Major Intermolecular Interactions Research Articles

Synthesis and crystal structures of N,2,4,6-tetra-methyl-anilinium tri-fluoro-methane-sulfonate and N-iso-propyl-idene-N,2,4,6-tetra-methyl-anilinium tri-fluoro-methane-sulfonate.

Two 2,4,6-tri-methyl-aniline-based trifuloro-methane-sulfonate (tri-fluoro-methane-sulfonate) salts were synthesized and characterized by single-crystal X-ray diffraction. N,2,4,6-Tetra-methyl-anilinium tri-fluoro-methane-sulfonate, [C10H14NH2 +][CF3O3S-] (1), was synthesized via methyl-ation of 2,4,6-tri-methyl-aniline. N-Iso-propyl-idene-N,2,4,6-tetra-methyl-anilinium tri-fluoro-meth-ane-sulfonate, [C13H20N+][CF3O3S-] (2), was synthesized in a two-step reaction where the imine, N-iso-propyl-idene-2,4,6-tri-methyl-aniline, was first prepared via a dehydration reaction to form the Schiff base, followed by methyl-ation using methyl tri-fluoro-methane-sulfonate to form the iminium ion. In compound 1, both hydrogen bonding and π-π inter-actions form the main inter-molecular inter-actions. The primary inter-action is a strong N-H⋯O hydrogen bond with the oxygen atoms of the tri-fluoro-methane-sulfonate anions bonded to the hydrogen atoms of the ammonium nitro-gen atom to generate a one-dimensional chain. The [C10H14NH2 +] cations form dimers where the benzene rings form a π-π inter-action with a parallel-displaced geometry. The separation distance between the calculated centroids of the benzene rings is 3.9129 (8) Å, and the inter-planar spacing and ring slippage between the dimers are 3.5156 (5) and 1.718 Å, respectively. For 2, the [C13H20N+] cations also form dimers as in 1, but with the benzene rings highly slipped. The distance between the calculated centroids of the benzene rings is 4.8937 (8) Å, and inter-planar spacing and ring slippage are 3.3646 (5) and 3.553 Å, respectively. The major inter-molecular inter-actions in 2 are instead a series of weaker C-H⋯O hydrogen bonds [C⋯O distances of 3.1723 (17), 3.3789 (18), and 3.3789 (18) Å], an inter-action virtually absent in the structure of 1. Fluorine atoms are not involved in strong directional inter-actions in either structure.

Influence of solvation on the spectral, molecular structure, and antileukemic activity of 1-benzyl-3-hydroxy-2-methylpyridin-4(1H)-one

This research focuses on the synthesis, X-ray crystallography, spectral characterization, and the influence of solvents on electronic molecular properties, vibrational analysis, and electronic excitation along with molecular modeling investigation of 1-benzyl-3-hydroxy-2-methylpyridin-4(1H)-one (BHM) as a potential anti-cancer agent. The electronic properties were investigated using density functional theory (DFT) computation at the B3LYP-GD3BJ/6–311++G(d,p) level in different electronic media: acetone, chloroform, ethanol, and water. The experimental wavenumbers of the 19 most pronounced infrared active bonds juxtaposed by the theoretical wavenumbers in four solvents namely acetone, chloroform, ethanol, and water with their corresponding theoretical intensities. Hirshfeld surface analysis reveals the major intermolecular interactions in the molecule are H⋯H, C⋯H, and O⋯H. The energy gap obtained from the four different solvents (acetone, chloroform, ethanol, and water) shows that BHM has higher reactivity in chloroform with an energy gap of 2.8055 eV as compared to acetone (2.8979 eV), ethanol (2.9035 eV) and water (2.9225 eV). In-silico molecular modeling showed that BHM possesses good anticancer potency with computed mean binding affinities of −3.8, −5.3, and −4.7 for the different tested leukemic targets and therefore, suggesting the applicability of BHM as an effective therapeutic agent for cancer.

