J. Phys. Chem. 1992, 96, 9198-9200
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14N NQR and ab Inltio MO Calculations of Quinolines, Naphthyrldhres, and Benzodiazhres Juan Murgic4* Yosslen Amy? Hmberto J. Soscun,+ Centro de Qdmica, fWC, Apartado 21827, Caracas 1020A. Venezuela
and Robert A. Marino Department of Physics and Astronomy, Hunter College of CUNY, New York,New York 10021 (Received: February 7, 1992)
The 14N NQR spectra of quinoline, 2-chloroquinoline, 1,s-naphthyridine and its hydrated form, 1,I-naphthyridine, 1,3benzodiazine, 2,3-benzodiazine, 1,2-benzodiazine, and 1.4-benzodiazine were obtained at 77 K. Also the N electric field gradient EFG for quinolines, naphthyridines, and benzodiazines was calculated using an ab initio method with a 6-31G* set. The effect of an additional ring and the substitution of a neighboring C by a N atom on the N EFG was interpreted by means of the topology of the charge distribution of the corresponding monocyclic azines used as model compounds.
Iaboduction The polycyclic azines are an important part of many compounds of great pharmaceutical interest.' In particular, quinoline and similar azines are found in antimalarials such as chloroquine, primaquine, pamaquine, etc.' Several benzodiazines and naphthyridines have also been found to have a wide bacteriostatic activity.' The action of these molecules has been linked to their electronic distribution* so a 14NNQR study was undertaken at 77 K. In this work, two quinolines, several naphthyridines, and benzodiazines were studied as a first step in understanding its charge distribution. An ab initio calculation of the electric field gradient EFG using a 6-31G' basis set was also undertaken for some quinolines, naphthyridines, and benzodiazines as a further help in understanding their electronic distribution. A reasonable agreement between the calculated and the experimental nuclear quadrupole coupling constant was obtained for the polycyclic azines. The calculated asymmetry parameter of the field gradient, as usual in this type of calculation, showed larger difference with the experimentalvalues than the coupling constants. The reasons behind this discrepancy are also discussed. The changes observed in the EFG as a result of the addition of a benzene ring and by the substitution of a neighboring C by a N atom are analyzed in terms of the variations of the topology of the charge distribution of the N valence shell in model monocyclic azines.
Experimental and Computational Details The I4N NQR spectra were obtained with a MATEC-NICOLET pulsed FT ~pectrometer.~ The samples were obtained from commercial sources and were purified using standard methods. Several of the liquid azines at room temperature formed glasses on cooling so the samples were induced to form small seed crystals at the bottom of the vial by submerging the container in liquid N2 for a few seconds. After the seeds were formed, the vials were held at 2-3 mm above the N2surface for several hours to achieve full crystallization. In this way, relatively sharp NQR lines were obtained in most cases except in quinoline, where only broad lines were observed. The molecular geometries were first optimized with the MONSTERGAUSS 86 program4using a STO-3G set. The ab initio MO and EFG calculations, using these geometries, were performed in an IBM 3090 computer using the KGNMOL program5with a 6-31G' basis set and standard exponents and factors: The topological properties of p(r) and its Laplacian were calculated with a locally modified version of the AIMPAC package.'
Results As I4N has a spin I = 1, usually two NQR lines are observed per each crystallographically inquivalnt N site.* The lines are 'On leave from the Departamento de Quimica, Fac. Exp. de Ciencias, Universidad del Zulia, Maracaibo, Venezuela.
