Synthetic peptide helices in crystals: structure and antiparallel and skewed packing motifs for alpha-helices in two isomeric decapeptides

The isomeric decapeptides Boc-Aib-Ala-Leu-Ala-Aib-Aib-Leu-Ala-Leu-Aib-OMe (II) and Boc-Aib-Ala-Aib-Ala-Leu-Ala-Leu-Aib-Leu-Aib-OMe (III), are predominantly alpha-helical with little effect on the conformation with interchange of Aib/Ala residues or Aib/Leu residues. The packing motif of helices in crystal II is antiparallel, whereas the helices pack in a skewed fashion in crystal III, with a 40 degrees angle between neighboring helix axes. Crystal III contains a water molecule in a hydrophobic hole that forms hydrogen bonds with two carbonyl oxygens that also participate in 5----1 type hydrogen bonds. Values for helical torsional angles phi and psi assume a much wider range than anticipated. Crystal II: C49H88N10O13, space group P2(1), with a = 16.625 (2) A, b = 9.811 (5) A, c = 18.412 (3) A, beta = 99.79 (1) degrees, Z = 2, R = 5.7% for 4338 data with magnitude of F0' greater than 3 sigma(F). Crystal III: C49H88N10O13 x 1/2H2O, space group P2(1) with a = 11.072 (2) A, b = 34.663 (5) A, c = 16.446 (3) A, beta = 107.85 (1) degrees, Z = 4, R = 8.3% for 6087 data with [F0[ greater than 3 sigma(F).     

Dinuclear macrocyclic polyamine zinc(II) complexes: syntheses, characterization and their interaction with plasmid DNA

The syntheses, characteristics of dinuclear macrocyclic polyamine zinc complexes and their interaction with plasmid DNA are reported. The two cyclen (1,4,7,10-tetraazacyclododecane) moieties are bridged by rigid and flexible linkages. The crystal structures of Zn2C27H43N8O15Cl4 [5c.(ClO4)3.2H2O] and Zn2C30H43N10O13Cl3 [5e.(ClO4)3.H2O] have been determined. The complexes crystallize in the monoclinic space group C2/c and P2(1)/c with the following unit cell parameters: 5c.(ClO4)3.2H2O: a=32.568(4)A, b=14.8593(17)A, c=19.443(2)A, alpha=90.00 degrees , beta=119.435(4) degrees , gamma=90.00 degrees , Dc=1.551 mg/m3, FW=956.71, F(000)=3932; 5e.(ClO4)3.H2O: a=15.807(2)A, b=16.756(2)A, c=16.161(2)A, alpha=90.00 degrees , beta=97.062(4) degrees , gamma=90.00 degrees , Dc=1.546 mg/m3, FW=988.83, F(000)=2032. The distance between the two Zn(II) ions is about 4.0 A. The structures show that two zinc ions can synergistically interact with the substrate DNA. With this novel structural characteristics, the dinuclear macrocyclic polyamine Zn(II) complexes via the synergetic effect between the two zinc ions can catalyze the cleavage of plasmid DNA (pUC18) with unprecedented speed at physiological conditions.     

Apolar peptide models for conformational heterogeneity, hydration, and packing of polypeptide helices: crystal structure of hepta- and octapeptides containing alpha-aminoisobutyric acid

The crystal structures of two helical peptides Boc-Val-Ala-Leu-Aib-Val-ala-Leu-OMe (VALU-7) and Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe (VALU-8) have been determined to a resolution of 1.0 and 0.9 A, respectively. Both the seven and eight residue peptides crystallize with two conformers per asymmetric unit. The VALU-8 conformers are completely helical and differ only at the C-terminus by a sign reversal of the phi, psi angles of the last residue. One of the VALU-7 conformers occurs as a normal alpha-helix, whereas in the other, the N(7)--O(3) alpha-type hydrogen bond is ruptured by the entry of a water molecule (W) into the helix, which in turn makes hydrogen bonds N(7)...W = 2.97 A and W...O(3) = 2.77 A. The other side of the water molecule is surrounded by a hydrophobic pocket. These two conformers give a static representation of a step in a possible helix unwinding or folding process. In the VALU-8 crystal the helices aggregate in a parallel mode, whereas the aggregation is anti-parallel in the VALU-7 crystal. The crystal parameters are VALU-7, P2(1), a = 10.203 (3) A, b = 19.744 (6) A, c = 22.561 (6) A, beta = 96.76 degrees, Z = 4, C38H69N7O10.0.5H2O, R = 6.65% for 3674 reflections observed greater than 3 sigma (F); and VALU-8, P2(1), a = 10.593 (4) A, b = 27.57 (6) A, c = 17.745 (5) A, beta = 95.76 (3) degrees, Z = 4, C42H76N8O11.0.25 CH3OH, R = 6.63% for 4701 reflections observed greater than 3 sigma (F).     

