J . Phys. Chem. 1994,98, 3669-3674
3669
Conformational Analysis of Sulfur Mustard from Molecular Mechanics, Semiempirical, and ab Initio Methods William H. Donovan. and George R. Famini US.Army Edgewood Research; Development and Engineering Center, SCBRD- RTC, Bldg. E3160, Aberdeen Proving Ground, Maryland 21010-5423 Received: October 6, 1993; In Final Form: February 10, 1994’
We report the results of a comprehensive computational investigation on the energetics of sulfur mustard (S(CH2CHZC1)2) conformations. Molecular mechanics (MM2*, MM3*, AMBER*, and OPLS*), semiempirical (MNDO, AM1, and PM3), and ab initio (HF/3-21G, HF/6-31 lG**, MP2/6-31G*, and MP2/6-311G**/ /HF/6-3 1lG**) methods were applied to 12 low-energy structures obtained from a Monte Carlo conformational search using force fields contained in MacroModel 3.5a. In general, there is reasonable agreement between molecular mechanics and ab initio for geometrical properties, but significant differences in the energy predictions. There was more scatter from thesemiempirical computations, with the AM 1 model most successfully reproducing the ab initio results. The ab initio calculations identify at least three conformations of sulfur mustard lower in energy than the all-anti structure, depending on the level of theory employed. Vibrational infrared spectra were computed for the four lowest energy structures at the HF/6-3 11G** level and compared to experimental data, producing a better match than obtained from consideration of a single conformer, but at greater computational cost.
Introduction Due to its use as a potent chemical warfare agent, 2,2’dichlorodiethyl sulfide (sulfur mustard, HD) has been the subject of numerous studies by scientists of several different disciplines since World War 1.1 Despite this scrutiny, the interactions between HD and biological systems still defy sufficient understanding. Sulfur and nitrogen mustards are often described as bifunctional alkylating agents capable of cross-linking DNA,14 but they are also known to react with many other molecules of biological importance.ls4 Thus, little progress toward effective antidotes or pretreatments has been forthcoming, and current medical therapies are primarily limited to symptomatic treatments. This situation is in contrast to the impressive medical strides made against nerve agents for which antidotes and pretreatments are both available and effective when vigilantly employed. Nevertheless, much useful information has been gained from these HD studies, and as more is learned about the chemistry involved, the chances of intervening effectively to mitigate HD’s incapacitating effects are increased.’ While the large number of substrates present in biological systems makes understanding their chemistry with HD a daunting task, recent progress has been realized in the study of the decontamination reactions of HD, and other chemical warfare agentsas One of the essential features contributing to the unique chemistry of HD, as opposed to the traditional chemistry expected from alkyl halides, is its ability to form a cyclic sulfonium ion intermediatethrough anchimericassistancefrom the sulfur atom, resulting in displacementof a chloride The episulfonium ion thus formed is thought to be an energetic species, capable of facile reactions with nearby molecules. Because of its relatively small size and potential for undergoing complex reactions with many other substances, HD is also an attractive compound for modeling studies. Although the literature contains reports of computational studies on sulfur mustard, they include only cursory treatments of mustard‘s conformationalpreferences4J416or were conducted using a simplified model of questionable reliability17 for a molecule containing sulfur and chlorine atoms such as HD. Modern computationaltechniquesnow include effective methods for evaluating the conformational preferences of molecules.
* Abstract published in Advance ACS Abstracts, March 15, 1994.
Employing a battery of these methods allows more complete informationabout the energy hypersurfaceof HD to be obtained. The conformation of HD can be described by four rotational angles ( ~ 1 - ( ~ 4 as , shown in Figure 1. The previous computational studies have unanimously identified the “all-anti” (a1= a2 = a3 = a4 = 180’) as the lowest energy ~onformation.4J”~~ This finding is consistent with expectation based on simple steric considerations and experimental results in the crystalline solid state for some related compounds such as 1,5-dibromopentane, 1,6-dichloro-and 1,6-dibromohexanes.l8 Interestingly, the AAAG conformer was identified as the lowest energy structure for 1,5dichloropentane,18a compound recently identified as a promising simulant for HD on the basis of electrostatic potential and molecular volume consideration^.^^ While no definitive experimental data exist for HD in the crystalline solid state, infrared and Raman studies at room conditions suggest the presence of multipleconformations.20 Additionally,a recent empiricalstudy predicts the AAAG, GAAG, GAAG’, and AAAA conformers of 1,5-dichloropentaneto be present in 39%, 27%, 27%, and 7%, respectively at 300 K in the gas phase.21 Clearly some conformational differences may be expected when a CH2 group is replaced with a sulfur atom in going from 1,5-dichloropentane to 2,2’-dichlorodiethyl sulfide, but there is reason to suspect that conformations other than the all-anti may be significantly populated in HD under room conditions. Our interest in HD conformations stems from efforts to accurately predict the vibrational infrared spectrum of HD. In a recent article,14 we made a comparison of the experimental vibrational infrared spectra of HD and some related hydrolysis products to those predicted by ab initio molecular orbital theory at the HF/6-311G** and MP2/6-31G* levels. Although the major lines in the experimentalspectrum could be matched with the calculated frequencies, there were some absorptions in the experimental spectrum that could not be successfully assigned. It is well-known that vibrational infrared spectra are sensitive to the conformational preferences of a molecule,22~23and this was suggested as a possible reason for thediscrepancies. In this paper, our objective is to identify other low-energy conformations of HD and determine if including them in a more thorough analysis might allow us to account for more lines in the experimental spectrum. Additionally, it is worthwhile to study the results
This article not subject to U.S. Copyright. Published 1994 by the American Chemical Society
Donovan and Famini
3670 The Journal of Physical Chemistry, Vol. 98,No. 14, I994 ReNIltS
\ H7
H8
6 1
H12
Figure 1. Torsional angles ( Y ~ - c Y and ~ atom numbering used for conformational study of sulfur mustard.