Y* = (3e2qQ/4h)(l f 7/3), where e2qQ/h is the nuclear quadrupole coupling constant (Q = nuclear quadrupole moment) and 7 is the asymmetry parameter of the EFG. The components of the gradient are such that q1k = aZV/ax,dxk,where xi and xk = x , y , and z and Vis the electrostatic potential produced by the charges located outside the nucleus, 7 = lqxx - qyyl/lqzzland eq = qzzin the NQCC. In general, the spectra of the bicyclic azines were similar to those of the corresponding monocyclic azines* showing the close relationship that exists between their charge distribution. As seen in Table I, quinoline showed four lines indicating the existence of two inequivalent sites per unit cell. The line widths in quinoline were around 10 kHz, suggesting the presence of some molecular disorder. 2-Chloroquinoline only showed two NQR lines indicating the existence of only one inequivalent N site in the crystal. In anhydrous 1,5-naphthyridine, a pair of lines was detected while four were found in the hydrated sample. Two of the lines of the last sample were at the same frequencies of pure 1,5-naphthyridine, while the other pair showed a noticeable frequency shift. The above results show that the sample was actually a mixture of both hydrated and anhydrous 1,s-naphthyridine. For most of the benzodiazines, two inequivalent N sites were found at 77 K (see Table I). In 1,3-benzodiazine,four N sites were observed,showing the existence of two molecules in the asymmetric unit of the crystal. In Table I are shown the observed and the calculated NQCCs and asymmetry parameters for the N atoms of several unsubstituted bicyclic azines. Additionally, in Table I1 are shown the calculated values of the NQCC of isoquinoline and other unsubstituted naphthyridines and benzodiazines. A good linear correlation was found between the experimental and calculated values of the NQCC of the benzodiazines with r = 0.945. The values of the NQCCs were within 3% for the azines except in 2,3-benzodiazine where it was around 6%.
Discussion As usual, the calculated 7 values showed a much larger discrepancy than the coupling constants! This discrepancy has been found even in the comparison of values derived from gas-phase microwave data and from complex CI calculation^.^ There are several s o u m for this variance in the azines: one is the sensitivity of r] to the molecular charge distribution p ( r ) , another is linked to the crystal contribution to the EFG, and the third one is related to the thermal averaging of the gradient in the solid. In 7, the three diagonal components of the EFG are involved in its definition. Each of them is a very small difference between two large numbers: the electronic and the nuclear contribution. Then, a change of only a few percent in any of these large numbers will have dramatic effects on 7. This problem is particularly severe when qxxis close to qvy,because a minute fractional shift in one
0022-3654/92/2096-9 198$03.00/0 @ 1992 American Chemical Society
The Journal of Physical Chemistry, Vol. 96, No. 23, 1992 9199
14NNQR Spectra of Quinolines
TABLE I: Calculated and Observed NQR Parameters in Bicyclic Azine@ 2Qq(kHz)
compound
v+ ( W Z )
ouinoline
2-chlorcquinoline 1,S-NAPY 1,S-NAPYH 1.8-NAPY 1,3-BDIAZ
2,3-BDIAZ 1,2-BDIAZ 1,4-BDIAZ
v-
(Wz)
3769 3723 3440.4 3728.7 3712.5 3706.5 3667.8 3727.3 3640.0 3578.5 3573.0 3890.8 3867.8 3769.1 3740.0
3020 2974 3079.6 2976.2 2996.4 2964.5 2927.5 2931.1 2902.2 2882.9 2870.1 378 1 .O 3660.9 3637.0 3609.0
3790
2938
obsd
7
calcd
obsd
Calcd
4495
4458
0.333
0.418
4347 4470 4476 4422
4355 4520
0.250 0.367
4470
0.167 0.337 0.320 0.335
0.332
4351
N ( l ) 4280
0.337
N( 1) 0.223 N(3) 0.175
N(3) 4077 5100
4776
0.043
0.148
4918
N ( l ) 4828
0.053
N( 1) 0.371
4486
N(2) 4893 4615
0.380
N(2) 0.362 0.591
"NAPY = naphthyridine; NAPYH = naphthyridine monohydrate; BDIAZ = benzodiazine. The values of the NQCC and 7 obtained by NQR correspond to the averaged value for all the inquivalent sites of the unit cell of the crystal. No calculation were made for NAPYH.