Parallel and antiparallel aggregation of alpha-helices. Crystal structures of two apolar decapeptides X-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe (X = Boc, Ac)

An apolar helical decapeptide with different end groups, Boc- or Ac-, crystallizes in a completely parallel fashion for the Boc-analog and in an antiparallel fashion for the Ac-analog. In both crystals, the packing motif consists of rows of parallel molecules. In the Boc-crystals, adjacent rows assemble with the helix axes pointed in the same direction. In the Ac-crystals, adjacent rows assemble with the helix axes pointed in opposite directions. The conformations of the molecules in both crystals are quite similar, predominantly alpha-helical, except for the tryptophanyl side chain where chi 1 congruent to 60 degrees in the Boc- analog and congruent to 180 degrees in the Ac-analog. As a result, there is one lateral hydrogen bond between helices, N(1 epsilon)...O(7), in the Ac-analog. The structures do not provide a ready rationalization of packing preference in terms of side-chain interactions and do not support a major role for helix dipole interactions in determining helix orientation in crystals. The crystal parameters are as follow. Boc-analog: C60H97N11O13.C3H7OH, space group Pl with a = 10.250(3) A, b = 12.451(4) A, c = 15.077(6) A, alpha = 96.55(3) degrees, beta = 92.31(3) degrees, gamma = 106.37(3) degrees, Z = 1, R = 5.5% for 5581 data ([F] greater than 3.0 sigma(F)), resolution 0.89 A. Ac-analog: C57H91N11O12, space group P2(1) with a = 9.965(1) A, b = 19.707(3) A, c = 16.648(3) A, beta = 94.08(1), Z = 2, R = 7.2% for 2530 data ([F] greater than 3.0 sigma(F)), resolution 1.00 A.     

Synthesis, structure and spectroscopic properties of two models for the active site of the oxygenated state of cytochrome P450 [corrected

Two dioxygen adducts of thiolato-iron(II) porphyrins, [K(222)][Fe(TPpivP)(SC6HF4)(O2)] 1a and [Na(18c.6)][Fe(TPpivP)(SC6HF4)(O2)] 2 were synthesized by reaction of O2 with five-coordinate, high-spin, cryptated alkali metal thiolato-iron(II) 'picket fence' porphyrinate. They were characterized by visible and infrared spectroscopy: lambda max (log epsilon) = 360 nm (4), 427 nm (4.69), 560 nm (3.69), 610 nm (3.40) for both compounds; v(16O-16O) = 1139 cm-1 in chlorobenzene and fluorobenzene for 1a and 2. Single crystals of composition [K(222)][Fe(TPpivP)(SC6HF4)(O2)].[K(222)](SC6HF4)(C 6H5Cl)(H2O) 1b were obtained by diffusion of pentane/xylene mixtures into chlorobenzene solutions of 1a at -5 degrees C. Single crystals of composition [Na(18c.6)][Fe(TPpivP)(SC6HF4)(O2)] were obtained by slow diffusion of pentane into benzene solutions of 2. Structures of 1b and 2 were studied at 20 degrees C (1b) and -100 degrees C (1b and 2). 1b: space group P2(1)/c (monoclinic), a = 16.806(5) A (1.6806 nm), b = 14.331(4) A (1.4331 nm), c = 52.000(15) A (5.2000 nm), beta = 92.95(2) degrees, V = 12.507 A3 (12.507 nm3), Z = 4, Dcal = 1.28 g.cm-3 (t = 20 degrees C). The final R1 factor was 0.085 for 5238 reflections having I greater than 3 sigma(I). 2: space group P2(1)/c (monoclinic), a = 13.107(3) A (1.3107 nm), b = 27.055(4) A (2.7055 nm), c = 25.029(4) A (2.5029 nm), beta = 96.84(2) degrees, V = 8812 A3 (8.812 nm3), Z = 4, Dcal = 1.18 g.cm-3 (t = -100 degrees C). The final R1 factor was 0.088 for 6587 reflections having I greater than 3 sigma(I). The iron atom is, in both compounds, bonded to the four porphyrinato nitrogens (Np), the sulfur atom of the axial thiolate and one oxygen atom of the axially end-on bonded dioxygen molecule. The average Fe-Np distance found in 1b [1.994(4) A, 0.1994 nm] is not significantly different from that found in 2 [1.993(3) A, 0.1993 nm]. The Fe-S bond length is 2.367(3) A (0.2367 nm) in 1b and 2.365(2) A (0.2365 nm) in 2. The Fe-O1 distances with the oxygen atom of O2 bonded to iron are respectively 1.837(9) A (0.1837 nm) and 1.850(4) A (0.1850 nm). The end-on bonded O2 molecule is disordered in both complexes 1b and 2.(ABSTRACT TRUNCATED AT 400 WORDS)     