DFT guided substitution effect on azomethine reactive center in newly synthesized Schiff base aromatic scaffolds; syntheses, characterization, single crystal XRD, Hirshfeld surface and crystal void analyses

This paper aims to unfold the effect of substitution (ring A & B) on reactivity of newly synthesized crystalline azomethine linked aromatic compounds/Schiff bases (3a-c). Condensation reaction between 2-iodo-4-chloro substituted aniline with various suitably substituted aromatic aldehydes under acidic catalyzed reaction conditions gave crystalline compounds (3a-c) in good yields. The synthesized compounds were initially investigated in the solid state by single crystal X-ray crystallography besides other structural characterizations. Possible reactivity of azomethine pharmacophore is explained based on the electronic features of attached substituents on the aromatic rings A and B. DFT calculations further backed up the reactivity profile translated for compounds (3a-c) based on electronic grounds, while mechanistic investigation for further chemical reactivity is unfolded via frontier molecular orbital calculations and transition state predictions. Prominent nucleophilic character based on DFT study has been attributed to the halo i,e., -Cl and -I substituents on aromatic ring (ring A) in all the synthesized derivatives (3a-c) with pronounced effect in 3c due to added nucleophilic behavior depicted by cyano substitution in ring B. However, HOMO orbital energy values for (3a-c) predict electron donor behavior of substituents (-CH3, -N(CH3)2, -C=N) on ring B with higher donation capacity predicted for 3b, thus indicating its oxidation in possible chemical transformations. Hirshfeld surface analysis revealed the prevalence of potential van der Waals interactions and hydrogen bonding as major intermolecular interactions in their (3a-c) crystal packings. In addition, crystal void analyses depicted high mechanical stabilities for (3a-c) due to absence of large cavities in their crystal packings. Moreover, reaction scope guided by the joint DFT and electronic explanations for the effect of substituents used on azomethine linkage has also been proposed/predicted as part of the study.

Invariant and Variable Supramolecular Self-Assembly in 6-Substituted Uracil Derivatives: Insights from X-ray Structures and Quantum Chemical Study

In this study, three new 6-(arylthio)uracil derivatives, namely, 6-(phenylthio)pyrimidine-2,4(1H,3H)-dione (1), C10H8N2O2S; 6-(p-tolylthio)pyrimidine-2,4(1H,3H)-dione (2), C11H10N2O2S; and 6-(3,5-dimethylphenylthio)pyrimidine-2,4(1H,3H)-dione (3), C12H12N2O2S, have been synthesized. Single-crystal structures of these compounds reveal an invariant molecular tape contains alternate R22(8) synthons formed by N–H···O hydrogen bonds in 1 and 3. This alternate hydrogen-bonded pattern disappeared in 2; instead, a new synthon is generated. The lattice energy calculation suggests that the methyl-substituted derivatives (2 and 3) have high stabilization energy than compound 1. The electrostatic potential map reveals the difference in the accepting tendency of the carbonyl oxygen. The Hirshfeld surface and 2D-fingerprint plots analyses demonstrate that the major intermolecular interactions come from H···O contacts in 1, and these contacts were reduced due to the presence of methyl substitutions in 2 and 3. This reduction is compensated by the increase of the same amount of H···H contacts in these structures. Further, the PIXEL energy and DFT calculations at the M06-2X-D3/cc-pVTZ level of theory were used to characterize the dimeric topology formed in structures of 1–3. The intermolecular interaction energies of dimers calculated by the PIXEL method were compared with the B97D3/def2-TZVP level of approximation. Although these molecules’ crystal packing is somewhat different, the energy frameworks show similarities on the respective crystal structure’s shortest axis. Furthermore, the nature and strength of various noncovalent interactions such as N–H···O, C–H···O/S/π, π···π, and a chalcogen bond of type C–S···O═C were evaluated using the Bader’s quantum theory of atoms-in-molecules framework.