-
TABLE II: Calculated NOCC in Bicvclic AN atom compound" NQCC (kHz) N(1) 4586 ISOOUIN Nilj 4384 1&GAF'"H N(2) 4591 2,6-NAPTH N(2) 4501 2,7-NAF'TH 4526 1,7-NAPTH N(1) 4737 N(7) a ISOQUIN
7
0.418 0.344 0.475 0.369 0.423 0.415
is isoquinoline and NAPH is naphthyridine.
of them will automatically generate a large variation in q. As Seen from the definition of q, variations in qrrwill also contribute to its changes but in a lesser degree than the other two components. Then, unless each of the qr,sis calculated to an extremely high and very expensive degree of accuracy, q will have much larger uncertainties than the NQCC that only contains qrr. This requirement seems to be the main reason because in most papers dealing with EFG calculations only the NQCC is reported. Another source of discrepancybetween calculated and measured values of q arises from the fact that the NQR spectra are obtained in the solid state where the crystal field contributes to the EFG.8 As the gradient is calculated in an isolated molecule in the present case, the crystal contribution is not taken into account with the consequent uncertainties in q. In the solid state, the lattice vibrations produce an averaging of the field gradientE that was not considered in the present calculation where a static molecule was employed. The large size of the molecules makes the calculation of the EFG with a more extended basis set and the CI method, in a vibrating cluster of molecules, prohibitively expensive in terms of computer time. Then, one has to use the present values until the advance in hardware turns such calculation feasible. Generally, the interpretations of the EFG have been made in terms of the populations of localized atomic orbitals centered at the quadrupolar nucieus (Townes and Dailey's theoryE). Nevertheless, the orbitals and their populations are not physical o b servables as defined by quantum mechania,l0 so the information about the charge distribution obtained by means of this interpretation is open to serious questions. An alternative way of obtaining information about the molecular charge distribution is to interpret the EFG directly in terms of an observable such as p(r). Nevertheless, from p(r) one can not determine directly the regions where the electronic shells are located.1° This is a significant shortcoming because the most (or one of the most) important contribution to the EFG arises from the shells of the atom containing the quadrupolar nucleus.ll An efficient method of locating the regions of space where p ( r ) is locally concentrated or depleted involves the uselo of the Laplacian V2p(r).The study of the distribution of V2p(r)shows that the valence shell in a free
atom is a sphere on whose surface p(r) is a local maximum.'O The charge distribution on this sphere is uniform in atoms without a nucleus with a large quadrupole moment. For light atoms with very low Q values such as N, the resulting distortion of the shells can, in most cases, be neglected.8 The formation of covalent bonds produces a number of small local extremes in the valence shell that are a function of the number, spatial distribution, and nature of the intervening atoms.1° The EFG reflects the asymmetry in p ( r ) around the nucleus so a connection between the extremes in the V2p(r)of the N valence shell and the gradient present at its nucleus was found recently in cyanides and nitriles," imines and diimides,12 and monocyclic azines.13 In order to obtain reliable information about the topology of p(r), it is necessary to use wavefunctions of highest quality.1° As mentioned before, this approach is not possible due to the size of the molecules studied in this work. Nevertheless, ab initio MO calculations using triple tbasii sets with polarization in monocyclic azines are viable with present day computers. For this reason, pyridine and the other monocyclic azines were chosen as model molecules and the topology of their charge distribution was ob tained.12J3 The resulting topology of p(r) of the N(l) valence shell distributionshowed a nonbonding maximum Mnbin the "lone pair" position and one of the bonded type Mb in each of the C-N( 1) (or N-N(1)) bond directi~ns.'