Sofa Conformation Research Articles

2-Amino-4-(4-chloro-1-ethyl-2,2-dioxo-1H-benzo[c][1,2]thia-zin-3-yl)-7,7-dimethyl-5-oxo-5,6,7,8-tetra-hydro-4H-chromene-3-carbo-nitrile: single-crystal X-ray diffraction study and Hirshfeld surface analysis.

In the title compound, C22H22ClN3O4S, which has potential non-steroidal anti-inflammatory activity, the benzo-thia-zine and cyclo-hexenone rings both adopt a distorted sofa conformation while the 4H-pyrane ring adopts a very flattened sofa conformation. The two bicyclic fragments are skewed to each other, with the dihedral angle between their least-squares planes being 72.8 (1)°. In the crystal, the mol-ecules form a hydrogen-bonded chain parallel to the a axis due to N-H⋯O and N-H⋯Cl hydrogen bonds. Neighbouring chains are linked by C-H⋯N, C-H⋯O and π-π stacking inter-actions. Hirshfeld surface analysis was used to investigate the importance of the different types of inter-molecular inter-actions whose contributions are: H⋯H = 44.7%, O⋯H/H⋯O = 21.8%, N⋯H/H⋯N = 11.9%, C⋯H/H⋯C = 9.5%, Cl⋯H/H⋯Cl = 7.2%. Parts of the mol-ecule, viz. the phenyl ring and the ethyl side chain, are equally disordered over two sets of sites.

Synthesis, crystal structure, Hirshfeld surface, DFT calculations, Z-scan and nonlinear optical studies of novel flourinated hexahydropyrimidine

A new fluorinated hexahydropyrimidine was synthesized and its crystal structure was elucidated using single crystal X-ray diffraction technique. This compound, C15H17F3N2O6 crystallizes in monoclinic space group P21/c with cell parameters a = 10.6345(3) Å, b = 14.7074(4) Å, c = 10.6677(4) Å, β= 101.453(2)° and V= 1635.27 (9) Å3. In this compound the hexahydropyrimidine ring (C7/C8/C12/N1/C14/N2) adopts sofa conformation. The puckering parameters are Q = 0.5117Å, Ɵ = 129.59° and φ =304.0802°. The analysis of Hirshfeld surface indicates the presence of hydrogen bonds C‒H•••F, C‒H•••O, O‒H•••O, N‒H•••O and π•••π stacking stabilizes the system. The energy optimized structure was calculated using Density Functional Theory (DFT) and were employed by hybrid functional theory (B3LYP) at 6-311++G(d,p) basis set in the Gaussian09_revision C0.1 program package. The natural bond orbital analysis results state that the highest energy transfer of 604.21 kJ/mol occur between the donor σ(O4‒H43) to acceptor σ*(C34‒H36) through carboxylate chain. Moreover, the vibrational assignments, global reactivity descriptors, energy gap and molecular electrostatic potential (MEP) also gives clear insight about chemical and biological activity of the molecule. The first hyperpolarizability value 7.2987 × 10−30 esu of the synthesized compound is twenty times greater than that of urea (0.3728 × 10−30 esu). The one electron excitation of the synthesized crystal calculated by the time dependent-density functional theory (TD-DFT) calculation and comparatively studied using recorded UV spectrum. The single beam Z-scan unit equipped with 532 nm continuous Nd:YAG wave laser with 5ns pulse width was used to measure third order nonlinear optical property reveal that the investigated molecule possess effective two photon absorption with higher effective absorption coefficient. The imaginary and real parts of the third-order susceptibility values determined as Im χ3 = 2.31 × 10−6 cm W−1 and Re χ3 = 8.74 × 10−8 cm2 W−1 respectively.

Exploiting a C–N Bond Forming Cytochrome P450 Monooxygenase for C–S Bond Formation

AbstractC–S bond formation reactions are widely distributed in the biosynthesis of biologically active molecules, and thus have received much attention over the past decades. Herein, we report intramolecular C–S bond formation by a P450 monooxygenase, TleB, which normally catalyzes a C−N bond formation in teleocidin biosynthesis. Based on the proposed reaction mechanism of TleB, a thiol‐substituted substrate analogue was synthesized and tested in the enzyme reaction, which afforded the unprecedented sulfur‐containing thio‐indolactam V, in addition to an unusual indole‐fused 6/5/8‐tricyclic product whose structure was determined by the crystalline sponge method. Interestingly, conformational analysis revealed that the SOFA conformation is stable in thio‐indolactam V, in sharp contrast to the major TWIST form in indolactam V, resulting in differences in their biological activities.

