6520
Molecular and Crystal Structure of 6-Methyluridine. A Pyrimidine Nucleoside in the Syn Conformation' D. Suck and W. Saenger* Contribution f r o m the Max-Planck-Institut f i r Experimentelle Medizin, Abteilung Chemie, Gottingen, Germany. Receioed February 28, 1972 Abstract: 6-Methyluridine crysta!lized from water in the monoclinic space group P21 with cell dimensions a = 19.895,b = 8.201, and c = 6.786 A, and /3 = 92.70", and two molecules per asymmetric unit. The crystal structure
has been determined from 2723 three-dimensional diffractometer measured data by direct methods and refined to a reliability index R = 4.9 %. 6-Methyluridine exhibits the syn conformation which seems to be stabilized mainly by the influence of the bulky methyl group in the 6 position of the base. The C(2')-endo pucker of the ribose units offers optimal steric conditions for this syn conformation nucleoside, which is obvious from the bond distances and angles showing no significant distortion compared to the corresponding values in nucleosides in the normal anti conformation. Due to the different orientation of the C(5')-0(5') bond in the two crystallographic independent molecules (gauche, gauche and trans, gauche, respectively)only one of the 6-methyluridine molecules shows an intramolecular hydrogen bond between O(5') of the sugar and O(2) of the bae. The 6-methyluracil bases are stacked along the c axis parallel to each other at interplanar spacings of 3.24 A.
N
ucleosides can assume two conformations, syn or anti,* depending upon the relative position of the base with respect to the sugar residue, i.e., depending upon the rotation about the glycosidic C(l ')-N(1) bond. Analysis of the rotational barriers and calculations of the energy profile of this rotation indicate that the anti conformation is favored slightly over the syn Conformation and that the pucker of the sugar ring influences the stability of the respective rotamer. 3--6 X-Ray structural investigations of several purine nucleosides indicate that, in the crystalline state, the syn conformation occurs almost as frequently as the anti conformation, but in the pyrimidine series only 4thiouridine, a naturally occurring t R N A nucleoside, has been found crystallized in the syn conformation.' It may be argued that in this special case the unusual packing and hydrogen bonding scheme and the previously unobserved C(3')-endo-C(4')-exo conformation of the sugar residue could contribute to the stabilization of the syn conformation. According to recent nmr studiess 6-methyluridine (Figure 1) exists in syn conformation even in aqueous solution. Therefore this nucleoside appeared suitable for a detailed X-ray structural study to obtain more insight into the correlation between the sugar conformation and the conformation about the glycosidic bond in pyrimidine nucleosides.
Experimental Section W e wish t o thank Dr. H . Vorbrhggen, Schering AG, who generously provided us with the thick, colorless. tabular 6-methyluridine crystals grown from an aqueous solution. The space group and cell constants of these crystals were determined from X-ray photographs and diffractometer measurements and are gathered in Table I. According t o the measured density of 1.54 g/cm3 there are two nucleoside molecules per assymmetric unit. (1) Preliminary publication: D. Suck, W. Saenger, and H. Vorbriiggen, Xaiure (London), 235, 333 (1972). (2) J. Donohue and K. N. Trueblood, J . Mol. Bicll., 2,363 (1960). (3) A . E. V. Haschemeyer and A. Rich, ibid., 27, 369 (1967). (4) A. V. Lakshminarayanan and V. Sasisekharan, Biochim. Biophys. Acta, 204, 49 (1970). ( 5 ) H. Berthod and B. Pullman, ibid., 232, 595 (1971). (6) S . Kang, J . Mol. Biol., 58, 297 (1971). (7) W. Saenger and K. H. Scheit. ibid.. 50, 153 (1970). (8) M. P. Schweizer, J . T. Witkowski, and R. K. Robins, J . Amer. Chem. Soc., 93, 277 (1971).
Table I. Crystallographic Data 19.895 + 0.003-A 8.201 i 0.002A c = 6.786 rt 0.002 A = 92.70 i 0.03" Monochromatized Mo radiation, X Space group P21 Molecules/cell Z = 4 Density pobrd = 1 ,540 g/cm3 P c n l o d = 1.543 g/cm2 Chemical formula C,CHUN,O~ a =
h
=
=
0,70926
Intensity data were collected from a crystal of dimensions 0.15 X 0.25 X 0.4 m m using a Stoe four circle automatic diffractometer equipped, with a Mo tube and a graphite monochromator ( A 0.70926 A). Altogether 2723 reflections (up t o a glancing angle 13 = 29") were measured in the Sj20 step scanning mode with a scan width of 80 steps (0.01" Sj0.02' 20 per step. 1 sec counting time); the backgrounds were measured by the stationary counterstationary crystal method for 20 sec on each side of a peak. The data were corrected for Lorentz and polarization factors but not for absorption due to the small linear absorption coefficient ( p = 1.4 cm-l).