obtained from several different levels of theory to examine their relative strengths and weaknesses at predicting the geometries and relative energies of HD conformations. Establishing the preferred conformations of HD and the relative performance of some popular approximate methods allows a firm foundation to be set for future computational studies of the decontamination reactions involving HD.
Methods We studied HD conformations, making use of widely available procedures in molecular mechanics, semiempirical, and ab initio computer programs. In each case, full optimizations were computed with no symmetry constraints, so that all reported structures and conformations refer to the completely relaxed system. Our calculationswere implemented on a SiliconGraphics Iris 4D/210GTX, a Kubota Titan 3000, an IBM RS/6000 Model 560, or a Convex C3820 computer. We used the MacroModel 3.5a programz4 for all molecular mechanicscalculations,includingtheMM2*,MM3*,AMBER*, and OPLS* force fields (where the asterisk indicates programs to which authors made some minor modifications to the original force fields). We implemented all molecular mechanics calculations with the MacroModel default for treatment of electrostatic interactions, employing point charges and a distance-dependent dielectric. In order to identify the low-energy conformations of HD, we began with a MM2* Monte Carlo conformational search with minimization of 1000 structures using the all-anti conformation as input. The output from this computation, yielding 27 unique conformations, was then used for further study and refinement by other force field methods and by semiempirical andabinitiomethods. Thevalidityof thisapproach was confirmed by conducting additional Monte Carlo conformational searches with the MM3*, AMBER*, and OPLS* force fields. We applied the MOPAC 6.0 program2s.z for all semiempirical molecular orbital calculations. We transferred the 10 lowest energy HD conformations (and two additional higher energy structures) found by MM2* as input to the MOPAC program, using the MNDO, AM1, and PM3 Hamiltonians. To ensure the reliability of our results, we ran these optimizations with the PRECISE and GNORM=O.Ol keywords. For all MNDO and AM 1 calculations, the gradient norm was successfully reduced to less than 0.01 kcal/mol/& and for all PM3 calculations, the gradient norm was found to be less than 1.0 kcal/mol/A. We employed the Gaussian 92 program package for all ab initio molecular orbital calculations.27 Full optimizations were computed at the HF/3-21G, HF/6-311GS*, and the MP2/631G* levels, and singlepoint energies were evaluated at the MP2/ 6-31 1GS*//HF/6-311G** level. The frozen-core approximation22 was used for all MP2 calculations. Because the ab initio results were internally consistent for the 10low-energystructures identified by the force field study, we used the 3-21G method to optimize all 27 conformations and selected two additional conformers of relatively low energy for further analysis at higher levels of theory. Finally, vibrational frequencies were calculated at the HF/6-311G** level of theory on the four lowest energy HD conformations and compared to experimental data.