Synthesis and crystal structures of Boc-L-Asn-L-Pro-OBzl.CH3OH and dehydration side product, Boc-beta-cyano-L-alanine-L-Pro-OBzl

Boc-L-Asn-L-Pro-OBzl: C21H29O6N3.CH3OH, Mr = 419.48 + CH3 OH, monoclinic, P2(1), a = 10.049(1), b = 10.399(2), c = 11.702(1) A, beta = 92.50(1)degrees, V = 1221.7(3) A3, dx = 1.14 g.cm-3, Z = 2, CuK alpha (lambda = 1.54178 A), F(000) = 484 (with solvent), 23 degrees, unique reflections (I greater than 3 sigma(I)) = 1745, R = 0.043, Rw = 0.062, S = 1.66. Boc-beta-cyano-L-alanine-L-Pro-OBzl: C21H27O5N3, Mr = 401.46, orthorhombic, P2(1)2(1)2(1), a = 15.741(3), b = 21.060(3), c = 6.496(3) A, V = 2153(1) A3, dx = 1.24 g.cm-3, Z = 4, CuK alpha (lambda = 1.54178 A), F(000) = 856, 23 degrees, unique reflections (I greater than 3 sigma(I)) = 1573, R = 0.055, Rw = 0.078, S = 1.86. The tert.-butyloxycarbonyl (Boc) protected dipeptide benzyl ester (OBzl), Boc-L-Asn-L-Pro-OBzl, prepared from a mixed anhydride reaction using isobutylchloroformate, Boc-L-asparagine, and HCl.L-proline-OBzl, crystallized with one methanol per asymmetric unit in an extended conformation with the Asn-Pro peptide bond trans. Intermolecular hydrogen bonding occurs between the methanol and the Asn side chain and between the peptide backbone and the Asn side chain. A minor impurity due to the dehydration of the Asn side chain to a beta-CNala crystallized with a similar extended conformation and a single intermolecular hydrogen bond.     

Helix-forming tendencies of amino acids depend on the restrictions of side-chain rotamer conformations: crystal structure of the tripeptide GAI in two crystalline forms.

In our attempts to design crystalline alpha-helical peptides, we synthesized and crystallized GAI (C11H21N3O4) in two crystal forms, GAI1 and GAI2. Form 1 (GAI1) Gly-L-Ala-L-Ile (C11H21N3O4.3H2O) crystals are monoclinic, space group P2(1) with a = 8.171(2), b = 6.072(4), c = 16.443(4) A, beta = 101.24(2) degrees, V = 800 A3, Dc = 1.300 g cm-3 and Z = 2, R = 0.081 for 482 reflections. Form 2 (GAI2) Gly-L-Ala-L-Ile (C11H21N3O4.1/2H2O) is triclinic, space group P1 with a = 5.830(1), b = 8.832(2), c = 15.008(2) A, alpha = 102.88(1), beta = 101.16(2), gamma = 70.72(2) degrees, V = 705 A3, Z = 2, Dc = 1.264 g cm-3, R = 0.04 for 2582 reflections. GAI1 is isomorphous with GAV and forms a helix, whereas GAI2 does not. In GAI1, the tripeptide molecule is held in a near helical conformation by a water molecule that bridges the NH3+ and COO- groups, and acts as the fourth residue needed to complete the turn by forming two hydrogen bonds. Two other water molecules form intermolecular hydrogen bonds in stabilizing the helical structure so that the end result is a column of molecules that looks like an incipient alpha-helix. GAI2 imitates a cyclic peptide and traps a water molecule. The conformation angles chi 11 and chi 12 for the side chain are (-63.7 degrees, 171.1 degrees) for the helical GAI1, and (-65.1 degrees, 58.6 degrees) and (-65.0 degrees, 58.9 degrees) for the two independent nonhelical molecules in GAI2; in GAI1, both the C gamma atoms point away from the helix, whereas in GAI2 the C gamma atom with the g+ conformation points inward to the helix and causes sterical interaction with atoms in the adjacent peptide plane. From these results, it is clear that the helix-forming tendencies of amino acids correlate with the restrictions of side-chain rotamer conformations. Both the peptide units in GAI1 are trans and show significant deviation from planarity [omega 1 = -168(1) degrees; omega 2 = -171(1) degrees] whereas both the peptide units in both the molecules A and B in GAI2 do not show significant deviation from planarity [omega 1 = 179.3(3) degrees; omega 2 = -179.3(3) degrees for molecule A and omega 1 = 179.5(3) degrees; omega 2 = -179.4(3) degrees for molecule B], indicating that the peptide planes in these incipient alpha-helical peptides are considerably bent.     