Solution and Refinement of the Structure Normalized structure factors were computed from Eh = ( F h z / (F")' 2 with ( F * ) the observed magnitude of F2 averaged over a range of sin @A values appropriate t o Fh.g The structure was solved by direct methods using the program MULTAN'O which combines the cyclic application of the tangent formulag with multisolution techniques." The start phase set shown in Chart I, chosen automatically by the program, served to obtain the phases of the 199 Chart I
h 15 2 13 15 15 2 0 10 0
k 3 7 3 4 4 0
0 0 0
l 0 3 5
1 2 4 2
4 6
E 3.15 3.28 3.13 2.94 2.93 3.32 2.98 2.08 2.11
Phase, deg 45 45, 135, 225, 315 45. 135, 225, 315 0. 180 from Z1 relationships with probabilities >SO%
(9) J. Karle and H. Hauptman, Acta Crysrallogr., 9, 635 (1956). (10) P. Main, G. Germain, and M. M. Woolfson, M u L T A N (a system of computer programs for the automatic solution of noncentro-
symmetric crystal structures), YorkiLouvain, 1970. (11) G. Germain and M. M. Woolfson, Acra Crystallogr., Seci. B, 24, 91 (1968).
Journal of the American Chemical Society 1 94:18 / September 6 , 1972
6521 Table 11. Fractional Atomic Coordinates and Anisotropic Temperature Factors in the Form T = exp -(Pnh2 P22k2 P d 2 2 P d k 2Piahl 2P2~kl)"
+
Atom
H(2') H(C2') H(3') H(C3 ') H(4') H(5')
H(5') H(05')
+
+
+
X
Y
Z
-0.183411 -0.219211 -0.193611 -0.287811 -0.323911 -0.384911 -0.284012 -0.216211 -0.175012 -0.1093/1 -0.0796/1 -0,076611 -0.0093/1 0.035611 -0.021 311 0.024612 -0.070911 -0.0846/1 -0.31012 -0.30512 -0.14812 -0.13712 -0.20612 -0.09412 -0.10512 -0.11212 0.005/2 0.03512 0.014/2 0.02013 -0.03612 -0.10613
0.167013 0,020914 -0.112313 0.036714 0,180414 0.175514 0.325014 0.316214 0,470614 0,157614 0,046514 0.123113 0.0165/3 0.146013 0.017514 -0.147914 -0,255613 0.1003/3 -0.06317 0.42917 0.48211 0.47517 0.56717 0.26116 -0.054/6 0.104/7 -0.091/6 0.16617 0,07916 -0.19917 -0.13117 -0.18817
-0.21 3714 -0.226614 -0.238914 -0.219114 -0.212614 -0,195414 -0.227814 -0,224014 -0,231215 -0.192814 -0.029014 0,155813 -0.1049/4 -0.0550/? -0.328814 -0.427014 -0.338413 -0.3721/3 -0.20118 -0.21717 -0,10717 -0.33317 -0.25 117 -0.160/6 -0,02416 0.193/7 -0.05816 0,07617 -0.37417 -0.42417 -0.57817 -0,34018
Molecule A 0.0009jl 0.0060/3 0.0012/1 0.0065/4 0.001511 0.006313 0.001 111 0.008414 0.0012/1 0. 0105j5 0.001 110 0.015lj5 0.001 511 0.007414 0.0013/1 0.006314 0.0017/1 0.005214 0 .OOlOjl 0.006 114 0,001111 0.0063/4 0.0014/0 0.013214 0.001 111 0.0051/4 0.0012/0 0.008313 0.0012/1 0.0054/4 0.0019jl 0,007914 0.001811 0.0059/3 0.0014/0 0.008613 0.002 0.010 0.001 0.008 0.002 0.010 0.002 0.010 0.002 0.010 0.001 0.006 0.001 0.006 0.002 0.009 0.001 0.006 0.008 0,001 0.001 0.007 0.002 0.009 0.002 0.009 0.009 0.002
-0.303511 -0.342511 -0.4030/1 -0.307611 -0.238611 -0,214311 -0.2021/1 -0,233011 -0.193811 -0,337911 -0.394511 -0,366411 -0.435211 -0.4060/1 -0,428511 -0.486311 -0,476911 -0.365811 -0,33212 -0.15512 -0.201/3 -0.14913 -0,20513 -0,30412 -0,42512 -0.39612 -0.47812 -0,40612 -0.42512 -0.52712 -0.49012 -0.51913
-0.459813 -0.600914 -0.598613 -0.744913 -0,764014 -0.9021/3 -0.613914 -0,468414 -0.31 2714 -0.300413 -0.28 1414 -0.244013 -0,143914 0.012413 -0.1801/4 -0.2801/4 -0.308814 -0.2685/3 -0.836/7 -0,60817 -0.25617 -0.33018 -0.23317 -0.22316 -0.38217 -0.27917 -0.14417 0,02318 -0.08917 -0,21517 -0.38217 -0,32718