Exploiting a C–N Bond Forming Cytochrome P450 Monooxygenase for C–S Bond Formation

C-S bond formation reactions are widely distributed in the biosynthesis of biologically active molecules, and thus have received much attention over the past decades. Herein, we report intramolecular C-S bond formation by a P450 monooxygenase, TleB, which normally catalyzes a C-N bond formation in teleocidin biosynthesis. Based on the proposed reaction mechanism of TleB, a thiol-substituted substrate analogue was synthesized and tested in the enzyme reaction, which afforded the unprecedented sulfur-containing thio-indolactam V, in addition to an unusual indole-fused 6/5/8-tricyclic product whose structure was determined by the crystalline sponge method. Interestingly, conformational analysis revealed that the SOFA conformation is stable in thio-indolactam V, in sharp contrast to the major TWIST form in indolactam V, resulting in differences in their biological activities.

Synthesis and structural study of organic two-photon-absorbing cycloalkanone chromophores.

The three organic two-photon-absorbing cycloalkanone chromophores 2,4-bis[4-(diethylamino)benzylidene]cyclobutanone, C26H32N2O (I), 2,5-bis[4-(diethylamino)benzylidene]cyclopentanone, C27H34N2O (II), and 2,6-bis[4-(diethylamino)benzylidene]cyclohexanone, C28H36N2O (III), were obtained by a reaction between 4-(diethylamino)benzaldehyde and the corresponding cycloalkanone and were characterized by single-crystal X-ray diffraction studies, as well as density functional theory (DFT) quantum-chemical calculations. Molecules of this series have three main fragments, i.e. central acceptor (A) and two terminal donors (D1 and D2) and represent examples of the D1-π-A-π-D2 molecular design. All three compounds crystallize with two crystallographically independent molecules in the asymmetric unit (A and B) and are distinguished by the conformations of both the molecular Et2N-C6H4-C=C-C(=O)-C=C-C6H4-NEt2 backbone (arcuate or linear) and the terminal diethylamino substituents (syn- or antiperiplanar to the plane of the molecule). The central four- and five-membered rings in I and II are almost planar, and the six-membered ring in III adopts a sofa conformation. In the crystals of I-III, the two independent molecules A and B form hydrogen-bonded [A...B] dimers via intermolecular C-H...O hydrogen bonds. Furthermore, the [A...B] dimers in I are bound by intermolecular C-H...O hydrogen bonds into two-tier puckered layers, whereas in the crystals of II and III, the [A...B] dimers are stacked along the c and a axes, respectively. Taking into account the decreasing steric strain upon expanding the central ring, compound I might be more efficient as a two-photon absorption chromophore than compounds II and III, which corresponds to the results of spectroscopic studies.

Crystal and Molecular Structure and DFT Calculations of the Steroidal Oxime 6E-Hydroximino-androst-4-ene-3,17-dione (C19H25NO3) a Molecule with Antiproliferative Activity

