J. Phys. Chem. 1980,84,435-442
and this attack is primarily in the a system.
VII. Conclusions The MF-FSGO calculations suggest that the experimentally observed site specificity of the nucleophilic attack on the neutral species (viz. attack preferentially at C,) as well as the site specificity of the .rr-electrophilicattack on the anionic species (viz. attack preferentially at C,) are electronically controlled. The calculations also suggest that possible secondary sites of nucleophilic attack on the neutral species are C5and O2 and that O2 is both a possible secondary site for 7r-electrophilic attack and the primary site for a-electrophilic attack on the anions. References and Notes (1) This work was supported in part by the Department of Energy, the American Cancer Society, and the Petroleum Research Fund, administered by the American Chemical Society. (2) A participant in the Thesis Parts program administered by the Argonne Center for Educational Affairs. (3) R. Shapiro, R. E. Semis, and M. Welcher, J . Am. Chem. Soc., 92,
422 (1970). (4) D. V. Santi and C. F. Brewer, J. Am. Chem. Scc., 90,6236 (1968). (5) T. I. Kalman, Biochemistry, 10,2567 (1971). (6) R. L. Blakely in "Biochemistry of Folic Acid and Related Pteridines", Wiley, New York, 1969,Chapter 7. (7) M. Friedkin, Adv. Enzymol., 38,235 (1973). (8) P. V. Danenberg and C. Heuelberger, Biochemistry, 15,1331 (1976). (9) A. L. Pogobtti, K. M. Ivanetich, H. Sommer, and D. V. Santi, Biochem. Biophys. Res. Commun., 70, 972 (1976). (10) A. L. Pogolotti and D. V. Santi, Biochemistry, 13,456 (1974). (11) D. V. Santi and C. F. Brewer, Biochemistry, 12,2416 (1973). (12) D. V. Santi, C. S. McHenry, and H. Sommer, Biochemistry, 13,471 (1974). (13)C. A. Lewis, P. D. Ellis, and R. B. Dunlap, Biochem. Biophys. Res. Commun., 83, 1509 (1978). (14)C. A. Lewis, W. A. Munroe, and R. B. Dunlap, Biochemktry, 17,5362 (1978). (15) R. A. Byrd, W. H. Dawson, P. D. Ellis, and R. B. Dunhp, J. Am. Chem. Soc., 100,7478 (1978). (16) P. C. Plese and R. B. Dunlap, Biochem. Biophys. Res. Commun., 85,92 (1978). (17) J. Galivan, J. Noonan, and F. Maley, Arch. Biochem. Biophys., 184, 336 (1977). (18) P. C. Plese and R. B. Dunlap, J . Biol. Chem., 252,6139 (1977). (19) W. A. Munroe, C. A. Lewis, and R. B. Dunlap, Biochem. Blophys. Res. Commun., 80,355 (1978). (20) P. V. Danenberg, Biochim. Biophys. Acta, 473,73 (1977). (21) P. Reyes and C. Heidelberger, J . Mol. Pharrnacol., 1, 14 (1965). (22) D. V. Santi, A. L. Pogolotti, T. L. James, Y. Wataya, K. M. Ivanetich, and S. S. M. Lam, ACS Symp. Ser., 28, 57 (1976).