Water Switched Reversible Thermochromism in Organic Salt of Sulfonated Anil

We report concomitant stoichiomorphs [(4,4′-BPY-2H)2+(SA-SY-H)−2·4H2O] 1 and [(4,4′-BPY-H)+(SA-SY-H)−·4H2O] 2 formed in the same reaction vessel, with formation of 2 following 1. The expeditious formation of 1 with half equivalent of bipyridyl former, attributed to 2-fold bifurcated methoxy assisted hydroxyl-pyridinium synthon, leaves behind the solution with an excess of bipyridyl, resulting in the formation of 2. Organic salts 1 and 2 crystallize as triclinic (P̅1) and monoclinic (P21/c) tetrahydrates, with D3 acyclic non-branched and branched lattice water clusters. Hirshfeld and fingerprint studies reveal reciprocal O–H···H–O and weak dispersive H···H contacts are the major intermolecular interactions responsible for supramolecular aggregation. Interestingly, 1 exhibits reversible thermochromism switched by lattice water, while 2 is not thermochromic. Photochromism in both sulfonated anil based organic salts 1 and 2 is ruled out due to the significantly lower Vfree value than required for the free rotation about the imine bond to generate cis–trans isomers. Keto–enol prototropism-triggered thermochromism is also ruled out because of the intramolecular sulfonate proton shift to the imine nitrogen as well as the position of absorption curves in the Kubelka–Munk plots. The lattice water switched mechanism for reversible thermochromism in 1 is proposed and substantiated by FT-IR, TGA-DTA, DR-UV, and P-XRD studies and further validated by the Tauc plots. To the best of our knowledge, 1 represents the first example of water-triggered all-organic reversible thermochromic material and has been utilized as a thermal sensor for the reflux reactions in low boiling solvents.

3D Printed Calcium Phosphate Cement (CPC) Scaffolds for Anti-Cancer Drug Delivery.

One of the main applications of bone graft materials is filling the gap after the surgical removal of bone cancer or tumors. Insufficient healing commonly leads to non-union fracture which could lead to cancer resurgence or infection. Emerging 3D printing of on-demand bone graft biomaterials can deliver personalized solutions with minimized risk of relapse and recurrence of cancer after bone removal surgery. This research aims to explore 3D printed calcium phosphate cement (CPC) based scaffolds as novel anti-cancer drug delivery systems to treat bone cancer. For the study, various 3D printed CPC based scaffolds (diameter 5 mm) with interconnected pores were utilized. Various optimized polymeric solutions containing a model anticancer drug 5-fluorouracil (5-FU) was used to homogenously coat the CPC scaffolds. Both hydrophilic Soluplus (SOL) and polyethylene glycol (PEG) and a combination of both were used to develop stable coating solutions. The surface morphology of the coated scaffolds, observed via SEM, revealed deposition of the polymeric solution represented by a semi-smooth surface as opposed to the blank scaffolds that showed a smoother surface. An advanced surface analysis conducted via confocal microscopy showed a homogenous distribution of the drug throughout the coated scaffolds. Solid-state analysis studied by applying differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed semi-crystalline nature of the drug whereas mechanical analysis conducted via texture analysis showed no evidence in the change of the mechanical properties of the scaffolds after polymeric solutions were applied. The FTIR analysis revealed no major intermolecular interactions between 5-FU and the polymers used for coatings except for F2 where a potential nominal interaction was evidenced corresponding to higher Soluplus content in the formulation. In vitro dissolution studies showed that almost 100% of the drug released within 2 h for all scaffolds. Moreover, in vitro cell culture using two different cell lines (Hek293T-human kidney immortalized cell line and HeLa-human bone osteosarcoma epithelial cell line) showed significant inhibition of cell growth as a function of decreased numbers of cells after 5 days. It can be claimed that the developed 5-FU coated 3D printed scaffolds can successfully be used as bone graft materials to potentially treat bone cancer or bone neoplasm and for personalized medical solutions in the form of scaffolds for regenerative medicine or tissue engineering applications.

Thiabendazole and Thiabendazole-Formic Acid Solvate: A Computational, Crystallographic, Spectroscopic and Thermal Study.