The single crystal X-ray structure of the novel steroid derivative, 6E-hydroximino-androst-4-ene-3,17-dione (C19H25NO3) (code name RB-499), possessing antiproliferative activity against various cell lines is presented. The analysis produced the following results: chemical formula C19H25NO3; Mr = 315.40; crystals are orthorhombic space group P212121 with Z = 4 molecules per unit cell with a = 6.2609(2), b = 12.5711(4), c = 20.0517(4) Å,Vc = 1578.18(7) Å3, crystal density Dc = 1.327 g/cm³. Structure determination was performed by direct methods, Fourier and full-matrix least-squares refinement. Hydrogens were located in the electron density and refined in position with isotropic thermal parameters. The final R-index was 0.0324 for 3140 reflections with I > 2σ and 308 parameters. The Absolute Structure Parameter − 0.07(5) confirms the correct allocation of the absolute configuration. The presence of the double bond C=O at position 3 in Ring A has caused a distortion from the usual chair conformation and created an unusual distorted sofa conformation folded across an approximate m-plane through C(1)–C(4). Ring B is a distorted chair, its conformation being influenced by the presence of the C(6)=N(6)–O(6)H group in position 6. Ring C is a symmetrical chair. Ring D exhibits both a distorted mirror symmetry conformation [influenced by the C(17)=O(17) group] and a distorted twofold conformation. DFT calculations indicated some degree of flexibility in rings A, C and D with ring A showing the greatest variation in torsion angles. The crystal packing is governed by H-bonds involving O(3), O(6) and O(17). DFT calculations of bond distances and angles, optimized at the B3LYP/6–31++G(d,p) level, were in good agreement with the X-ray structure.Graphical Ring A conformations: (a) Experimental and (b) Calculated. The differences in torsion angle values indicate a degree of flexibility in the ring. The ring conformations are shown in Figures (ii) and (iv) respectively (drawn with BIOVIA [12]. Regions A1 and A2 are approximately planar in both, being planar within 0.048 Å and 0.105 Å respectively.

(3E)-3-{(2E)-3-[4-(Dimethylamino)phenyl]prop-2-enylidene}-3,4-dihydro-2H-chromen-4-one

In the title compound, C20H19NO2, the (dimethylamino)phenyl ring and the chromanone ring system are linkedviaan α-β unsaturated carbon bridge. The dihedral angle between the two terminal phenyl rings is 29.66 (6)°. The tetrahydro-4H-pyran-4 one ring in the chromanone moiety adopts a sofa conformation. The crystal packing is stabilized only by van der Waals forces.

Three-component reaction between isatoic anhydride, amine and meth-yl-subs-tituted furyl-acryl-alde-hydes: crystal structures of 3-benzyl-2-[(E)-2-(5-methylfuran-2-yl)vin-yl]-2,3-di-hydro-quinazolin-4(1H)-one, 3-benzyl-2-[(E)-2-(furan-2-yl)-1-methyl-vin-yl]-2,3-di-hydro-quinazolin-4(1H)-one and 3-(furan-2-ylmeth-yl)-2-[(E)-2-(furan-2-yl)-1-methyl-vin-yl]-2,3-di-hydro-quinazolin-4(1H)-one.

Compounds (I), C22H20N2O2, (II), C22H20N2O2 and (III), C20H18N2O3 are the products of three-component reactions between isatoic anhydride, the corresponding amine and 3-(5-methylfuran-2-yl)- or (furan-2-yl)-2-methyl-acryl-aldehyde. Compound (I) crystallizes in the monoclinic space group P21/n, while compounds (II) and (III) are isostructural and crystallize in the ortho-rhom-bic space group Pbca. The tetra-hydro-pyrimidine ring in (I)-(III) adopts a sofa conformation. The NH nitro-gen atom has a trigonal-pyramidal geometry, whereas the N(R) nitro-gen atom is flattened. The furyl-vinyl substituents in (I)-(III) are practically planar and have an E configuration at the C=C double bond. In (I), this bulky fragment occupies the axial position at the quaternary carbon atom of the tetra-hydro-pyrimidine ring, whereas in (II) and (III) it is equatorially disposed. In the crystal of (I), mol-ecules form hydrogen-bonded chains propagating along [001] by strong inter-molecular N-H⋯O hydrogen bonds. The chains are packed in stacks along the a-axis direction. In the crystals of (II) and (III), mol-ecules also form hydrogen-bonded chains propagating along [100] by strong inter-molecular N-H⋯O hydrogen bonds. However, despite the fact that compounds (II) and (III) are isostructural, steric differences between the phenyl and furyl substituents result in chains with different geometries. Thus in the crystal of (II) the chains have a zigzag-like structure, whereas in the crystal of (III), they are almost linear. In both (II) and (III), the hydrogen-bonded chains are further packed in stacks along the b-axis direction.

Crystal structure of 3-hy-droxy-2-(4-hy-droxy-3-meth-oxy-phenyl-methyl)-5,5-di-methyl-cyclo-hex-2-enone.