0,255313 0.2660/4 0.271214 0.267814 0,266114 0,262514 0,269914 0.262914 0.2621 15 0.246514 0.089214 -0,093613 0.177614 0.146613 0,399014 0,469714 0.675113 0.430413 0.25517 0,28417 0.13618 0.28618 0.38118 0,22216 0.07417 -0.17817 0.127/1 0.02018 0.41711 0,43717 0,39417 0.65718
Molecule B 0.001 111 0.007413 0.0012/1 0.007414 0.0013/1 0.008213 0 . 0015jl 0.006613 0.0014/ 1 0.009 114 0,001811 0.008914 0.001 111 0.010715 0.OOlOjl 0.0090/4 0,001111 0.0096/5 0,001111 0.006414 0.0012/1 0.007914 0.0017/1 0.0121/4 0,00121 1 0.0080/4 0.0024/1 0.008113 0,0011 / l 0.0079/4 0.001111 0.013415 0.00 151 1 0.0253/6 0,0011/ l 0.0016/5 0,001 0 . 0081 0.001 0. 0081 0.002 O.Oll/ 0.002 0.011 0.002 0.011 0.001 0.006 0.001 0.008 0.002 0.009 0.001 0.008 0.002 0.012 0,001 0.007 0.002 0.009 0,002 0.009 0.002 0.013
-
H(C2') H(3 '1 H(C3') W4') W5') H(5') H(05')
+
022
Pll
P33
612
P13
P23
0.014615 0.01 5617 0.0269/7 0.022417 0.0145/6 0.026616 0.012716 0.0098/6 0.0181/7 0.0126/5 0.01 1216 0.0123/4 0.0122/6 O.OlSOj5 0.012816 0.01 1816 0.016115 0.01 1414 0.015 0.012 0.014 0.014 0.014 0.009 0,009 0.014 0.009 0.012 0.010 0.013 0.013 0.013
-0.0001/ I
0.0003/ 1 0.0001/2 0.0002/1 -0.0001/2 -0.0003/2 -0. oooo/1 0.0003/2 0.0004/2 0.0005/2 0,0004/1 0.0005jl 0.0009/ 1 0.0005/ 1 0.0008/1 0,001211 0,001311 0.0001/2 0.0006jl 0.000 0.000 0.000
0.0003/4 0.0008/4 -0.0007/4 0,002615 0.003 115 0.007415 0.002014 0,001214 0.001714 -0.0003/4 0.0006/4 -0,002713 -0.0005/4 -0.0031/3 0.000914 -0,001 2/4 -0.0007/3 0.0020/3 0.000
0.013615 0.014416 0,029217 0.015816 0.01 1616 0.025417 0.012716 0.009915 0,025519 0.011315 0.011215 0.010614 0.0140/6 0.0181/5 0.012416 0.0145/6 0.013315 0.0114/5 0.012 0.012 0.016 0.016 0.016 0.009 0.011 0.013 0.012 0.017 0,011 0.013 0.013 0.018
-0.0006/1 -0,OOO4/ 1 -0.0008/1 0.0002/2 0.0004/1 0.0008/ 1 0.0001/1 -0.0002/ 1 -0.0005jl -0.0005/1 -O.OOOl/l 0 .oooo/ 1 -0.0006/1 -O.OOOl/l 0.0001/2 -0.0003/1 0.0006/ 1 0.000 0.000 0.000 0.000 0.000 0.000 0.000
0.000 0.000 0.000 0.000 0.000 0.000 0.000 -O.OOOl/l -0 .ooo2/1 -0.000211 -0.0003/ 1 0.0008/1 0.0008/1 0.0004/1 -0.000211 -O.OOO412 -0.0002/1 -0.0005/ 1 -0,001 511 -O.OOOl/l -0.0004/1 O.OOOl/l -0.0006/2 -0.001 312 0.0006/1 0.000 0.000 0.000 0.000 0.000 0.000 0.000
0.000 0.000 0.000 0.000 0.000 0.000 0.000
0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000
0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000
0.0007/1 0,001212 0.002111 0,001211 0.0007/2 0.0012j2 0.0004/ 1 0.0004/ 1 0.0000/2 0.0008/1 0.0005/ 1 0.0004/1 -0.0002/2 0.001I l l 0.0002/1 0.000412 0.0008/1 0.0004/1 0.000 0.000 0.000
-0.0000/4 0.001414 0.0021/4 0.0003/4 0.0007/4 -0.0001/4 -0.0007/4 -0.0019/4 -0.0009/5 -0.0005/4 -0.0001/4 0.0004/3 0,001114 0.0015/4 - 0,0018/4 -0.0003j5 0.002314 0.0009/4 0.000 0.000 0.000
0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000
0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0 IO00
~~~
a
Estimated standard deviations are separated by a slash.
E's greater than 1.7. The reflection 13 3 5 simultaneously served t o define the enantiomorph. Four out of the 64 phase sets resulting from the above combinations of starting sets showed approximately equally satisfactory figures of merit and R indices and were signifiCantlY more self-consistent that the other 60 phase sets. An attempt