Table 1 lists the torsional angles (~1-4 of conformations 1-27 and their relative energies as determined by MM2* and HF/ 3-21G calculations. The rotamers selected for further study by other methods are identified by the “structure” heading. We selected the 10lowest energy conformations identified by MM2*, as well as two other rotamers found to be of relatively low energy by 3-21G. To determine if the MM2* calculations represented a sufficient sampling of the mustard hypersurface, we also ran separate Monte Carlo conformationalsearcheswith minimization using MM3*, AMBER*, and OPLS*. Although some additional conformations were located, these conformers optimized to previously located structures when they were optimized at the HF/3-21G level. Thus, it appears that all of the force field methods perform adequately in generating the initial set of structures for sulfur mustard, despite the apparent differences in torsional parameterizations(MacroModelreportsno “low quality” torsion parameters for an HD study using AMBER* or OPLS*, but two and six when MM2* and MM3*, respectively, are used). The local minima identified by MM2* and 3-21G agree well for most of the low-energy conformations, but there are differences for some of the higher energy conformations. For example, conformations 13, 17, and 18 all optimize to structure 11 at the 3-21G level, while existing as distinct local minima according to MM2*. A similar situation occurs for conformations 22 and 26 and again with conformations 23 and 24. Hence the number of unique local minima found by the HF/3-21G method is just 23. Table 2 compares the torsional angles (YI-LY~ for structures 1-12 located at the MM2*, AMI, and HF/6-311G** levels. These computational models were selected to illustrate the extent of variation in the torsional angles across the methods employed in this study. In general, the torsional angles predicted by the force field methods were internally consistent, as were the angles from the ab initio calculations, while the semiempirical methods were less consistent with each other. Table 2 shows generally close correspondence between the dihedral angles found by the MM2* and HF/6-311G** levels. Optimization at the semiempirical levels yielded geometries that agreed less well with those from MM2* and ab initio calculations for structures 1-12. For example, AM1 optimizes structure 5 to an a2 value of -92’, instead of the -178 and 169’ found at the MM2* and HF/63 11G**levels, respectively. Morestriking, thePM3 calculations make no distinction between structures 10 and 12 or between structures 7 and 11. For visual purposes, Figure 2 displays structures 1-12 as determined by the HF/6-3 11G**calculations oriented so that the ( ~ 1 - ( ~values 4 correspond to the data listed in Table 2. Table 3 summarizes the relative energies of structures 1-12 calculated by all the calculational techniques utilized in this study. The molecular mechanics methods are unanimous in predicting the all-anti structure 1 to be the most stable rotamer of HD. In contrast, the ab initio methods are unanimous in predicting structure 4, approximately AGGA, to be the most stable. There is little agreement about the lowest energy conformer among the semiempirical methods as MNDO, AM1, and PM3 identify 1, 4, and 8, respectively. Another interesting feature to examine is the range of energy differences between the high- and low-energy structures predicted by the calculations. The MNDO model seems to be the least discriminating among the techniques, as it finds all structures to be within 1.7 kcal/mol of each other. At the other extreme, the HF/3-21G calculations produce a range of 5.9 kcal/mol between the high- and low-energy structures. The molecular mechanics and high-level ab initio computations estimate this range between 4 and 5 kcal/mol. Table 4 presents a collection of the unscaled vibrational frequencies of the four lowest energy structures of HD, computed at the HF/6-311G** level, together with the corresponding
The Journal of Physical Chemistry, Vol. 98, No. 14, 1994 3671
Conformational Analysis of Sulfur Mustard
TABLE 1: Torsional Angles (degrees) and Relative Energies (kcal/mol) for Conformations 1-27 from MM2* and HF/I21C Calculations' conf
str
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
1 2
3 4 5 6 7 8 9 10
11
12
az 180 177 69 178 69 64 -69 177 71 69 -69 66 -7 1 62 63 70 -87 -8 3 71 -12 67 -7 1 66 61 71 -86 -62
180 179 67 179 69 69 -67 177 73 69 -69 70 -7 4 61 69 69 -74 -74 67 -7 5 67 -7 6 69 69 73 -76 -61
180 77 -179 81 -178 72 174 71 -105 -179 179 79 105 66 69 180 72 84 -104 103 109 105 79 60 -101 72 -66
a3
180 81 164 83 166 79 -162 82 -95 169 -1 66 81 95 57 19 164 95 95 116 85 162 91 80 80 -94 91 -58
180 176 180 81 80 175 76 -113 178 -179 -179 82 80 -109 171 77 62 67 179 -178 -12 17 79 60 -101 59 108
Ed
a4
180 175 176 83 81 179 84 -100 178 169 166 84 82 -101 -170 79 82 82 -89 150 -84 76 80 80 -94 16 104
180 180 180 178 178 180 177 180 180 69 69 179 179 180 -69 66 175 174 69 69 -177 66 66 61 71 62 68
180 180 179 179 180 180 180 -177 178 69 69 180 178 179 -69 70 178 178 74 66 180 68 69 69 73 68 72
0.00 0.66 1.27 1.38 1.85 1.86 2.07 2.22 2.30 2.58 2.69 2.77 2.94 2.95 3.27 3.28 3.32 3.41 3.58 3.61 3.69 4.18 4.25 4.28 4.32 4.33 4.66
1.94 1.01 3.86 0.00 2.83 3.62 3.09 0.94 2.34 5.90 6.44 2.74 1.38 3.14 5.89 6.22 1.38 1.38 3.44 3.98 3.09 3.55 5.85 5.85 2.04 3.55 6.42
a The conformations (conf) 1-27 are listed in order of increasing energy as calculated by the MM2* model. Structures (str) 1-12 were sclected for further study by other computational models. For all torsional angles ( a 1 4 and relative energies (&I), the first value listed in each column is from the MM2* model and the second value listed is from the HF/3-21G model.