435
(23) R. J. Langenbach, P. V. Danenberg, and C. Heidelberger, Biochem. Bioohvs. Res. Commun.. 48. 1565 (1971). (24) P. V.Damnberg, R. J. Langenbach, and'C. Heidelberger, Biochsmisby, 13,926 (1974). (25) C. Heidelberaer, Ann. N . Y . Acad. Sci., 255,317 (1975). (26) F. J. Ansfieldand G. Ramirez, Cancer Chemother. Rep., 55,205 (1971). (27) L. Helson, M. Yagoda, M. McCarthy, M. L. Murphy, and I. H. Krakoff, Proc. Am. Assoc. Cancer Res., 11, 53 (1970). (28) I.H. Pitman, M. J. Cho, and G. S. Rork, J. Am. Chem. Soc., 96, 1840 (1974). (29) G. S.Rork and I.H. Pitman, J . Pharm. Sci., 64,216 (1975). (30) E. G. Sander and C. L. Deyrup, Arch. Biochem. Biophys., 150,600 (1972). (31) F. A. Sedor, D. G. Jacobson, and E.G. Sander, J . Am. Cbem. ~ O C . , 97,5572 (1975). (32) G. S. Rork and I. H. Pitman, J . Am. Chem. Soc., 97,5559 (1975). (33) R. E. Chrlstoffersen, Adv. Quantum Chem., 6, 333 (1972). (34) R. E. Christoffersen, D. Spangler, G. M. Maggiora, and G. 0. Hall, J . Am. Chem. SOC.,95,8526 (1973). (35) T. J. O'Donnell, P. R. LeBreton, and L. L. Shipman, J . Phys. Chem., 82,343 (1978). (36) S. Peng, J. Lin, M. Shabaz, and P. R. LeBreton, Int. J . Quantum Chem.: Quantum Biol. Symp., 5, 301 (1978). (37) K. Fukui, Fortschr. Chem. Forsch., 15, l(1970). (38) R. E. Christoffersen and L. E. Nitzsche in the "Proceedings of the International Conference on Computers in Chemical Research and Education", Ljubljano, Yugoslavia, July 1973. (39) Private communication from B. V. Cheney. The fluorine parameters were obtained by minhizatiin of the total energy of an HF molecular fragment with respect to FSGO centers and orbltal radii. The HF basis set consists of five FSGOs: one inner shell, one H-F bonding, and three F lone pair FSGOs. The inner-shell FSGO is placed on the H-F bond 0.000 68308 bohr radli from the F nucleus and Its c&kal radius is 0.21224304 bohr radii. The H-F bonding FSGO is also placed on the H-F bond 0.62281738 bohr radii from the F nucleus and its orbital radius is 1.171 87499 bohr radii. The three lone-pair FSGOs are arranged tetrahedrally with respect to each other and the H-F bond and are placed at distance of 0.364615 38 bohr radii from the F nucleus with orbital radii of 1.10625000 bohr radii. (40) L. L. Shipman and R. E. Christoffersen, Chem. Phys. Left., 15,469
(1972). (41) R. F. Stewart and L. H. Jensen, Acta Crystallogr., 23,1102 (1967). (42)L. Falion, Acta Crystallogr., Sect. 6 , 29, 1038 (1969). (43) "Tables of Interatomlc Distances in Molecules and Ions", The Chemical Society, Burlington House, London, 1965. (44)K. Ozekl, N. Skakabe, and J. Tanaka, Acta Crystallogr., Sect. 6 , 25, 1038 (1969). (45) P. D. Elk, R. B. Dunlap, A. L. Pollars, K. Siedman, and A. D. Cardin, J. Am. Chem. SOC.,95,4398(1973). (46) F. A. Sedor, D. G. Jacobson, and E. G. Sander, Biorg. Chem., 3, 221 (1974). (47) C. Yu and P. R. LeBreton, manuscript in preparation. (46) R. Shapiro, M. Welcher, V. Nelson, and V. Di Fate, B h h i m . Biophys. Acta, 425, 115 (1976).