~J~ A correlation of the value of V2p(r)at h f n b and Mb with the components of the EFG tensor for the two-coordinated N atoms has shown that the N NQCC is determined by the valued2J3of V2p(r)at kinkIn other wards, the NQCC in azines reflects mainly the N "local" charge environment. The similarity between the NQCC of the bicyclic and the corresponding monocyclic azine8 shows that the addition of the benzene ring does not change significantly the N coupling constant from the value found in the monocyclic azines. Then, with the results obtained above, the addition of an extra benzene ring does not seem to perturb s u b stantially the Mnbmaximum that is responsible for the N NQCC. The topology of p(r) in compounds having two-coordinated N atomsl2" showed that q not only contains contributions from the valence shell of the N atom but also includes contributions from the rest of the molecule. The "nonlocal" contribution explains the reasons of the higher sensitivity of q to the addition of a benzene ring (seeTable I). This effect suggests that the inclusion of this type of substituent should be more noticeable in q than in the NQCC. Therefore, q is a better tool than the NQCC if one is exploring substituent effects in the azines. The ab initio calculation made in the different monocyclic azines12J3showed that the value of the V2p(r)at Mb on the N(l) valence shell is decreased by the substitution of a neighboring C by a N atom. The charge rearrangement produced by the other N atom results in a redistribution of the entire valence shell8
J. Phys. Chem. 1992, 96, 9200-9204
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(backpolarization) of the N( 1) atom in order to balance the forces that act on its n ~ c l e u s . ' ~ItJ ~has been found that a decrease in the value of V2p(r) at Mb results in an increase in ~ a l u e ' ~atJ ~ Mnb (the N "lone pair"). Then, the observed increase in the NQCC of N(1) when the neighboring C is substituted by a N atom is the result of the backpolarization of the N( 1) valence ~ h e l l ' ~that J ~ increases Mnb. Acknowledgment. We want to thank the CONICIT of Venezuela for partial support and to the Centro Cientifico of IBM de Venezuela C.A. for a generous grant of computer time.
References and Notes (1) Goodman, L. S.;Gilman, A. The Pharmacological Basis of Therapeurics, 5th ed; McMillan: New York, 1975. (2) Singer, J. A.; Purccll, W. P. J. Med. Chem. 1%7,10,754. Stembach, L. H. Drug Res. 1978,22,229. Hahn, F. E.; OBrien, R. L.; Ciak, J.; Allison, J. L.; Olenick, J. G. Mil. Med. 1966, Suppl, 1071.
(3) Murgich, J.; Abanero, J. A.; Santana, R. M.; Capparelli, M. V. J . Chem. Phys. 1986,85, 6047. (4) Monstergauss 86, Bonnacorsi, R. Istituto di Chimica Quantistica ed Energetica Molecolare del C.N.R., Pisa. Italy. ( 5 ) KGNMOL, from the MOTECC package, IBM Corporation Center for Scientific and Engineering Computations, Kingston, NY 12401. (6) Ditchfield, R.; Hehre, W. J.; Pople, J. A. Chem. Phys. 1970,54724, (7) Biegler-Kilnig, F. W.; Bader, R. F. W.; Nguyen-Dang, T. T. J. Comp. Chem. 1982, 3, 317. (8) Lucken, E. A. C. Nuclear Quadrupole Coupling Comranrs;Academic: New York, 1969. Smith, J. A. S.Chem. Soc. Reo. 1986, 15, 225. (9) Palmer, M. H. Z . Narurforsch. 1985,41a, 147. Cremer D.; Kriiger, M. J. Phys. Chem. 1992, 96,3239. (IO) Bader, R. F. W. Atoms in Molecules: a Quantum Theory; Oxford University Press: Oxford, 1990. (11) Aray, Y.; Murgich, J. J . Chem. Phys. 1989, 91, 293. (12) Aray, Y.; Murgich, J. X International Symposium on NQR Spectroscopy, Kings College, London, 1991; J . Chem. Phys., in press. (13) Aray, Y.; Soscun, H.; Murgich, J. Inr. J. Quantum Chem. 1991,25, 587. (14) Amy, Y.;Murgich, J. J . Am. Chem. SOC.1991, 113, 7135.