experimentally measured values. The mode assignments were based on inspection of the nuclear displacements listed in the frequency calculation output. For several bands, particularly those at less than 1000 cm-l, more than one vibrational motion contributesto a given frequency. For simplicity,only the dominant vibrational motion is listed. We also matched the computed and experimental absorptions by inspection, placing greater emphasis on the frequencies but using the intensities to assist qualitatively. Our analysis only considers four structures because conformers more than about 2 kcal/mol above the ground state are not likely to be significantly populated under STP conditions. The HF/ 3-21G and MP2/6-3 1G* results suggest that structures 5 and 11 are equal to or lower in energy than 1, but at the HF/6-311G1* level these two structures are higher in energy than 1 and are omitted from our vibrational analysis. However, we did run frequency calculations on 5 and 11 to evaluate their zero-point vibrational energies (ZPVEs) .22 Discussion Conformational Geometry Predictions. When a variety of computational methods are applied on the basis of different calculational philosophies to a given system, some variation in the results may be expected. However, if all methods agree for a given property that they can determine, then the reliability of that result increases. When the results are not consistent, it becomes necessary to examine the relative strengths and weaknesses of the models to make predictions about the reliability of the computed results. With these thoughts in mind, we were pleasantly surprised to see the generally good agreement between the methods for geometry predictions. Since full optimizations were carried out for every model employed, we expected some structures that were identified as local minima by one model (such as MM2*) would turn out not to be local minima on the energy hypersurface of the other models. While this did occur in a few cases, particularly for PM3, there was good agreement between molecular mechanics and ab initio methods about the geometries of the local minima.
It is interesting that a previous ab initio study4 at the HF/ 6-3 1G level reports the energetics of an HD structure similar to 4 except that the a2 and a3 torsional angles were apparently constrained to 60°, rather than allowed to relax. The resulting structure was found to be 3.76 kcal/mol higher in energy than the all-anti structure. As Tables 1 and 2 indicate, by a2 and a3 being allowed relax to approximately 82O, this conformation becomes our global energy minimum for HD, lying approximately 2 kcal/mol below the all-anti structure. This example illustrates the importance of allowing full geometry optimizations when conformational searches are conducted: both geometries and relative energies can be significantly affected. Conformational Energy Predictions. The methods employed here increase the chances of locating the global energy minimum of HD because they allow for the consideration of conformations that may not be of obvious importance. For example, in a spectroscopic study of HD,Zo it was remarked that some HD conformations such as AGG'A should not be significantly populated because of expected steric hindrance. The AGG'A conformer approximately corresponds to structure 8 and, according to ab initio results, is even lower in energy than the allanti conformation, bearing in mind the deviation from the ideal gauche angle of 60'. The essential point here is that in molecules containing heteroatoms and freedom of several torsional angles, it is not always possible to predict the relative energies of given conformations from a simple steric considerations. Indeed, for the case studied here, molecular orbital theory appears to be needed to obtain a satisfactory ordering of the relative energies of the possible conformations. Clearly, the force field methods could be reparameterized to reproduce the ab initio results, but in their current state they do not yield reliable energetic data for sulfur mustard. This is not surprising in light of the lack of rigorously determined S-C-C-Cl torsional parameters presently incorporated in the force fields employed in our study. Turning next to the semiempirical methods, the AM1 model delivers the best performance compared to the ab initio values. Although AM1 seems to underestimate the energy differences
The Journal of Physical Chemistry, Vol. 98, No,14, 1004
3612
Donovan and Famini
TABLE 2: Comparison of Torsional Angles (degrees) from Geometry Optimized HD Structures 1-12 as Obtained from MM2*, AMI, and HF/6-311G8* Calculations structure MM2* AMI HF/6-311G** torsional angle 1
2 3 4
5 6 7 8 9 10 11 12 1
2 3 4 5 6 7 8 9 10
11 12
I 2
3 4 5
6 7 8 9 10
180 177 69 178 69 64 4 9 177 71 69 -7 I 71 180 77 -179 81 -178 72 174 71 -105 -179 105 -101 180 176 180 81 80 175 76 -113 178 -179
180 179 87 179 87 72 -88 176 82 87 -84 82 180
82 -I75 82 -92 78 172 92 -87 -175 88 -9 I I80 174 171 82 I04 -179 81 -92 -171 -175 81 -9 1
180 179 69 180 70 69 4 9 I77 73 70 -72 72 180 79 I71 83 169 77 -173 77 -88 173 98 -97
-156 173 82 -97 I80 179 I79 I80 I79 I80 I80 -178 -178 70 179 72
ai
a2
10
Figure 2. Conformations 1-12 of sulfur mustard as determined by the HF/6-311G** level of theory.