In the title compound, C16H20O4, a new starting compound for the synthesis of various heterocycles, the partially saturated six-membered ring adopts a sofa conformation. An intra-molecular O-H⋯O hydrogen bond is observed in the guaiacol residue. In the crystal, mol-ecules are assembled into a sheet structure parallel to the ab plane via O-H⋯O hydrogen bonds. The hydrogen-bond pattern is described by an R44(28) graph-set motif. The sheets are further linked by C-H⋯O hydrogen bonds into a three-dimensional network.

Further investigation on the nitration of BODIPY with cupric nitrate: crystal structures of 4,4-di-fluoro-1,3,5,7,8-penta-methyl-2-nitro-4-bora-3a,4a-di-aza-s-indacene, 4,4-di-fluoro-3-nitro-8-phenyl-4-bora-3a,4a-di-aza-s-indacene, and 3-chloro-6-ethyl-5,7,8-trimethyl-2-nitro-4,4-diphenyl-4-bora-3a,4a-di-aza-s-indacene.

The treatment of non-fully substituted 4,4-di-fluoro-4-bora-3a,4a-di-aza-s-indacene (BODIPY) with cupric nitrate leads to the introduction of a nitro group at different positions of the BODIPY core, depending on the substitution pattern. This methodology complements the treatment of fully substituted BODIPY with cupric nitrate that was previously reported. The crystal structures of 4,4-di-fluoro-1,3,5,7,8-penta-methyl-2-nitro-4-bora-3a,4a-di-aza-s-indacene, C14H16BF2N3O2 (5a) 4,4-di-fluoro-3-nitro-8-phenyl-4-bora-3a,4a-di-aza-s-indacene, C15H10BF2N3O2(5b) and 3-chloro-6-ethyl-5,7,8-trimethyl-2-nitro-4,4-diphenyl-4-bora-3a,4a-di-aza-s-indacene, C26H25BClN3O2 (5d) are presented. In all three structures, the fused ring system is in a very flattened 'V-shape', with dihedral angles between the two outer five membered rings of 8.12 (14), 6.67 (9) and 12.30 (18) Å for 5a, 5b and 5d, respectively. In each case, the central six-membered ring is in a flattened sofa conformation. In the crystal of 5a, mol-ecules are linked by weak C-H⋯O and C-H⋯F hydrogen bonds forming sheets parallel to (10-1). In the crystal of 5b mol-ecules are linked by weak C-H⋯O and C-H⋯F hydrogen bonds and π-π inter-actions forming sheets parallel to (001). In the crystal of 5d, weak C-H⋯O hydrogen bonds link mol-ecules into chains along [001]. In compound 5d, the atoms of the nitro group were refined as disordered over two sets of sites with occupancies 0.618 (12) and 0.382 (12).

Crystal structure of 3-benzyl-2-[(E)-2-(furan-2-yl)ethen-yl]-2,3-di-hydro-quinazolin-4(1H)-one and 3-benzyl-2-[(E)-2-(thio-phen-2-yl)ethen-yl]-2,3-di-hydro-quinazolin-4(1H)-one from synchrotron X-ray diffraction.

The chiral title compounds, C21H18N2O2, (I), and C21H18N2OS, (II) - products of the three-component reaction between benzyl-amine, isatoic anhydride and furyl- or thienyl-acrolein - are isostructural and form isomorphous racemic crystals. The tetra-hydro-pyrimidine ring in (I) and (II) adopts a sofa conformation. The amino N atom has a trigonal-pyramidal geometry [sum of the bond angles is 347.0° for both (I) and (II)], whereas the amido N atom is flat [sum of the bond angles is 359.3° for both (I) and (II)]. The furyl- and thienylethenyl substituents in (I) and (II) are planar and the conformation about the bridging C=C bond is E. These bulky fragments occupy the axial position at the quaternary C atom of the tetra-hydro-pyrimidine ring, apparently, due to steric reasons. In the crystals, mol-ecules of (I) and (II) form hydrogen-bonded helicoidal chains propagating along [010] by strong inter-molecular N-H⋯O hydrogen bonds.