Thiabendazole (TBZ) is a substance which has been receiving multiple important applications in several domains, from medicine and pharmaceutical sciences, to agriculture and food industry. Here, a comprehensive multi-technique investigation on the molecular and crystal properties of TBZ is reported. In addition, a new solvate of the compound is described and characterized structurally, vibrationally and thermochemically for the first time. Density functional theory (DFT) calculations were used to investigate the conformational space of thiabendazole (TBZ), revealing the existence of two conformers, the most stable planar trans form and a double-degenerated-by-symmetry gauche form, which is ~30 kJ mol−1 higher in energy than the trans conformer. The intramolecular interactions playing the major roles in determining the structure of the TBZ molecule and its conformational preferences were characterized. The UV-visible and infrared spectra of the isolated molecule (most stable trans conformer) were also calculated, and their assignment undertaken. The information obtained for the isolated molecule provided a strong basis for the understanding of the intermolecular interactions and properties of the crystalline compound. In particular, the infrared spectrum for the isolated molecule was compared with that of crystalline TBZ and the differences between the two spectra were interpreted in terms of the major intermolecular interactions existing in the solid state. The analysis of the infrared spectral data was complemented with vibrational results of up-to-date fully-periodic DFT calculations and Raman spectroscopic studies. The thermal behavior of TBZ was also investigated using differential scanning calorimetry (DSC) and thermogravimetry. Furthermore, a new TBZ–formic acid solvate [2-(1,3-thiazol-4-yl)benzimidazolium formate formic acid solvate] was synthesized and its crystal structure determined by X-ray diffraction. The Hirshfeld method was used to explore the intermolecular interactions in the crystal of the new TBZ solvate, comparing them with those present in the neat TBZ crystal. Raman spectroscopy and DSC studies were also carried out on the solvate to further characterize this species and investigate its temperature-induced desolvation.

2,2′-(2-Oxopropane-1,3-diyl)bis-(2-hydroxy-1H-indene-1,3(2H)-dione): synthesis, crystal, electronic and molecular docking studies

We have synthesized here a novel ninhydrin derivative 2,2′-(2-oxopropane-1,3-diyl)bis-(2-hydroxy-1H-indene-1,3(2H)-dione) (1) through a green and facile strategy with the use of acetic acid as catalyst. The structure has been determined by spectral analysis and by single crystal X-ray analysis. This molecule contains two 2-hydroxy-1,3-indanedione moieties fused with 2-oxo-propane at 1 and 3 positions. The molecular structure of the title compound (C21H14O7) has been optimized and the structural parameters have been calculated by DFT/B3LYP method using 6-311++G(d,p) basis set. The fundamental vibrational wave numbers and their intensities were calculated and a good agreement between observed FT-IR spectrum and scaled calculated wavenumbers has been achieved. The electronic properties of the molecule are discussed with the help of the descriptors such as HOMO–LUMO and MEPS. In addition, the molecular docking and NBO analyses are also carried out to get a better insight of the molecule. The major intermolecular interactions in the crystal structure are established through hydroxy group to carbonyl oxygen of the adjacent molecules by means of strong O–H…O hydrogen bonds leading to form a zigzag arrangement running along b-axis.

Structural study of three heteroaryl oximes, heteroaryl-N=OH: Compounds forming strong C3 molecular chains

In order to further investigate the structural chemistry of oximes and to further establish the main structural arrangements adopted, we have determined the crystal structure of and carried out Hirshfeld surface calculations on three heteroaryl oximes, namely (Z)-thiophene-2-carbaldehyde oxime (1), (Z)-1H-pyrrole-2 carbaldehyde oxime (2) and (Z)-5-nitrofuran-2-carbaldehyde oxime (3). As confirmed by both techniques, the major intermolecular interactions in each compound are classical N—H···O hydrogen bonds, which link the molecules into C3 chains. Such an arrangement has been previous reported as an important aggregation mode for oximes. Secondary interactions, C—H···π and C—H···O interactions, in compounds 1 and 2, and interactions involving the nitro group oxygen atoms in compound 3 link the chains into three dimensional arrays.

Crystal Structures of Two (3S,4aS, 8aS)-N-(1,1-dimethyl)decahydro-2-[(2R,3S)-2-hydroxy-arylsulfonyl]amino]-4-phenylbutyl]-3-isoquinolinecarboxamide. Hemihydrates: Compounds with Moderate Activity as Aspartyl Protease Inhibitors