Ab Initio Cluster Calculations of the Electron Density and Electric Fleld Gradient In Corundum Anthony S.Brown and Mark A. Spackman* Department of Chemistry, University of New England, Armidale NSW 2351, Australia (Received: March 26, 1992; In Final Form: August 7 , 1992)
Ab initio calculations have been performed using mixed basis sets on two clusters carefully designed to model bulk corundum. Computational results on the clusters are compared with crystal Hartree-Fock results and with experiment for the deformation electron density and for the electric field gradient at the oxygen nucleus. Inclusion of polarization functions on central oxygen atoms in the clusters results in quantitative agreement with electron distributions derived from X-ray diffraction data. Although none of the ab initio cluster results for the oxygen electric fEld gradient tensor agree well with the experimental NMR values, agreement improves with increased basis set flexibility and better design of the cluster.
introduction The electrostatic properties of corundum, particularly the electron density distribution and the electric field gradient (EFG) tensors at the nucIar sites, have been the subject of recent interest, much of it arising from speculation about the "ionic" or "covalent" character of the bonding. Corundum is often describtd as having an essentially ionic structure, but a number of experimental'.2 and theor~tical'~ studies indicate that there is significant covalent character in the A 1 4 bonds. A clear understanding of the electron density and EFG tensors in corundum has not emerged from these studies, however, and anomalies are evident in both the experimental and theoretical electron density distributions. Previous theoretical approaches include work by Nagel: who performed multiplescattering Xa (MSXa) calculations using an A1209cluster in which the aluminum atoms are in 6-fold coordination as in the crystal but none of the oxygen atoms are in the appropriate &fold coordination with aluminum. As much of the intmst in the electron density distribution of corundum is focused on the region near the oxygen atoms,' in this respect the AI2O9 cluster is deficient. Nagel also performed calculations on A140 and AIOd clusters, with cluster geometries as in the crystal, in order to determine the EFG tensors at the aluminum and oxygen nuclear positions. Good agreement with experiment was obtained for aluminum, but very poor agreement was obtained for oxygen; the inadequacy of the clusters and the use of a muffin-tin potential were cited by Nagel as possible reasons for the poor result. Crystal Hartree-Fock calculations on corundum have been reported by Dovesi and co-~orkers.~'Such calculations, which account for the periodicity of the solid, offer advantages over cluster calculations, but current applications are limited to highquality calculationson simple crystal types or to calculations
of moderate quality on more complex structures, i.e., those with large unit cells or low symmetry. In this context, corundum is a large system having 10 atoms in the primitive unit cell and relatively low symmetry. Crystal Hartree-Fock deformation electron densities for corundum have been reported using a m i n i i l STO-3G basis set43and most recently with an extended basis set: The recent work used a modified 6-21G basis set, but it was found by Salasco et al. that in order to increase the basis set flexibility even further by the addition of polarization functions, it was necessary to perform the calculations with "poor" computational 0onditions.S However, even with the poor computation conditions in that work, it was only possible to add polarization functions to either the aluminum atoms or the oxygen atoms but not to both simultaneously. To allow the best possible description of corundum, it would be highly desirable to use the most flexible basis set possible on both the aluminum and oxygen atoms. The electron distribution in corundum has been the subject of several experimental studies. Lewis et al.' have provided the most detailed results to date from multipole refinements performed on two different singlecrystal X-ray diffraction data sets. Some of that data were also reanalyzed by Kirfel and Eichom* as part of a study of the utility of synchrotron radiation in electron density studies. Unfortunately, there were substantial discrepancies between the electron deformation densities and EFG tensors resulting from the synchrotron and conventional X-ray data sets in the latter study. In a separate study, we have carefully reanalyzed all diffraction data for corundum and explored the use of powder diffraction data to provide an alternative to model-dependent corrections to extinction-affected reflection^.^ An important outcome of that study was a resolution of these discrepancies, and in conjunction with the present work, it confirmed the correctness
0022-3654/92/2096-9200303.00/00 1992 American Chemical Society