Thiourea derivatives and their nickel(II) and platinum(II) complexes: antifungal activity

We have synthesized two thiourea derivatives of methyl anthranilate (1, 2) and their complexes with nickel (3) and platinum(II) (4). We have also prepared the complexes of nickel(II) with two benzoylthiourea derivatives (5, 6). The obtained compounds were characterized by elemental analysis, spectroscopic methods (FT-IR, UV-vis, NMR), mass spectrometry and thermal analysis. Compound 1, C(20)H(23)N(3)O(2)S, crystallizes in monoclinic space group P21/n, with Z=4, and unit cell parameters, a=8.8042(4) A, b=7.6608(3) A, c=28.834(2) A, alpha=gamma=90 degrees, beta=90.94(1) degrees. Compound 2, C(20)H(21)N(3)O(3)S, crystallizes in monoclinic space group P21/c, with Z=4, and unit cell parameters, a=7.7345(4) A, b=8.6715(4) A, c=29.113(2) A, alpha=gamma=90 degrees, beta=90.67(1) degrees. Compound 5, C(24)H(30)N(4)NiO(2)S(2), crystallizes in monoclinic space group P21/n, with Z=4, and unit cell parameters, a=10.4317(8) A, b=18.517(2) A, c=13.299(1) A, alpha=gamma=90 degrees, beta=104.53(1) degrees. Compound 6, C(25)H(28)Cl(2)N(4)NiO(4)S(2), crystallizes with a molecule of CH(2)Cl(2) in triclinic space group P-1, with Z=2, and unit cell parameters, a=10.362(1) A, b=11.849(2) A, c=12.536(2) A, alpha=90.04(2) degrees, beta=84.73(1) degrees, gamma=113.43(2) degrees. Compounds 1 and 2 show antifungal activity against the major pathogens responsible for important plant diseases (Botrytis cinerea, Colletotrichum fragariae, Fusarium oxysporum and Phoma betae). The antifungal activity is practically the same for morpholine and ethyl derivatives.     

Variability in the backbone conformation of cyclic pentapeptides. Crystal structure of cyclic(Gly-L-Pro-D-Phe-Gly-L-Ala)

All the peptide bonds in cyclic(Gly-L-Pro-D-Phe-Gly-L-Ala) are in the trans conformation; however, the peptide bond C'5-N1 is twisted by 19 degrees from planarity (omega 5 = -161 degrees). A Type II beta-turn encompasses the L-Pro-D-Phe residues. Carbonyl oxygens O2, O4 and O5 are directed to the same side of the average plane through the backbone ring and they form hydrogen bonds with N3, N5 and N1, respectively, in adjacent molecules in a stacked column where the adjacent molecules are related by one translational unit. The conformation of the backbone is different from that established in other molecules with the DLDDL chirality sequence. The P21 cell contains two molecules of C21H26N5O5 with a = 4.836(2) A, b = 18.346(8) A, c = 12.464(5) A and beta = 100.05(4) degrees. The R factor for 1382 data with [F0[ greater than 1 sigma is 7.0%.     