was then made to determine the phases of the 245 E's of magnitude greater than 1.6 by application of the tangent formula, based on the starting phases of these best four phase sets with E > 1.7. However, as was only later discovered, the sequence of reflections of the first set was accidentally interchanged and the starting phase
Suck, Saenger 1 Molecular and Crystal Structure of 6-Methyluridine
6522 Table 111. Least-Squares Planes through the Bases and Ribose Units of Molecules A and Ba
O(4)
I
Atoms
op,
op1
H(031
H(027
N(l)+ C(2)+ N3)+ C(4)+ C(5)+ C(6)O(2) o(4) C(7) C(1‘) C(2’) H(3) W5) ~(71) ~(72) W73)
Figure 1. Chemical formula and numbering scheme of dmethyluridine. Chart I1
h 3
22 23 5 0
k 3 1 1 3 7
l 0 2 3 1
E 1.79 1.96 1.74 1.82
1
446
Starting phase, deg 360 315 180 315 180 45 45 360 180
C(l‘)+ (33‘)C(4‘)+ o(1’)C(2’) O(2’) O(3 ’) C(5’)
Phase angle after tangent refinement 318 331
_180 __
190 180 320 93 180 180
assignments (Chart 11) were in fact essentially “random.” Nevertheless, from an “ E map” based on the phases of the 245 E’s greater than 1.6 derived from the above random starting set, the positions of 20 atoms (the two pyrimidine rings plus substituents) could be correctly located. These 20 maxima were among the strongest maxima found in the map. From a subsequent Fourier synthesis phased with the information from these 20 atoms, the whole (nonhydrogen) structure could be deduced. The parameters of the 36 atoms were varied isotropically by least-squares full-matrix refinement * t o yield a disagreement lFcl//ZIFoI of l 0 . 3 z for the significant 2670 index R = ZliF,] reflections. The data were assigned weights based on counting statistics13 with 2W allowance for machine error and data with F, < 3aF0 were treated as unobserved and not included in the refinement process. Fifteen hydrogen atoms could be located in a difference Fourier synthesis at this stage, and the remaining hydrogen atoms, namely those of the methyl groups and of the 0 ( 2 ’ ) , 0(3’), and O(5’) hydroxyl groups, were found later. In the following four cycles of anisotropic refinement the hydrogen atoms were assigned the isotropic temperature factors of the atoms to which they were covalently bound. The positional parameters of the hydrogen atoms were refined in the last two cycles. The average parameter changes after the fourth least-squares refinement cycle were less than the estimated standard deviations. The final R factor is 4 . 9 z for the 2670 significant data and 5 . 4 z for all the 2723 measured data. Atomic scattering factors from the International Tables for X-Ray Cry~tallographyl~ were utilized throughout, and the function minimized was Zl/a2(1Fo~ -
-
Results and Discussion In Tables I-VI1 are gathered the crystallographic data, the final atomic parameters with standard deviations estimated from the least-squares variance-covariance matrix elements, the deviations of atoms from least-squares “best” planes through base and ribose (12) W. R. Busing, K. 0. Martin, and H. A. Levy, “A Fortran Crystallographic Report TM-305,” Oak Ridge, Tenn., 1962. (13) G. H. Stout and L.H. Jensen, “X-Ray Structure Determination,” MacMillan, New York, N. Y., 1968. (1 4) “International Tables for X-ray Crystallography,” Vol. 111, Kynoch Press, Birmingham, England, 1962.