Internal Rotation Potential Energy for the Glycine Molecule in Its Zwitterionic and Neutral Forms, A Comparison among Several Methods Paolo Palla, Carlo Petrongolo,' and Jacopo Tomasi Laboratorio di Chimica Quantistica ed Energetica Moiecolare del CNR, 56100 Pisa, Ita& (Received May 17, 1979) Publication costs assisted by Laboratorio di Chimica Quantistica ed Energetica Molecolare del CNR
Conformational maps for the internal rotations in glycine obtained with ab initio SCF calculations, CNDO, PCILO, extended Huckel, and classical methods are compared. The noticeable differences among the various results are analyzed and discussed. The parallel use of different methods for conformation studies seems to be advisable. Introduction Conformational studies largely rely upon approximate methods of determining potential energy surfaces. Several sets of empirical potential functions are today available for classical calculations, but no set can be recommended
as sufficiently reliable for general application, because they suffer of their empirical origin. In fact the parameters of a classical formulation of the conformational energy are selected on the basis of their ability to reproduce a limited amount of experimental data for a given specific class of
0022-3654/80/2084-0435$01.00/00 1980 American Chemical Society
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The Journal of Physical Chemistiy, Vol. 84, No. 4, 1980
Palla, Petrongolo, and Tomasi
TABLE I : Distances ( A ) and Angles for the Two Forms of Glycine zwitterzwitterC,-C’ C-0, C’-0, C,-N C,-H N-H 0,-H
ion
neutral
1.52 1.27 1.27 1.47 1.09 1.03
1.52 1.24 1.43 1.47 1.09 1.03 0.97
HNH HNC HCH NCH CC’O, O,C‘O, CO,H,
ion
neutral
109.47 109.47 109.47 109.47 119 122
109.47 109.47 109.47 109.47 120 120 120
\I
90;
chemical compounds. More general is the approach of the quantum-mechanical methods. The calculation of conformational energy maps is, however, for practical reasons generally performed only with semiempirical MO methods for which the question of the reliability arises again. For a check of reliability of the empirical or semiempirical results one is compelled to resort to more accurate calculations, i.e., to quantum-mechanical ab initio determinations of the conformational surface. Moreover, comparisons of this type should be performed for a large set of molecules representative of quite different classes of compounds, because only in this way will it be possible to evidence peculiar idiosyncrasies of one method or another for some specific arrangement of chemical groups. Ab initio conformational surfaces obtained by means of MOLCAO SCF wave functions of a single-l of double-!: accuracy (i.e., to a realistic accuracy level for such kinds of calculations for molecules of medium size) give indeed only approximate representations of the energy surface, and from a cautious point of view they could be considered nothing but another type of approximate surfaces, differing from the empirical and semiempirical ones in having different sources of error. The increasing number of ab initio molecular calculations seems to indicate-see, e.g., the reviews reported in the collective book “Applications of Electronic Structure Theory”,l-that even in the case of calculations with limited basis sets the conformational errors are in general quite limited. In addition, it must be stressed that the ab initio approach allows a gradual elimination of these approximations by improving, for example, the basis set. In spite of the increasing confidence in minimal basis SCF calculations, it is convenient to adopt the prudent position of considering, for every class of compounds brought under examination, these calculations nothing more than a first-order check, necessary as a starting point of a sequence of successive approximations to the correct answer. When extended calculations are not feasible, the approximation of the ab initio method can profitably supplement the corresponding pictures given by semiempirical or classical methods to get, by comparison of the different results, a more reliable description of the essential features of the surface. In this spirit we present here a comparison of the internal rotation potential surfaces for glycine in its neutral and zwitterionic forms, obtained using classical potential, the semiempirical CNDO and PCILO methods, and MOLCAO SCF ab initio calculations. The present results can be supplemented by those obtained by Caballol et ala2 using the extended Huckel semiempirical method (EH) and Scheraga’s classical potentials. Other conformational studies of glycine will be discussed too. Bond lengths and angles employed in this paper are reported in Table I; they have been obtained by a partial optimization by means of SCF calculations performed on the STO-3G basisa3 Some geometrical parameters slightly differ from those of ref 2, but we have checked that reasonable changes in bond lengths and angles did not sig-
0
30
\
60
i
120
90
P
S T O - 3G Figure 1. Internal rotation potential energy map for the zwitterion obtained from SCF LCAO MO calculations on the STO-3G basis. For symmetry reasons only a portion of the map is reported. The isoenergy curves are given in kcal/mol.
I
I
b : \ i 10
CNDO Figure 2. Internal rotation potential energy map for the zwitterion obtained from CNDO calculations.
nificantly alter the shape of the conformational maps. I n t e r n a l Rotation Energy Maps ( a ) The Zwitterion. The internal rotation potential of the zwitterion is defined according to the standard conventions by two rotation angles =
