, the trimethoprim (TMP) molecule is protonated at one of the pyrimidine N atoms. The protonated N atom and 2-amine group of the TMP cation interact with the tetrafluoroborate anion through a pair of N—H F hydrogen bonds [graph set R 2 2 (8)]. The inversion-related TMP cations
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Non-covalent interactions, such as hydrogen bonding, halogen bonding and – interactions play major roles in molecular recognition and pharmaceutical drug design processes (Desiraju, 1989; Perumalla & Sun, 2014). N 6 -substituted adenine compounds continue to attract interest due to their biological activity as they can act as plant hormones and have anti-allergenic, antibacterial, antiviral and antifungal proper- ties (Hall, 1973; McHugh & Erxleben, 2011). N 6 -substituted adenine compounds also exhibit an extensive variety of hydrogen-bonding patterns and supramolecular architectures (Raghunathan & Pattabhi, 1981; Nirmalram et al., 2011; Tamilselvi & Muthiah, 2011; McHugh & Erxleben, 2011; Jennifer et al., 2014). The present investigation deals with the nitrate salt of N 9 -protonated benzoyladenine (I). Nitrate ions are known to play pivotal roles in hydrogen bonded supra- molecular architectures, as they have three oxygen atoms to act as good hydrogen bond acceptors (Murugesan et al., 1997; Cherouana et al., 2003; Balasubramani et al., 2005; Nirmalram et al., 2011).
Cinnamic acid derivatives are important building blocks in crystal engineering (Desiraju, 1989). Hydrogen bonding plays a key role in molecular recognition (Goswami & Ghosh, 1997) and crystal engineering research (Goswami et al., 1998). The design of a highly specific solid-state structure is of consider- able significance in organic chemistry due to important applications in the development of new optical, magnetic and electronic systems (Lehn, 1990). 2-Aminopyrimidine forms 1:1 adducts with different mono- and dicarboxylic acids (Etter & Adsmond, 1990) rather than individual self-assembly (Scheinbeim & Schempp, 1976). The adducts of carboxylic acids with 2-aminoheterocyclic ring systems form a graph-set motif of R 2
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the formation of supramolecular patterns (Fig. 2). The crystal structure is also stabilized by weak C—H F hydrogen bonds and – stacking interactions between 5FC A and B mol- ecules with an interplanar distance of 3.475 (6) A ˚ , centroid-to- centroid distance of 3.6875 (11) A ˚ , and slip angle of 19.52 . The crystal structure is further strengthened by a C—F interaction [3.4541 (14) A ˚ ] between 5-fluorocytosinium mol- ecule A and the melamine molecule (Fig. 3).
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molecule of N 6 -benzoyladenine (BA) and one molecule of 4-hydroxybenzoic acid (HBA). The N 6 -benzoyladenine (BA) has an N(7)—H tautomeric form with nonprotonated N-1 and N-3 atoms. This tautomeric form is stabilized by a typical intramolecular N—H O hydrogen bond between the carbonyl (C O) group and the N(7)—H hydrogen on the Hoogsteen face of the purine ring, forming a graph-set S(7) ring motif. The primary robust R 2 2 (8) ring motif is
Crystal engineering is defined as the rational design of crys- talline solids through control of intermolecular interactions (hydrogen bonding, hydrophobic forces, van der Waals forces, – interactions and electrostatic forces). New solid forms of pharmaceuticals are designed using the crystal engineering approach. These engineered solids have technological and legal importance. Among the intermolecular interactions, hydrogen bonding is the master key for molecular recognition in biological systems because of its strength and directionality (Almarsson & Zaworoko, 2004; Desiraju, 1995). It plays a dominant role in molecular aggregates (Samuel, 1997; Tutughamiarso & Egert, 2012) and three-dimensional struc- ture, stability and function of biomacromolecules (Gould, 1986). In particular, pyrimidine derivatives are used in the treatment of antiviral, antifungal, antitumor and cardiovas- cular diseases. 5-fluorocytosine (5FC) is a synthetic anti- mycotic compound, first synthesized in 1957 and widely used as an antitumor agent it is also active against fungal infection (Heidelberger et al., 1957; Portalone & Colapietro, 2007; Vermes et al., 2000). It becomes active by deamination of 5FC into 5-fluorouracil by the enzyme cytosine deaminase (CD) and inhibits RNA and DNA synthesis (Morschha¨user, 2003). Picric acid forms charge-transfer complexes with many organic compounds. It functions not only as an acceptor to form
, the asymmetric unit consists of an aminopyridinium cation and a p-nitro- benzoate anion, with proton transfer occurring to the aromatic N atom of the 2-aminopyridine molecule. In the crystal structure, the two ions are interconnected by N—H O hydrogen bonds.