o(59
A-
-Displacements, Molecule A
Molecule B
Basesb -0.055 0.047 0.003 -0.046 0.042 0,009 0.137 -0.156 0.042 -0,204 -1.312 -0.07 -0.04 -0.80 0.73 0.17
-0,030 0,024 0.003 -0.025 0.021 0.007 0.072 -0.080 0,022 -0.054 -1,107 -0.10 0.11 -0.82 0.17 0.85
Ribose Unitsc 0.012 -0.011 0.019 -0.020 -0.570 -0,122 1.323 -1.111 -2.397
0.018 -0,017 0.027 -0.029 0.571 0.133 - 1 ,385 1.275 1.250
+
+
+
The plane equations are of the form I X mY nZ p =0 where X, Y , and Z are along a , b, and c*, respectively. The plane defining atoms are marked by +. Molecule A , I = -0.0059, m = -0.0085, I r = -0.9999, p == -1.5149. Molecule B, / = -0.0097, m = 0.0224. / I = 0.9997, p = -1.7372. e Molecule A, 1 = 0.5140, m = 0.8548, FZ = - 0 . 0 7 1 8 , ~ = -0.1002. Molecule B, I = -0.5207. m -0.8458. ri = -0.1163, p = -5.4128.
Table IV. Endocyclic and Exocyclic Dihedral Angles within the Ribose Units C( 1’)-N( l)-C(6)-C(7) C(6)-N(l)-C(l ‘)-C(2’) C(6)-N(l)-C(l’)-O(l’) C(2)-N( I)-C( 1’)-C(2’) C(2)-N( 1)- C( 1’)-O( 1 ’) N(l)-C( 1‘)-C(2’)-0(2’) N(I)-C(l’)-C(2’)-C(3’) O( 1’)-C(l ’)-C(2’)-0(2’) 0 ( 1 ’)-C(l‘)-C(2’)-C(3’) C(l ’)-C(2’)-C(3‘)-C(4’) 0(2’)-C(2’)-C(3’)-0(3’) C( 1‘)-C(Z’)-C(3 ’)-0(3 ’) O(2 ’)-C(2 ‘)-C(3 ’)- C(4 ’) C(2’)- C(3 ’)-C(4’)-0( 1 ’) C(2’)-C(3’)-C(4’)- C(5 ’) O(3 ’)-C( 3 ’)-C(4’)-C( 5’) O(3 ’)-C( 3 ’)-C(4 ’)-O(1 ’) O(1’)-C(4’)-C(5’)-0(5’) C(3’)-C(4’)-C(5’)-0(5’) C(3’)-C(4’)-0(1 ’)-C(l’) C(5’)-C(4’)-0(1 ’)-C(1’) C(4 ’)-O( 1’)-C( 1‘)- C(2‘) C(4‘)-0(1 ‘)-C(1 ’)-N(1)
+5.2 +130.1 -109.1 -51.2 $69.6 -82.5 t158.6 1155.8 t36.9 -33.0 -37.0
f82.4 -152.4 $19.7 -101.2 +140.3 -98.7 -69.0 ;51.4 -3.6 +129.2 -25.8 -152.5
+o.o t131.3 -107.3 -51.9 +69.4 -81.9 t156.8 t155.7 1-34.3 -35.8 -37.8 +79.4 -153,l +26.4 -94.1 +147.4 -92.2 +61.9 -179.9 -5.2 +117.0
-18.6 -145.5
units, dihedral angles within the riboses, bond distances and angles involving hydrogen atoms, geometrical data of the hydrogen bonds, and short intermolecular distances, respectively. The observed and calculated structure factors are listed in the microfilm
Journal of the American Chemical Society / 94:18 / September 6 , 1972
6523
Figure 2. Stereoscopic view of the asymmetric unit. The atoms are represented by their 5 0 x probability thermal ellipsoids.