corrected the relative energies for vibrational contributions via ZPVEs.22 However, this correction is small, resulting in a destabilization of structure 4 relative to the other structures by 1 180 a, 2 I79 no more thanO.l kcal/mol. Taken together, aconsistent picture I78 3 emergies from the different levels of ab initio about the lowest 179 4 energy HD conformations: at least three structures are found to 174 5 be lower in energy than the all-anti structure 1, and structures -179 6 1, 5, 9, 11, and 12 are all close in energy. 7 I80 Vibrational Infrared Spectra Predictions. The literature 8 -176 9 I80 contains numerous examples illustrating the ability of ab initio 10 87 calculations to predict thevibrational infraredspcctra ofavariety I77 11 of compunds.'~'6~'2JO-1' The previous attempts at predicting 82 12 the vibrational infrared spectra of HD were performed at the HF/3-21G,15J6 HF/6-311G8*, and MP2/6-31Gw'4 levels of between the conformations somewhat, it does reasonably well at theory on just the all-anti conformation. Here we attempt to reproducing the order of the conformations. Thus, consistent improve the agreement between theory and experiment by withabinitio, AM1 predicts structure 4 tobe thelowest in energy, including additional low-energy conformers in the analysis. To and 10 to he the highest. These observations suggest that the make the analysis manageable, we have restricted our attention AMI model is the method of choice for efficiently delivering to structures within 1.5 kcal/mol of 4, according to the HF/6reliable results for HD. All of the semiempirical methods find 31 1G** calculations. Assuming the applicability of Boltzmann structures 4 and 8 to be of relatively low energy (in contrast to statistics, this approximation should allow for the inclusion of the molecular mechanics methods), but there is disagreement more than 90% of the HD conformers at 300 K. about structure 1. MNDO predicts 1to be the global minimum, The data in Table 4 indicate that the spectra predicted for whilePM3 findsit to benearly theleaststableofstructures1-12! structures 1,2,4, and 8 agree reasonably well with each other. Questions may be raised about the ability of the ab initio Most of the differences occur at lower frequencies, particularly calculations to deliver reliable relative energies, as previous for the C S stretch modes. The dependence of C-CI stretching conformational studies on glycine'8.29 have yielded results that frequencies on molecular conformations has been discussed,ls differ appreciably with basis set and correlation treatment. and it is plausible that C S stretching frequencies may demonAccordingly, we chose to examine the performance of small and stratea similarsensitivity. In termsofagreement with experiment, large basis sets (HF/3-21G and HF/6-311G**) and a simple adding more structures to the analysis should help the match level of electron correlation (MP2). Also, we determined the with experiment and indeed that is found here. In our recent MP2/6-3 11G**//HF/6-311G8* relativeenergies and found the s t ~ d y , '16 ~ of the 27 (59%) lines measured by experiment were results to he in line with the other ab initio methods, although successfully matched to the calculated lines for 1; in the present this method raised the relative energy of 1 by 1.1 kcal/mol work, wematch 24ofthe27 (89%) linesmeasured by experiment. comparedtotheresult fromtheHF/6-311G**//HF/6-311G** While this may appear to be a considerable improvement, most of the additional lines assigned were of relatively low intensity. level of theory. For structures 1, 2, 4, 5, 8, and 11, we have 11
12
80 -101 180 180 180 178 178 180 177 180 180 69 179 71
The Journal of Physical Chemistry, Vol. 98, No. 14, 1994 3673
Conformational Analysis of Sulfur Mustard
TABLE 3: Relative Energies (kcal/mol) of Sulfur Mustard Structures 1-12 (str)' str MM2* MM3* AMBER* OPLS* MNDO AM1 PM3 HF/3-21G HF/6-311G**b 1 2 3 4 5 6
7 8 9 10 11 12
0.00 0.66 1.27 1.38 1.85 1.86 2.07 2.22 2.30 2.58 2.94 4.32
0.00 0.38 1.02 0.82 1.36 1.28 1.48 1.96 2.23 2.07 2.62 4.17
0.00 0.54 1.58 1.21 2.08 2.30 2.26 2.27 2.28 3.20 3.01 5.17
0.00 0.64 0.68 1.41 1.29 0.89 1.55 2.56 1.02 1.47 1.49 2.02
0.00 0.33 0.88 0.60 1.10 1.39 1.31 0.33 0.74 1.74 1.03 1.16
1.34 0.67 2.39 0.00 0.87 2.08 1.75 0.21 1.27 3.42 0.62 1.12
3.13 1.97 1.51 0.84 1.53 3.46 1.28 0.00 2.34 1.72 1.28 1.72
1.94 1.01 3.86 0.00 2.83 3.62 3.09 0.94 2.34 5.90 1.38 2.04
1.41 0.72 2.80 0.00 2.06 2.76 2.30 0.86 2.35 4.28 1.77 2.98
MP2/6-31G*
MP2/6-311G**f
1.97 0.93 3.03 0.00 1.95 2.65 2.23 0.74 2.19 4.19 1.39 2.37
2.46 1.25 3.43 0.00 2.21 2.99 2.40 0.74 2.61 4.52 1.70 2.96
a All energies listed are relative to the lowest energy structure located for the model indicated. Lowest total energies for the MM2*, MM3*, AMBER*, and OPLS* force fields are 2.65,6.76, -6.83, and 6.29 kcal/mol, respectively. Lowest heats of formation for the MNDO, AMI, and PM3 methods are 45.24, -39.03, and -26.68 kcal/mol, respectively. Lowest total energies for the 3-21G, 6-31 1G**, MP2/6-31G*, and MP2/6-311G**/ /HF-6-311G** levels of theory are -1465.426 701, -1472.720 554, -1473.513 134, and -1473.730 544 hartrees, respectively. The (RHF ZPVE) energy differences, 4- X, for X = 1,2,5,8, and 11 are 1.35,0.70,2.02,0.83, and 1.74 kcal/mol, respectively. MP2/6-31 lG**//HF/6-311G** relative
+
energies.