The X-ray structure and absolute configuration of the anticancer drug (+)-4-ketocyclophosphamide

4-Ketocyclophosphamide (4-keto CP), C7H12Cl2N2O3P, monoclinic, P2(1), a = 11.909 (2), b = 10.254 (1), c = 9.873 (1) A, beta = 91.08 (1) degrees, V = 1205.45 (3) A3 Z = 4, Dc = 1.51 Mg-m-3, Cu K alpha, lambda = 1.54178 A, alpha 25 = +53.8 degrees (c = 3.0, MeOH), m.p. 107 degrees C, mu = 61.8 cm-1, F (000) = 564, R = 0.064 for 2961 observed reflexions with I greater than 1.96 sigma(I). Dextrarotatory enantiomer of 4-keto CP has S configuration at the stereogenic center. One of the two crystallographically independent molecules is disordered both in a six-membered ring and in --N(CH2CH2Cl)2 moiety. With the exception of a less populated conformer of a disordered molecule, 4-keto CP molecules adopt a conformation in which 1,3,2-oxazophosphorinane ring is in the sofa form with C(6) deviating from the plane through the remaining five ring atoms while an exocyclic N atom with its three substituents is nearly coplanar with the phosphoryl oxygen atom O(8). In a less populated conformer, the six membered ring takes the form of sofa with C(5) as a flap while an exocyclic N atom and its substituents are oriented toward the P--N(3) bond.     

Ring conformation of cyclic octapeptide cyclo (L-Pro-Sar)4 in the crystalline state

A single-crystal X-ray diffraction analysis has been made of the structure of the cyclic octapeptide cyclo(L-Pro-Sar)4. The material [C32H48O8N8 X (21/4) H2O X (1/2) CH3OH, Mr = 799.43] crystallizes in the monoclinic space group C2 with cell dimensions a = 14.544 (3), b = 11.902 (2), c = 14.064 (3), and beta = 122.26 (2) degrees (lambda = 1.54178 A, T = 293 K). The final R value for the 1980 observed reflections is 0.079. The ring conformation has the peptide bond sequences of cis-cis-trans-trans-cis-cis-trans-trans (Pro-Sar-Pro peptide bond linkages are cis-cis- or trans-trans). The pyrrolidine rings in the four proline residues take an envelope form in which the gamma-carbon atom deviates from the plane of the remaining four atoms in the ring.     

X-ray studies on crystalline complexes involving amino acids and peptides. Part XX. Crystal structures of DL-arginine acetate monohydrate and DL-lysine acetate and a comparison with the corresponding L-amino acid complexes

Crystals of DL-arginine acetate monohydrate, C6H15N4O2+C2H3O2-.H2O, are monoclinic, P2(1)/c, with a = 13.552(2), b = 5.048(2), c = 18.837(3) A, beta = 101.34(2) degrees and Z = 4, and those of DL-lysine acetate, C6H15N2O2+.C2H3O2- are triclinic, P1, with a = 5.471(2), b = 7.656(2), c = 12.841(2) A, alpha = 94.48(1), beta = 94.59(2), gamma = 98.83(2) degrees and Z = 2. The structures have been solved by direct methods and refined to R = 0.058 and 0.077 for 1522 and 1259 observed reflections respectively. The difference in the number and the nature of proton donors leads to a difference in hydrogen bond density in the two structures. The basic elements of aggregation in both the structures are pairs of amino acid molecules, each pair stabilized by two centrosymmetrically related hydrogen bonds involving alpha-amino and alpha-carboxylate groups, stacked along the shortest dimension to form columns. The pairs are held together in each column by head-to-tail sequences. The columns stack along a crystallographic axis to form layers. Adjacent layers are bridged by acetate ions. The amino acid-acetate interactions are primarily through side chains and involve specific interactions and characteristic interaction patterns. The gross features of molecular aggregation are nearly the same in DL-arginine acetate monohydrate and L-arginine acetate whereas they are substantially different in the lysine complexes. In both cases, one of the two head-to-tail sequences in the L complex is replaced by a hydrogen bonded loop involving alpha-amino and alpha-carboxylate groups, in the DL complex. This may have implications for prebiotic condensation during chemical evolution.     