The crystal structures of two hemihydrates of (3S,4aS, 8aS)-N-(1,1-dimethyl)decahydro-2-[(2R,3S)-2-hydroxy-3-[[arylsulfonyl]amino]-4-phenylbutyl]-3-isoquinolinecarboxamides [aryl = 4-nitrophenyl: [(1:X = 4-O 2 N) 2 ·H 2 O]; and aryl = 4-bromophenyl: [(1:X = 4-Br) 2 ·H 2 O] are reported. The chiral anhydrous compounds, prepared from (2S,3S)-Boc-phenylalanine epoxide, have been reported to exhibit moderate antimalarial activity in vitro against Plasmodium falciparum. The molecular conformations and major intermolecular interactions of the two hydrates are similar, despite there being two independent, albeit similar, molecules in [(1:X = Br) 2 ·H 2 O] compared to only one in [(1:X = 4-O 2 N) 2 ·H 2 O]. A common feature of both structures is that each water molecule is linked to four molecules of 1 via classical hydrogen bonds to form [[(1:X)4(H2O)] units, (X = 4-O2N or 4-Br). As a consequence of the water molecules in [(1:X = 4-O 2 N) 2 ·H 2 O] being in special positions and the slight differences between molecules, A and B, in [(1:X = 4-Br) 2 ·H 2 O], the former has as a symmetrical struture. Emanating from each water molecule in both structures are four chains of alternating molecules of water and 1: these are linked into three dimensional arrays. Compound [(1:X = 4-O 2 N) 2 H 2 O] crystallizes in the monoclinic space group C2 with a = 21.1431(9), b = 10.4886(6), c = 15.4597(9) A, b = 111.145(3)°and Z = 4. Compound [(1:X = 4-O 2 N) 2 H 2 O] crystallizes in the monoclinic space group P21 with a = 11.0860(9), b = 28.559(2), c = 11.5220(10) A, b = 117.585(3)° and Z = 4. A feature of both structures is that each water molecule is linked to four molecules of the sulfonamide via classical hydrogen bonds.

Crystal structures of (E)-2-(2-benzylidenehydrazinyl)quinoxalines: persistent N–H···N intermolecular hydrogen bonds but variable π···π interactions

Abstract The crystal structures of two (E)-2-(2-benzylidenehydrazin-1-yl)quinoxaline derivatives, (E)-2-(XYC6 H3-CH=N-NH)-quinoxalines, 1, namely (1: X=H; Y=4-MeO or 4-O2 N) have been determined. In both cases, the major intermolecular interactions are N–H···N(pyrazine) hydrogen bonds. While in both compounds π···π intermolecular stacking interactions are present, these involve different aromatic rings in each case and hence different structural motifs are formed. These findings – of persistent and dominant N–H···N(pyrazine) hydrogen bonds and variable π···π interactions – concur with the previous findings for other compounds 1. The substituents, Y, in (1: X=H; Y=4-MeO or 4-O2 N) play minor roles in the overall supramolecular arrangements.

A Donor–Acceptor–Donor Structured Organic Conductor with S···S Chalcogen Bonding

A novel thiophene derivative 7,9-di(thiophen-2-yl)-8H-cyclopenta[a]acenaphthylen-8-one (DTCPA) is shown to exhibit high electrical conductivity (1.97 × 10–2 ± 0.0018 S/cm at RT) in the crystalline state. The material shows two orders of increase in conductivity from normal solid to single crystalline state. The crystal structure has S···S chalcogen bonding, C–H···O hydrogen bonding, and π···π stacking as the major intermolecular interactions. The nature and strength of the S···S interactions in this structure have been evaluated by theoretical charge density analysis, and its contribution to the crystal packing quantified by Hirshfeld surface analysis. Further, thermal and morphological characterizations have been carried out, and the second harmonic generation (SHG) efficiency has been measured using the Kurtz–Perry method.

Nickel(ii), copper(ii) and zinc(ii) metallo-intercalators: structural details of the DNA-binding by a combined experimental and computational investigation