TABLE 4 Comparison of the Calculated Unscaled Vibrational Frequencies of Structures 1,2, 4, and 8 to Experimental Data' str 2 str 4 str 8 exP mode str 1'4
C-Cl str C-Cl str CH2 bend C S str CH2 bend C S str CHI bend CH2 bend C-C str C-C str CH2 bend CH2 bend CH2 bend CH2 bend CHI bend CHI bend CH2 bend CH2 bend CH2 bend CHI bend CHI bend CHI bend CHI str CH2 str CH2 str CHz str CH2 str CH2 str CH2 str CH2 str
37.1 (0) 49.9 (0) 65.8 (1) 118.5 (14) 118.7 (0) 220.6 (8) 231.5 (0) 353.0 (1) 362.0 (4) 764.3 (34) 783.1 (131) 829.6 (0) 834.0 (4) 844.1 (8) 873.9 (4) 1065.7 (0) 1089.8 (0) 1107.8 (12) 1140.7 (2) 1243.0 (0) 1250.7 ( 5 ) 1352.8 (60) 1383.7 (48) 1408.4 (0) 1414.2 (2) 1467.6 (12) 1486.3 (4) 1611.8 (12) 1616.4 (2) 1616.5 (2) 1621.3 (0) 3214.7 (3) 3215.5 (25) 3256.8 (30) 3256.8 (3) 3267.6 (14) 3269.0 (0) 3321.2 (17) 3321.8 (0)
33.0 (0) 50.3 (1) 79.4 (3) 121.4 (4) 175.9 ( 5 ) 230.0 (9) 247.2 (1) 326.0 (4) 383.6 (0) 755.4 (41) 775.0 (126) 798.7 (4) 829.0 (3) 838.4 ( 5 ) 856.3 (12) 1066.3 (1) 1081.7 (1) 1118.1 (1) 1131.0 (7) 1244.0 (2) 1260.9 (4) 1366.6 (70) 1373.3 (29) 1413.4 (1) 1417.8 (1) 1469.6 (1 1) 1477.6 (8) 1593.8 ( 5 ) 1610.2 (4) 1615.7 ( 5 ) 1618.1 (0) 3217.3 (11) 3222.8 (10) 3256.7 (16) 3262.1 (13) 3271.4 (9) 3274.1 (3) 3321.7 (8) 3328.6 (9)
38.5 (1) 81.4 (3) 95.7 (1) 120.2 (4) 212.8 (0) 246.3 (17) 248.7 (2) 341.1 (2) 359.9 (0) 747.7 (52) 769.5 (131) 789.7 (0) 802.3 (11) 829.4 (7) 835.0 (2) 1041.1 (1) 1102.8 (1) 1118.2 (3) 1122.4 (2) 1246.7 (1) 1266.5 (12) 1357.2 (62) 1381.5 (15) 1412.1 (0) 1424.0 (0) 1468.2 (18) 1467.0 (13) 1589.8 (6) 1596.1 (0) 1611.2 (9) 1611.7 (1) 3226.4 (11) 3227.6 (3) 3261.8 (5) 3262.7 (32) 3276.2 (2) 3276.7 (2) 3327.7 (8) 3329.2 (9)
43.2 (1) 59.3 (0) 86.9 (3) 121.1 (4) 207.5 (1) 237.7 (13) 264.2 (3) 325.0 (2) 372.2 (0) 746.7 (47) 768.0 (139) 790.6 (1) 805.5 (10) 826.2 (7) 841.4 (2) 1045.8 (0) 1103.8 (1) 1119.2 (1) 1123.4 (3) 1241.9 (0) 1273.3 (11) 1361.6 (72) 1376.8 (15) 1414.7 (1) 1422.4 (1) 1463.7 (14) 1474.0 (11) 1591.7 (1) 1597.8 (10) 1610.0 (2) 1613.0 (3) 3222.8 (10) 3225.4 (6) 3259.2 (24) 3265.7 (16) 3272.6 (3) 3276.8 (3) 3325.3 (10) 3331.4 (9)
690 702 734 758 937 972 1021 1037 1134 1142 1208 1216 1268 1278 1295 1384 1406 1423 1443 2867 2915 2933 2964 3003
All frequenciesare listed in cm-' as computed by the 6-3 11G** model; the correspondingintensitiesare listed in parenthesis in km/mol. Frequencies from experimental data (exp) were matched on the basis of line position and intensity.