X-ray structure, solution properties, and biological activity profile of vanadocene(IV) acetylacetonate complex,

The structure of [V(eta5-C5H5)2(CH3C(O)CHC(O)CH3)](O3SCF3) (1) (=[VCp2(acac)](O3SCF3)), a dual-function anti-cancer agent with anti-angiogenic and anti-mitotic properties, was determined by single-crystal X-ray diffraction. The geometry is well described as a pseudo-tetrahedral like structure with the centroids of the cyclopentadienyl rings and the two oxygen atoms of the acetylacetonate ring in the ancillary positions of the central vanadium (IV) atom. The bisector of the V(acac) fragment deviates from the C2 axis of the ligand framework by only 4 degrees, compared to a deviation of 7 degrees for the V(acac) fragment in the tetramethylethano-bridged vanadocene acetyl acetonate complex. Crystal data for 1: space group, P2(1)/c; a=7.5544(9) A, b=14.936(2) A, c=16.193(2) A, beta=102.901(2) degrees, V= 1781.0(4) A3; Z=4; R=0.0506 for 2310 reflections with I> 2sigma(I). This report also details the electron paramagnetic resonance, UV/Vis spectroscopy, electrochemical properties and the biological activity profile of this potent anti-cancer agent.     

A sequence preference for nucleation of alpha-helix--crystal structure of Gly-L-Ala-L-Val and Gly-L-Ala-L-Leu: some comments on the geometry of leucine zippers

The synthetic peptide Gly-L-Ala-L-Val (C10H19N3O4.3H2O; GAV) crystallizes in the monoclinic space group P21, with a = 8.052(2), b = 6.032(2), c = 15.779(7) A, beta = 98.520(1) degree, V = 757.8 A3, Dx = 1.312 g cm-3, and Z = 2. The peptide Gly-L-Ala-L-Leu (C11H21N3O4.3H2O; GAL) crystallizes in the orthorhombic space group P212121, with a = 6.024(1), b = 8.171(1), c = 32.791(1) A, V = 1614 A3, Dx = 1.289 g cm-3, and Z = 4. Their crystal structures were solved by direct methods using the program SHELXS-86, and refined to an R index of 0.05 for 1489 reflections for GAV and to an R index of 0.05 for 1563 reflections for GAL. The tripeptides exist as a zwitterion in the crystal and assume a near alpha-helical backbone conformation with the following torsion angles: psi 1 = -150.7 degrees; phi 2, psi 2 = -68.7 degrees, -38.1 degrees; phi 3, psi 32 = -74.8 degrees, -44.9 degrees, 135.9 degrees for GAV; psi 1 = -150.3 degrees; phi 2, psi 2 = -67.7 degrees, -38.9 degrees; phi 3, psi 31, psi 32 = -72.2 degrees, -45.3 degrees, 137.5 degrees for GAL. Both the peptide units in both of the tripeptides show significant deviation from planarity [omega 1 = -171.3(6) degrees and omega 2 = -172.0(6) degrees for GAV; omega 1 = -171.9(5) degrees and omega 2 = -173.2(6) degrees for GAL]. The side-chain conformational angles chi 21 and chi 22 are -61.7(5) degrees and 175.7(5) degrees, respectively, for valine, and the side-chain conformations chi 12 and chi 23's are -68.5(5) degrees and (-78.4(6) degrees, 159.10(5) degrees) respectively, for leucine. Each of the tripeptide molecule is held in a near helical conformation by a water molecule that bridges the NH3+ and COO- groups, and acts as the fourth residue needed to complete the turn by forming two hydrogen bonds. Two other water molecules form intermolecular hydrogen bonds in stabilizing the helical structure so that the end result is a column of molecules that looks like an alpha-helix.     

Helix aggregation in peptide crystals: occurrence of either all parallel or antiparallel packing motifs for alpha-helices in polymorphs of Boc-Aib-Ala-Leu-Ala-Leu-Aib-Leu-Ala-Leu-Aib-OMe