We present a thorough characterization of the interaction of novel nickel(II) (1), copper(II) (2) and zinc(II) (3) Schiff base complexes with native calf thymus DNA (ct-DNA), in buffered aqueous solution at pH 7.5. UV-vis absorption, circular dichroism (CD) and viscometry titrations provided clear evidence of the intercalative mechanism of the three square-planar metal complexes, allowing us to determine the intrinsic DNA-binding constants (K(b)), equal to 1.3 × 10(7), 2.9 × 10(6), and 6.2 × 10(5) M(-1) for 1, 2 and 3, respectively. Preferential affinity, of one order of magnitude, toward AT compared to GC base pair sequences was detected by UV-vis absorption titrations of 1 with [poly(dG-dC)]2 and [poly(dA-dT)]2. Structural details of the intercalation site of the three metal complexes within [dodeca(dA-dT)]2 were obtained by molecular dynamics (MD) simulations followed by density functional theory/molecular mechanics (DFT/MM) calculations. The calculations revealed that three major intermolecular interactions contribute to the strong affinity between DNA and the three metal complexes: (1) the electrostatic attraction between the two positively charged triethylammoniummethyl groups of the metal complexes and the negatively charged phosphate groups of the DNA backbone; (2) the intercalation of the naphthalene moiety within the four nitrogen bases of the intercalation site; (3) the metal coordination by exocyclic donor atoms of the bases, specifically the carbonyl oxygen and amine nitrogen atoms. Remarkably, the Gibbs formation free energy calculated for the intercalation complexes of 1, 2 and 3 with [dodeca(dA-dT)]2 in the implicit water solution is in agreement with the experimental Gibbs free energy values obtained from the DNA-binding constants as ΔG° = -RT ln(K(b)). In particular, the DNA-binding affinity trend, 1 > 2 > 3, is reproduced. Finally, the first shell coordination distances calculated for the intercalation complex 3/[dodeca(dA-dT)]2 are in excellent agreement with the experimental distances extracted from the extended X-ray absorption fine structure (EXAFS) spectrum of the corresponding 3/ct-DNA solutions. The latter results provided the first evidence of metal ion coordination by native DNA in aqueous solution.

Variation in supramolecular arrangements of hydrazones, o-H2NC6H4CMe[dbnd]NNHC6H4X (X[dbnd]H, o-, m- and p-NO2), derived from o-aminoacetophenone and phenylhydrazines

The crystal structures of four hydrazones, 1, derived from phenylhydrazines, XC6H4NHNH2 (XH, o-NO2, m-NO2 or p-NO2) with 2-aminoacetophenone are reported, as is the mono hydrochloride, (2: Xm-NO2), of (1: Xm-NO2). Consistent strong intramolecular hydrogen bonds in 1 are of the type, NH(amino)⋯N(hydrazono), while (1: Xm-NO2) portrays an additional NH(hydrazono)⋯O(nitro), intramolecular hydrogen bond. Of interest, different sets of strong intermolecular interactions are found even among the nitro derivatives, 1. In (1: Xo-NO2), the strongest intermolecular interactions are NH(amino)⋯O(nitro) hydrogen bonds, while in (1: Xm-NO2 and p-NO2), both NH(hydrazono)⋯O(nitro) and NH(amino)⋯N(amino) are present. These strong intermolecular hydrogen bonds coupled with different combinations of some of CH⋯O, ππ stacking interactions and NO⋯π generate different supramolecular arrays for (1: X=nitro): 2-D, 2-D and 3-D, respectively for (1: Xo-NO2), for (1: Xm-NO2) and (1: Xp-NO2). In (1: XH), the major intermolecular interactions are NH(hydrazono)⋯N(amino hydrogen bonds: these, supplemented by weaker NH⋯π and CH⋯π interactions, generate a two-dimensional array.While significant changes in the intermolecular interactions result on formation of the salt, (2: Xm-NO2) from (1: Xm-NO2), the strong NH(amino)⋯N(hydrazono) intramolecular hydrogen bonds persist. Strong intermolecular hydrogen bonds found in (2: Xm-NO2) are of the types NH⋯Cl (both hydrazone and amine), NH(amino)⋯O(nitro): these coupled with weaker CH⋯O, NO⋯π, and ππ generate a three dimensional array.