Table V. Bond Distances and Angles Involving Hydrogen Atoms” Atoms H(3)-N(3) W5)- C(5) H(71)-C(7) H(72)-C(7) H(73)-C(7) H( 1 ’)-C( 1’) H(2 ’)-C(2’) H(02’)- O(2’) H( 3’)- C( 3 ’) H(03’)-O(3 ’) H(4 ’)-C(4 ’) H( 5 ’l)-C( 5’) H(5’2)-C(5’) H(05’)-0(5’)
Molecule A
Table VI. Geometric Data of the Hydrogen Bonds and Short Nonbonded Interactions Molecule B Donor
Bond Distances, A 0.93 0.95 0.98 1.05 1 .oo 0.92 0.97 0.78 0.97 0.90 0.93 0.98 1.05 0.88
Bond Angles, Deg H( 3)-N( 3)-C( 2) 113 H(3)-N( 3)-C(4) 120 H(5)- C(5)- C(4) 119 H(5)-C( 5)-C(6) 119 H(~I)-C(~)-C(~) 109 H(72)-C(7)-C(6) 117 H(73)-C(7)-C(6) 110 H(71)-C(7)-H(72) 101 HUI)-C(~)-H(~~) 110 H(72)-C(7)-H(73) 110 H(1’)-C(1 ’)-N(1) 107 H ( 1 ’)-C( 1 ‘)-O(1 ’) 113 H ( l ’)-C(l’)-C(2’) 105 H(2’)-C(2’)- C( 1 ’) 110 H(2‘)-C(2’)-0(2’) 110 H(2’)-C(3’)-C(3’) 111 102 H ( 0 2 ’)-O(2’)-C( 2 ’) H(3’)-C(3’)-C(2’) 107 H(3’)-C(3‘)-0(3’) 115 H( 3 ‘)-C( 3’)-C(4’) 111 109 H(03’)-0(3’)-C(3 ’) 104 H(4 ‘)-C(4 ’)-C(3 ‘) H(4’)-C(4’)-0(1’) 110 H(4‘)-C(4 ‘)-C(5’) 111 H(5 ‘l)-C(5’)-C(4‘) 111 H(5’2)-C(5 ’)-C(4’) 111 109 H(5 ‘1)-C(5’)-0(5 ’) H(5’2)-C(5’)-0(5’) 111 H(5 ’1)-C(5’)-H(5 ’2) 102 H(05’)-0(5 ’)-C(5 ’) 97
0.90 0.94 0.98 0.90 1.08 0.95 1.03 0.85 0.91 0.85 0.92 0.98 0.98 0.86 116 116 124 114 110 112 113 110 110 102 105 110 109 114 110 108 103 111 109 114 105 114 106 107 105 110 112 112 108 80
The averaged estimated standard deviations are 0.05 for distances and angles, respectively.
edition of this journal. l5
Figures 2-5
N(3M O(2‘)A O( 3 ’)A O(5‘)A N3)B O(2’)B O(3 ’)B O(5‘)B O(5’)B C(Z‘)A C(2‘)B
A
Acceptor (A) O(2‘)B 0 ( 4 ~ O(5’)A O(3’)B O(5‘)B 0(4)a
O(3‘)B 0(2)b 0(2)a 0(2)B
Distances D . ;.A, A 2.930 2.870 2.849 2.81.7 2.881 2.692 2.731 3.048 2.979 2.924 2.888
Distances Angle H . ;.A. H-A-D, A deg 2.04 2.11 1.99 2.01 2.03 1.87 1.99 2.39 2.56 2.29 2.26
14 9 16 20 15 12 26 35 53 41 44
012') Figure 3. Bond angles and distances in molecules A and B. (Data for molecule B in parentheses.) The average estimated standard deviations are 0.005 A and 0.3”, respectively. and 2‘
illustrate a
(15) A table of structure factors will appear following these pages in the microfilm edition of this volume of the journal. Single copies may
stereoscopic view of the asymmetric crystallographic unit, bond distances and angles, and projections of the be obtained from the Business Operations Office, Books and Journals Division, American Chemical Society, 1155 Sixteenth St., N. W., Washington, D. C. 20036, by referring to code number JACS-72-6520. Remit check or money order for $3.00 for photocopy or $2.00 for microfiche.