Crystal structure of 3,6,6-trimethyl-4-oxo-1-(pyridin-2-yl)-4,5,6,7-tetra-hydro-1H-indazol-7-aminium chloride and its monohydrate.

The title compounds, C15H19N4O+·Cl- and C15H19N4O+·Cl-·H2O, obtained in attempts to synthesize metal complexes using tetra-hydro-indazole as a ligand, were characterized by NMR, IR and X-ray diffraction techniques. The partially saturated ring in the tetra-hydro-indazole core adopts a sofa conformation. An intra-molecular N-H⋯N hydrogen bond formed by the protonated amino group and the N atom of the pyridyl substituent is found in the first structure. In the hydro-chloride, the organic moieties are linked by two N-H⋯Cl- hydrogen bonds, forming a C(4) graph-set. In the hydrate crystal, a Cl- anion and a water mol-ecule assemble the moieties into infinite bands showing hydrogen-bond patterns with graph sets C(6), R64(12) and R42(8). Organic moieties form π-π stacked supra-molecular structures running along the b axis in both structures.

Conformational analysis of 2-isopropyl-5-methyl-5-methoxymethyl-1,3,2-dioxaborinane

Study of conformational transformations of 2-isopropyl-5-methyl-5-methoxymethyl-1,3,2-dioxaborinane using DFT approximation PBE/3ζ and the second order perturbation theory method RI-MP2/λ2 revealed beside the interconversion route sofa–sofa through a transition state corresponding to 2,5-twist form a number of local minima due to internal rotation of isopropyl and methoxymethyl substituents in sofa conformers. Over 88% of the molecules of the studied compound are present in a sofa form with the equatorially oriented CH2OCH3 group.

Structure of Equilenin at 100 K: an estrone-related steroid.

The structure of the estrone-related steroid, Equilenin, C18H18O2 (systematic name 3-hy-droxy-13-methyl-11,12,13,14,15,16-hexa-hydro-cyclo-penta-[a]phen-anthren-17-one), has been determined at 100 K. The crystals are ortho-rhom-bic, P212121, and the absolute structure of the mol-ecule in the crystal has been determined by resonant scattering [Flack parameter = -0.05 (4)]. The C atoms of the A and B rings are almost coplanar, with an r.m.s. deviation from planarity of 0.0104 Å. The C ring has a sofa conformation, while the D ring has an envelope conformation with the methine C atom as the flap. The keto O atom and the methyl group are translated 0.78 and 0.79 Å, respectively, from the equivalent positions on 17β-estrone. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, forming chains parallel to the c-axis direction.

Ethyl 2-[9-(5-bromo-2-hydroxyphenyl)-3,3,6,6-tetramethyl-1,8-dioxo-1,2,3,4,5,6,7,8,9,10-decahydroacridin-10-yl]acetate

In the title compound, C27H32BrNO5, the central 1,4-dihydropyridine ring adopts a shallow sofa conformation (with the C atom bearing the bromophenol ring as the flap), whereas the pendant cyclohexene rings both have twisted-boat conformations. The molecule features an intramolecular O—H...O hydrogen bond, which closes anS(8) ring. In the crystal, molecules are linked by C—H...O interactions, formingC(12) chains along thec-axis direction. The ethyl acetate grouping is disordered over two sets of sites in a 0.719 (11):0.281 (11) ratio.

Molecular and crystal structure of 4-dichloromethylene-5-benzoyl-6-phenyl-perhydropyrimidin-2-one and its N(1)-substituted analogue

A single crystal X-ray diffraction analysis of 4-dichloromethylene-5-benzoyl-6-phenyl-perhydropyrimidin-2-one and its functionally substituted analogue with a methylcarbonyl substituent at the N(1) atom in the heterocycle is performed. The molecules of both compounds have two chiral centers. Only rel(S,R)-diastereomers are found in the crystals (the crystals are centrosymmetric). In the 4-dichloromethylene-5-benzoyl-6-phenyl-perhydropyrimidin-2-one molecule the heterocycle is in the С(6)-sofa conformation, whereas the molecule of the substituted analogue has a distorted boat conformation. Due to classical hydrogen bonds there are 1D and 0D supramolecular structures in the crystals of the studied compounds. Interactions of the С–H⋯O type, which only stabilize the structure of already formed associates rather than link the chains or dimers with each other, are also noted.