Hydrazones, ArNHN=CRCH2COX, from Reactions of Arylhydrazines, ArNHNH2, with 1,3-Dicarbonyl Compounds, RCOCH2COX(X = OR1 or NHPh): Crystal Structures of (E)-4-O2NC6H4NHN=CMeCH2CO2R1 (R1 = Me or Et) and (E)-PhNHN=CPhCH2CONHPh

The molecular and crystal structures of (E)-4-O2NC6H4NHN=CMeCH2CO2R1 (4: R1 = Me; 5: R1 = Et) and (E)-PhNHN=CPhCH2CONHPh (6) are reported from data collected at 120(2) K. The major intermolecular interactions in both 4 and 5 involve the hydazonyl NH and the carbonyl oxygen, with formation of symmetric dimers. Due to 4 and 5 each having different sets of additional intermolecular interactions, different supramolecular arrays are produced: molecules of 4 are linked into a three-dimension structure, while zig-zag chains of molecules of 5 are obtained. Chains of molecules of 6, prepared from PhNHNH2 and PhCOCH2CONHPh, are obtained from intermolecular hydrogen bonds involving amido NH and carbonyl oxygen moieties. Further interactions, C–H–π(arene), C–H–O and π–π stacking interactions in 6 produces a three dimensional array. Compound 4 crystallizes in the triclinic space group P − 1 with a = 7.7027(2) Ǻ, b = 7.8103(2) Ǻ, c = 11.1761(3) Ǻ, α = 77.054(2)°, β = 79.425(2)°, γ = 81.097(2)°. Compound 5 crystallizes in the triclinic space group P − 1 with a = 5.6323(2)Ǻ, b = 9.9695(3)Ǻ, c = 11.0286(4)Ǻ, α = 91.859(2)°, β = 102.034(2)°, γ = 98.898(3)°. Compound 6 crystallizes in the monoclinic space group P21/c with a = 10.4255(8)Ǻ, b = 10.4255(8)Ǻ, c = 9.3368(5)Ǻ, β = 113.780(4) °. Controlled reactions of arylhydrazines, ArNHNH2 with RCOCH2COX (X = OR or NHPh) produce ArNHN=CRCH2COX. The molecular and crystal structures of three such non-cyclised products are reported. While the major intermolecular interactions in each case involve the hydazonyl NH and the carbonyl oxygen, different three dimensional supramolecular arrangements are found.

Crystal structure of an electron-transfer complex between methylamine dehydrogenase and amicyanin.

The crystal structure of the complex between the quinoprotein methylamine dehydrogenase (MADH) and the type I blue copper protein amicyanin, both from Paracoccus denitrificans, has been determined at 2.5-A resolution using molecular replacement. The search model was MADH from Thiobacillus versutus. The amicyanin could be located in an averaged electron density difference map and the model improved by refinement and model building procedures. Nine beta-strands are observed within the amicyanin molecule. The copper atom is located between three antiparallel strands and is about 2.5 A below the protein surface. The major intermolecular interactions occur between amicyanin and the light subunit of MADH where the interface is largely hydrophobic. The copper atom of amicyanin and the redox cofactor of MADH are about 9.4 A apart. One of the copper ligands, His 95, lies between the two redox centers and may facilitate electron transfer between them.

Stabilities of leucine zipper dimers estimated by an empirical free energy method

The leucine zipper motif is a characteristic amino acid sequence found in dimeric DNA-binding proteins. Computer-generated models for leucine zippers were constructed as alpha-helical coiled dimers with leucine repeated every seventh residue. An empirical Gibbs free energy, delta G, function which incorporates hydrophobic force, electrostatic interactions, and conformational entropy loss as the major intermolecular interactions was used to estimate the delta G of dimer formation in fos, jun, and GCN4 zipper sequences. The calculations showed that complexes known to form stable homo- or heterodimers have favorable (negative) delta G, while other less stable complexes have unfavorable (positive) delta G. Leucines in position d of the coiled coil contribute large hydrophobic stabilization energies while residues in the a position contribute less to dimer stability. Hydrophobic contributions show little sequence specificity, however, and do not contribute significantly to homo/heterodimer preference. Charged residues in the e and g positions, on the other hand, determine homo/heterodimer specificity. In GCN4 homodimers, residues GLU el, Glu b2, Lys g2, and Lys e4 greatly contribute to dimer stability. The preferential stability of fos-jun heterodimer over the jun-jun and fos-fos homodimers is primarily due to the side chains Asp b1, Glu g1, Asp b2, Glu e2, Glu g2, Glu g3, and Lys a5 of the fos helix, and Arg c1, Lys g1, Lys b2, Lys e2, Arg e4, and Glu g4 of the jun helix.