Three crystalline polymorphs of the helical decapeptide, Boc-Aib-Ala-Leu-Ala-Leu-Aib-Leu-Ala-Leu-Aib-OMe, have been obtained. Antiparallel helix aggregation is observed in crystals grown from methanol (A), while completely parallel packing is observed in crystals from isopropanol (B) or an ethylene glycol-ethanol mixture (C). Crystals B and C are very similar in molecular conformation and packing. The packing motifs in crystals A and B consist of rows of parallel molecules, with an almost identical arrangement in both crystals. In crystal A, adjacent rows assemble with the helix axes pointed in opposite directions, whereas in crystal B all rows assemble with helix axes pointed in the same direction. Electrostatic interactions between helix dipoles do not appear to be a major determinant of packing modes. The structures also do not provide a ready rationalization of packing preferences in terms of side-chain interactions or solvation. The alpha-helix of the peptide in crystal A has seven 5----1 hydrogen bonds; the helix in crystal B is a mixed 3(10)/alpha-helix. The crystal parameters are as follows. Crystal A: C51H92N10O13.CH3OH, space group P2(1) with a = 10.498 (1) A, b = 18.189 (3) A, c = 16.475 (3) A, beta = 99.28 (1) degree, Z = 2, R = 9.6% for 1860 data. Crystal B: C51H92N10O13.C3H7OH, space group P2(1) with a = 10.534 (1) A, b = 28.571 (4) A, c = 11.055 (2) A, beta = 95.74 (1) degree, Z = 2, R = 6.5% for 3251 data. Crystal C: C51H92N10O13.C2H5OH, space group P2(1), with a = 10.450 (1) A, b = 28.442 (5) A, c = 11.020 (2) A, beta = 95.44(1) degree, Z = 2, R = 14.8% (isotropic) for 1948 data.     

Design of peptides: synthesis, crystal structure, molecular conformation, and conformational calculations of N-Boc-L-Phe-Dehydro-Ala-OCH3.

It is noteworthy that the dehydro-Ala residue adopts an extended conformation that is different than those observed in dehydro-Phe, dehydro-Leu, and dehydro-Abu. The peptide N-Boc-L-Phe-dehydro-Ala-OCH3 (C18H24N2O5) was synthesized by the usual workup procedure and finally by converting N-Boc-L-Phe-L-Ser-OCH3 to N-Boc-L-Phe-dehydro-Ala- OCH3. It was crystallized from its solution in a methanol-water mixture at room temperature. The crystals belong to the monoclonic space group P2(1), with a = 9.577(1) A, b = 5.195(3) A, c = 19.563(3) A, beta = 94.67(5) degrees, V = 970.1(6) A3, Z = 2, dm = 1.201(5) Mg m-3, dc = 1.197(5) Mg m-3. The structure was determined using direct method procedures. It was refined by a full-matrix least-squares procedure to an R value of 0.048 for 1370 observed reflections. The C2 alpha-C2 beta distance is 1.327(8) A, while the bond angles N2-C2 alpha-C2' and C1'-N2-C2 alpha are 109.8(5) degrees and 127.8(5) degrees, respectively. The backbone adopts a nonspecific conformation with dehydro-Ala in a fully extended conformation with the following torsion angles: theta 1 = 175.2(4) degrees, omega 0 = 170.2(4) degrees, phi 1 = 135.8(5) degrees, psi 1 = -22.6(6) degrees, omega 1 = 168.5(5) degrees, phi 2 = -170.3(5) degrees, psi 2T = -178.6(5) degrees, theta T = 178.4(7) degrees. The rigid planar and trans conformation of dehydro-Ala forces Phe to adopt a strained conformation. The Boc group has a trans-trans conformation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Absolute configuration of Rp-uridine 3'',5''-cyclic phosphorothioate.

Triethylammonium uridine-3',5'-cyclic phosphorothioate crystallizes in space group P2(1)2(1)2(1), a = 7.177(1), b = 13.155(6), c = 21.114(7) A, C15H26N3O7PS, MW 423.4, Z = 4, dx = 1.41g/cm3. The crystal structure was solved by direct methods on the basis of 1493 counter X-ray diffraction data (CuK alpha) and refined to R = 5.1%. The configuration of the thiophosphate group is Rp; conformational parameters are: glycosyl torsion angle anti, -151.9(5) degrees, sugar pucker C(3')-endo with P = 27.3 degrees, vmax = 45.5 degrees, six-membered cycle in chair form. The bond distances in the non-esterified P-S and P-O suggest that the negative charge is distributed between the groups. As illustrated in this and other studies, P-O has a much higher affinity for hydrogen bonds than P-S, indicated here by interactions with triethyl-ammonium N-H and O(2')-H as donors. One additional hydrogen bond N(3)-H---0(4) ties the bases which form a ribbon-like structure. 0(2) and S are not engaged in hydrogen bonds. The triethylammonium ion is two-fold disordered.     