Crystal structure and solvent-dependent behaviours of 3-amino-1,6-diethyl-2,5,7-trimethyl-4,4-di-phenyl-3a,4a-di-aza-4-bora-s-indacene.

In the title compound (3-amino-4,4-diphenyl-BODIPY), C28H32BN3, the central six-membered ring has a flattened sofa conformation, with one of the N atoms deviating by 0.142 (4) Å from the mean plane of the other five atoms, which have an r.m.s. deviation of 0.015 Å. The dihedral angle between the two essentially planar outer five-membered rings is 8.0 (2)°. In the crystal, mol-ecules are linked via weak N-H⋯π inter-actions, forming chains along [010]. The com-pound displays solvent-dependent behaviours in both NMR and fluorescence spectroscopy. In the 1H NMR spectra, the aliphatic resonance signals virtually coalesce in solvents such as chloro-form, di-chloro-methane and di-bromo-ethane; however, they are fully resolved in solvents such as dimethyl sulfoxide (DMSO), methanol and toluene. The excitation and fluorescence intensities in chloro-form decreased significantly over time, while in DMSO the decrease is not so profound. In toluene, the excitation and fluorescent intensities are not time-dependent. This behaviour is presumably attributed to the assembly of 3-amino-4,4-diphenyl-BODIPY in solution that leads to the formation of noncovalent structures, while in polar or aromatic solvents, the formation of these assemblies is disrupted, leading to resolution of signals in the NMR spectra.

Structure and conformational analysis of 2-hydroxy-5-isobutyl-1,3,2-dioxaborinane

The structure of 2-hydroxy-5-isobutyl-1,3,2-dioxaborinane, one of the major autooxidation products of 5-isobutyl-2-isopropyl-1,3,2-dioxaborinane, has been studied by 1H, 13C, and 11B NMR spectroscopy together with X-ray analysis. Molecules of the title compounds adopt a sofa conformation with equatorial isobutyl substituent. The ring interconversion path, free conformational energy, and optimal conformation of the isobutyl group (corresponding to the X-ray diffraction data) were determined by DFT quantum chemical calculations at the PBE/3ξ level of theory.

Crystal structure of methyl 1-allyl-4-methyl-1H-benzo[c][1,2]thia-zine-3-carboxyl-ate 2,2-dioxide.

In the title compound, C14H15NO4S, the di-hydro-thia-zine ring adopts a distorted sofa conformation with the S atom displaced from the mean plane through the N and C ring atoms by 0.767 (1) Å. The allyl substituent (C-C=C) is inclined to this mean plane by 78.5 (7)° and the acetate group [C(=O)-O-C] by 66.5 (3)°. In the crystal, mol-ecules are linked by C-H⋯π inter-actions forming chains propagating along the a-axis direction.

Crystal Structure Analysis of 3-(4-ethylphenyl)-3H-chromeno[4,3-c]isoxazole-3a(4H)-carbonitrile

The crystal structure of the potential active 3-(4-ethylphenyl)-3H-chromeno[4,3-c]isoxazole-3a(4H)-carbonitrile (<TEX>$C_{19}H_{16}N_2O_2$</TEX>) has been determined from single crystal X-ray diffraction data. In the title compound crystallizes in the monoclinic space group <TEX>$P2_1/c$</TEX> with unit cell dimension a=6.6869 (8) <TEX>${\AA}$</TEX>, b=15.8326 (19) <TEX>${\AA}$</TEX> and c= 15.237 (2) <TEX>${\AA}$</TEX> [<TEX>${\alpha}=90^{\circ}$</TEX>, <TEX>${\beta}=100.663^{\circ}$</TEX> and <TEX>${\gamma}=90^{\circ}$</TEX>]. In the structure chromene, isoxazole and carboxylate are almost coplanar each other. All geometrical parameters revelled that chromene ring of pyran ring adopt sofa conformation. The crystal packing is stabilized by intermolecular C-H...N and C-H...O hydrogen bond interaction.