Suck, Saenger 1 Molecular and Crystal Structure of 6-Methyluridine
6524
i Figure 5. Projection of the crystal structure along the c* axis. Oxygen and nitrogen atoms are marked by heavy lines and dots, respectively. Bonds in molecules A are filled and hydrogen bonds are indicated by dotted lines.
L
C %
Figure 4. Projection of the crystal structure along the b axis (rotated by 10” about the a axis). Hydrogen bonds are indicated by dotted lines,
crystal structure along the b axis and the c* axis, respectively. Conformation of 6-Methyluridine. Ribose Units. Both ribose units exhibit a C(2’)-endoo puckering conformation with atom C(2’) being 0.57 A from the leastsquares mean plane through the other four atoms of the ribose ring and on the same side as atom C(5’) (Table 111). This ribose conformation is also indicated by the values of the five endocyclic ribose torsion angles and evident from the small dihedral angles C(3’)-C(4’)-0(1’)-C(l’), -3.6” in molecule A and -5.2” in molecule B, respectively (Table IV). The most prominent difference between the two crystallographically independent 6-methyluridine molecules of the asymmetric unit is found in the orientation of the C(5’)-0(5’) bond with respect t o ribose moieties. In molecule A the conformation about the C(4’)-C(5’) bond is gauche,g a u ~ h e ’ ~ (, ~~ ’O O= -69.0”, ~ O C= 51.4”) with O(5’) located “above” the ribose and in intramolecular hydrogen bonding contact with the base oxygen atom 0(2), Table VI. In molecule B however, this conformation is gauche,trans ( ~ O O = 61.9”, q o C = -179.9’) and O(5’) cannot participate in an intramolecular hydrogen bonding interaction with the heterocycle O(2) (16) M. Sundaralingam, J. Amer. Chem. Soc., 87, 1067 (1965). (17) E. Shefter and K. N. Trueblood, Acta Crystallogr., 18, 1067 ( 1965).
Journal of the American Chemical Society
94:18
atom. The latter conformation seems to be preferred in 6-methyluridine since it was also found from nmr spectroscopic investigation that the conformation about the C(4’)-C(5’) bond in 6-methyluridine in aqueous solution is not gauche,gauche but trans,gauche or gauche,trans. l8 Conformation about the Glycosidic Bond. The torsion angles C(2’EC( 1’)-N( lEC(6) which define the conformation about the glycosidic C( 1’)-N( 1) bond7 are 130.1” in molecule A and 131.3’ in molecule B. Thus, both 6-methyluridine molecules are in syn conformation. Since 6-methyluridine is in the syn conformation even in solution8 whereas 4-thiouridine assumes the anti conformation as soon as the crystals dissolve,8,19,20 one could infer that 6-methyluridine is in the syn conformation due t o the bulky methyl group. But then in 6-methyluridine the 0(5’)-H. . . O(2) intramolecular hydrogen bond should be of only minor importance for the stabilization of the syn conformation as is indicated in its crystal structure. Only one of the two molecules in the asymmetric unit shows this intramolecular hydrogen bond. Bond Distances and Angles. 6-Methyluracil Units. Bond angles and distances within the 6-methyluracil residues of molecules A and B are showing no significant differences and are in reasonable agreement with averaged data for other uracil derivatives. The heterocycles are in the usual diketo form with double bonds between atoms C(2)-0(2), C(4)-0(4), and C(5)-C(6) In Table I11 are collected the deviations of some atoms from the best planes through the pyrimidine rings. The deviation from planarity is greater for molecule A than for molecule B. The atqm C(1’) deviates from the mean b+se plane by 0.204 A in molecule A but by only 0.054 A in molecule B; in both molecules the deviation is toward the same side of the base plane as atom C(2’).
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(18) F. E. Hruska, “The Jerusalem Symposium on Quantum Chemistry and Biochemistry, Jerusalem, 1972,” Vol. V, E. D. Bergmann and B. Pullman, E,d., Academic Press, New York, N. Y., in press. (19) I