Modular design of synthetic protein mimics. Characterization of the helical conformation of a 13-residue peptide in crystals

The incorporation of alpha-aminoisobutyryl (Aib) residues into peptide sequences facilitates helical folding. Aib-containing sequences have been chosen for the design of rigid helical segments in a modular approach to the construction of a synthetic protein mimic. The helical conformation of the synthetic peptide Boc-Aib-(Val-Ala-Leu-Aib)3-OMe in crystals is established by X-ray diffraction. The 13-residue apolar peptide adopts a helical form in the crystal with seven alpha-type hydrogen bonds in the middle and 3(10)-type hydrogen bonds at either end. The helices stack in columns, zigzag rather than linear, by means of direct NH...OC head to tail hydrogen bonds. Leucyl side chains are extended on one side of the helix and valyl side chains on the other side. Water molecules form hydrogen bonds with several backbone carbonyl oxygens that also participate in alpha-helix hydrogen bonds. There is no apparent distortion of the helix caused by hydration. The space group is P2(1)2(1)2(1), with a = 9.964 (3) A, b = 20.117 (3) A, c = 39.311 (6) A, Z = 4, and dx = 1.127 g/cm3 for C64H106N13O16.1.33H2O. The final agreement factor R was 0.089 for 3667 data observed greater than 3 sigma(F) with a resolution of 0.9 A.     

Syntheses,characterization and X-ray structures of the fac-[RuCl3(NO)(dppe)] and the trans-[RuCl(NO)(dppe)2]2+ species

Trans-[RuCl(NO)(dppe)2]2+ species were prepared. The complexes have been characterized by microanalysis, IR and 31P[1H] NMR spectroscopy and cyclic voltammetry. The trans-[RuCl(NO)(dppe)2](ClO4)2 complex shows a reversible one-electron-reduction process at E(1/2) = 0.200 V and another one-electron-reduction irreversible process at -0.620 V, both centered at the NO+ group. The dissociation of the NO group from the trans-[RuCl(NO)(dppe)2]2+ after two one-electron reductions results in the formation of the trans- and cis-[RuCl2(dppe)2] isomers. The product of an electrolyzed solution of the same complex at -0.300 V shows an EPR signal consistent with the presence of the [RuCl(NO(0))(dppe)2]+ complex. Crystal data for trans-[RuCl(NO)(dppe)2]2+*[RuCl4(NO)(H2O)]*1/2[RuCl6]4-*2[H2O] (I) and trans-[RuCl(NO)(dppe)(2)]2+*2[RuCl4(NO)(CH3O)]-*3[CH3OH] (II) are as follow: (I) Space group P-1, a=10.4040(3) A, b=12.3470(4) A, c=23.5620(8) A, alpha=95.885(2) degrees, beta=99.608(2) degrees, gamma=104.378(2) degrees, R=0.0521; (II) space group P-1, a=10.9769(2) A, b=13.2753(3) A, c=24.0287(4) A, alpha=99.743(1) degrees, beta=95.847(1) degrees, gamma=97.549(1) degrees; R=0.0496. The fac-[RuCl3(NO)(dppe)] (III) complex has been also prepared; its crystal data are: space group P2(1)/n (No. 14), a=11.841(2) A, b=13.775(2) A, c=16.295(4) A, beta=92.81(2) degrees; R1=0.0395.     

N-Benzoyl-N'-dialkylthiourea derivatives and their Co(III) complexes: structure, and antifungal

N-(Morpholinothiocarbonyl) benzamide (C(12)H(14)N(2)O(2)S) and N-(piperidylthiocarbonyl) benzamide (C(13)H(16)N(2)OS) and their Co(III) complexes have been synthesized and characterized by elemental analysis, FTIR and NMR methods. The complex Co(C(12)H(14)N(2)O(2)S)(3), crystallizes in the triclinic space group P1, with Z=2, and unit cell parameters, a=12.080(7)A, b=12.195(7)A, c=13.025(6)A, alpha=90.198(7) degrees, beta=95.721(7) degrees, gamma=106.426(9) degrees, V=1830.4(17)A(3). The antifungal activity against the major pathogens responsible for important plant diseases (Botrytis cinerea, Myrothecium and Verticillium dahliae dleb) of N-(piperidylthiocarbonyl) benzamide and its complex with cobalt (III) are studied and compared with N-(morpholinothiocarbonyl) benzamide.