Previous studies14JS,30.31have found it convenient to determine correction factors from a comparison of the calculated and experimentally measured frequencies for each particular vibrational mode. Although a breakdown of correction factors by vibrational mode in this present study is not practical because of the limited number of data points involved, we can compute a single correction factor over all modes of 0.895 (with a standard deviation of the mean of 0.015 for the 2 4 frequencies). We obtained this factor by dividing the experimentally measured frequenciesz0by a weighted average of the computed frequencies
of structures 1,2,4, and 8 according to line intensity. Thus the standard scaling factor of 0.922 is appropriate for HD frequencies at the HF/6-311G** level of theory, resulting in a deviation from experiment of less than 2%. The fact that a match of structure 1 by itself produced reasonable agreement with the major lines from experiment suggests that an exhaustive approach as given here would only be necessary for demanding applications. For qualitative purposes, the spectrum from a single low-energy conformer at a suitable level of theory appears to be sufficient for a molecule such
Donovan and Famini
3614 The Journal of Physical Chemistry, Vol. 98, No. 14, 1994 as HD. As multiple frequency calculations on systems containing 198 basis functions are resourdemanding, the limited improvement in agreement between the calculated and experimental frequencies may not justify the additional computational effort. Of course, in systems containing many low-energy conformations, explicit consideration of many individual conformers may be required to obtain a satisfactory estimate of the experimental spectrum. In order to make such an assessment about a given system, a comprehensive conformational analysis is necessary.
Conclusions In summary, we have shown how molecular mechanics models favor structure 1 as the lowest energy conformer of HD while ab initio methods favor structure 4 and the semiempirical methods prefer 1,4,8fortheMNDO,AMl,andPM3models,respectively. While we have more confidence in the ab initio than either the molecular mechanics or semiempirical results, the molecular mechanicsmethods are of considerableutilityat making an initial, rapid screening of many different conformations, and the AM1 model holds promise for reactivity studies involving sulfur mustard. Although no approach can absolutely guarantee the location of a global energy minimum, for systems of size similar to HD, the chances of locating it are greatly improved by employing combined techniques such as used here. Hence this study has shown the utility of combining the best features of several computational methods rather than relying on just one method as is common practice. This eclecticapproachshould become increasinglyuseful as larger and more complex molecules become subject to computational investigations. Thus the minimum energy conformation of sulfur mustard in the gas phase can be represented by structure 4, lying approximately 0.75 kcal/mol lower in energy than the next lowest conformation, structure 8,and about 2.0 kcal/mol lower in energy than the all-anti structure 1. By conducting ab initio frequency calculations on the four lowest energy structures of HD at the HF/6-311G** level, we have obtained improved agreement with the experimentally measured spectra, but at considerable computational cost. For molecules with many low-energy conformations, it may be necessary to apply the type of analysis presented here to obtain satisfactory agreement with experiment. As a minimum, a conformational study of the molecule of interest is needed to determine the low-energy conformations and their relative energies. Now that we have establishedtheimportant low-energy structures of HD and achieved agreement between the calculated and experimentalvibrational infrared spectra, we are in a position to examine the rich reaction pathways open to this compound and will report the results of this work in due course.
Acknowledgment. W.H.D. acknowledges financial support of this work through the In-house Laboratory Independent Research (ILIR) program, US. Army ERDEC. We also thank Dr. Joseph J. Urban for helpful discussions and suggestions.
