sample contained 24 sulfur mustard compounds in CDCl3 and an aqueous sample contained 15 sulfur mustard compounds in D2O were prepared for the verification experiments.In these two extreme samples cases where multiple compounds with the similar characteristic groups coexist,the ~1H NMR spectra overlap severely.80～90%of the compounds could be distinguished and identified by grouping screening scheme.Four similar compounds of bis(2-chloroethyl)sulfide(Cl CH2CH2SCH2CH2Cl),bis(2-chloroethyl)disulfide(Cl CH2CH2SSCH2CH2Cl),bis(2-hydroxyethyl)sulfide(HOCH2CH2SCH2CH2OH)and bis(2-hydroxyethyl)disulfide(HO CH2CH2SSCH2CH2OH)were further identified by 1D TOCSY-TOCSY.(6)Establishment and verification of Assure NMR database of sulfur mustard compounds.An Assure NMR database was created with ~1H NMR and 2D HSQC data of39 sulfur mustard compounds in different solvents.A series of automatic searching could be achieved,however,the correct interpretation of match results has to be decided by the expert.It is helpful to efficiently screen sulfur mustard compounds in complex mixture with the automatic database searching.