References and Notes (1) Papirmeister, B.; Feister, A. J. ;Robinson,S.I.; Ford, R. D. Medical Defense Against Musrard Gas, Toxic Mechanisms and Pharmacological Implications; CRC Press, Inc.: Boca Raton, FL, 1991. (2) Rink,S.M.;Solomon,M.S.;Taylor,M. J.;Rajur,S.B.;McLaughlin, L. W.; Hopkins, P. B. J. Am. Chem. Soc. 1993,115, 2551. (3) &vi%, L.; Elekes, I. Tetrahedron L.err. 1975, 29, 2477. (4) Broch, H.; Viani, R.; Vasileacu, D. Int. J. Quantum Chem. 1992,43, 511. (5) Yang, Y.-C.; Baker, J. A.; Ward, J. R. Chem. Rev. 1992,92, 1729. (6) Bartlett, P. D.; Swain, C. G. J. Am. Chem. Soc. 1949, 71, 1406. (7) Black,R.M.;Brewster,K.;Harrison,J.M.;Stansfield,N.Pharphorus, Sulfur Silicon Relat. Elem. 1992, 71, 3 1. (8) Hams, J. M.; Paley, M. S.;Sedaghat-Herati, M. R.; McManus, S. P. J. Org. Chem. 1985,50, 5230. (9) McManus, S. P.; Neamati-Mazraeh, N.; Hovanw, B. A.; Paley, M. S.; Harris, J. M. J. Am. Chem. Soc. 1985, 107, 3393. (10) Sedaghat-Herati, M. R.; McManus,S. P.; Harris, J. M. J. Org. Chem. 1988,53, 2539. (11) Yang, Y.-C.; Ward, J. R.; Luteran, T. J. Org. Chem. 1986, 51, 2156. (12) Yang, Y.-C.; Ward, J. R.;R. B. Wilmn,.J.; Burrows, W.; Winterle, J. S. Thermochim. Acta 1987, 114, 313. (13) Yang, Y.-C.; Szafraniec, L. L.; Beaudry, W. T.; Ward, J. R. J. Org. Chem. 1988,53, 3293. (14) Donovan, W. H.; Famini, G.R.; Jensen, J. 0.; Hameka, H. F. Phosphorous, Sulfur Silicon Relar. Elem. 1993,80, 47. (15) Hameka,H.F.;Emery,S.L.;Famini,G.R.;Leonard,J.M.;Reutter, D. J. Phosphorus, Sulfur SIIicon Relat. Elem. 1990, 53, 373. (16) Sasa, C.; Bartlett, R. J.; KuBulat, K.; Person, W. B. J. Phys. Chem. 1989, 93, 577. (17) De, A. U.; Ghose, A. K. Indian J. Chem. 1978, I6B, 1104. (18) Sakakibara, M.; Yonemura, Y.; Tanaka, Z.; Matsuura, H.; Murata, H.J . Mol. Srrucr. 1981, 70, 169. (19) Politzer, P.; Murray, J. S.;Concha, M. C.; Brinck, T. J. Mol.Srrucr. (Theochem) 1993,281, 107. (20) Christwen, S.D. J. Raman Spccrrosc. 1991, 22, 459. (21) Stalevik, R. J. Mol. Srrucr. 1993, 291, 59. (22) Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. Ab Initio Molecular Orbital Theory; Wiley-Interscience: New York, 1986. (23) Silverstein, R. M.; Bassler, G. C. Specrromerric Idenriflcarion of Organic Compounds; John Wiley Bt Sons,Inc.: New York, 1967. (24) Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Gaufield, C.; Chang, G.;Hendrickson, T.; Still, W. C. J. Compur. Chem. 1990,11,440. (25) Stewart, J. J. P. QCPE Bull. 1990, 10, 86. (26) Stewart, J. J. P. J. Comput.-Aided Mol. Des. 1990, 4, 1. (27) Gaussian92,RevisionB. Frisch, M. J.;Trucks,G. W.;Head-Gordon, M.; Gill, P. M. W.; Wong, M. W.; Foresman, J. B.; Johnson, B. G.; Schlegel, H.B.;Robb,M.A.;Replogle,E.S.;Gomperts,R.;Andres,J.L.;Raghavachari, K.; Binklcy, J. S.;Gonzalez, C.; Martin, R. L.; Fox, D. J.; Defrecs, D. J.; Baker, J.; Stewart, J. J. P.; Pople, J. A. Gaussian Inc., Pittsburgh, PA, 1992. (28) Frey, R. F.; Coffin, J.; Newton, S.Q.;Ramek, M.; Cheng, V.K. W.; Momany, F. A.; Schafer, L. J. Am. Chem. Soc. 1992, 114, 5369. (29) Hu, C.-H.; Shen, M.; Schaefer, H.F. J. Am. Chem. Soc. 1993,115, 2923. (30) Hameka, H. F. J. Mol. Srrucr. (Theochem) 1991,226, 241. (31) Hameka, H. F.; Carrieri, A. H.; Jensen, J. 0. Phosphorus, Sulfur Silicon Relat. Elem. 1992, 66, 1. (32) Durig, J. R.; Daeyaert, F. F. D. J. Mol. Srrucr. (Theochem) 1992, 261, 133. (33) Durig, J. R.; Wang, A.; Little, T. S.J . Mol. Srrucr. 1992, 269,285. (34) Durig, J. R.; Wang, A. J. Mol. Srrucr. 1993, 294, 13. (35) Hws,B. A.; Schaad, L. J.; Carsky, P.; Zahradnik, R. Chem. Rev. 1986, 86, 709. (36) Kwiatkowski, J. S.;Kubulat, K.; Person, W. B.; Bartlett, R. D.; Leszczynski, J. J. Mol. Srrucr. 1989, 198, 187. (37) Kwiatkowski, J. S.;Leszczynski, J. J. Mol.Srrucr. (Theochem) 1992, 258, 287. (38) Dempster, A. B.; Uslu, H. J. Mol. Srrucr. 1974, 21, 197.