loop of O—H O hydrogen bonds is formed between four water molecules and the two carboxylate groups to form a supramolecular chain along the a axis. Molecules A and B constitute a base pair via N—H N hydrogen bonds, and these base pairs are cross-linked by N—H O and C—H O hydrogen bonds.
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The three isomers of pyridinecarboxamide; 2-pyridine carboxamide or picolinamide, 3-pyridinecarboxamide or nicotinamide and 4-pyridinecarboxamide or isonicotina- mide are a class of medicinal agents which can be classi- fied as GRAS (generally regarded as safe) compounds. In particular, nicotinamide (niacinamide, Vitamin B3) and picolinamide show important biological activity with a coenzyme called NAD (nicotinamide adenine dinucleo- tide), which plays important roles in more than 200 amino acid and carbohydrate metabolic reactions . In general pyridinecarboxamides are excellent co-crystal- lizing compound. The amide group has two hydrogen bond donors and two lone pairs on the carbonyl O atom. A second hydrogen bond acceptor is the lone pair on the N atom of the pyridine ring. This makes these molecules very versatile for a variety of hydrogen bonded interac- tions, especially in pharmaceutical co-crystals [2-13]. The molecular structures and vibrational spectra of the three isomers has been the subject of recent theoretical studies [14,15], and from the crystal structure point of view, all isomer compounds exhibit polymorphism . Nicotinamide has four polymorphs, the most stable crys- tallize in a monoclinic form , Isonicotinamide has three polymorphs in monoclinic and orthorhombic forms , and Picolinamide exists under two polymorphic structures . The polymorph form with crystal struc- ture in the Crystal Structure Database , was reported using Weissenberg photographic data and R = 0.127 .
crystallizes as centrosymmetric mononuclear molecules with octahedrally coordinated zinc, all pairs of equivalent ligands being mutually trans . Intramolecular hydrogen bonding links each aqua ligand with an uncoordinated carboxylate O atom, and intermolecular hydrogen bonding between aqua ligands and the carbonyl O atoms of N,N-diethylnicotinamide ligands link the molecules together into chains.
Compared with the packing arrangement in (I) (Hanson et al., 2006), a more complicated structural configuration occurs in the dimethyl analogue, (II). This compound is assembled as a head-to-tail dimer, exhibiting both intramolecular hydrogen bonding (C2B N2B and N2A C2A) and intermolecular hydrogen bonding with the carbonyl O atom (atom O1B and the isoxazole H atom on atom C10A, and the H atom on the secondary amine atom N1A), producing a pocket between
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comprises inversion-related pairs of phenazinium ions linked by C—H N hydrogen bonds. The phenazinium N—H atoms are hydrogen bonded to the bisulfate anions. The bisulfate anions and water molecules are linked by O—H O hydrogen-bonding interactions into a structural ladder motif parallel to the a axis.
One of these usually ha» a «ouch lower energy them the other so that there its no splitting of £©ra and first vibrational levels and the fundamental frequency is single. There will he some vibrational level at which the energy of the M l * « »ft system becomes similar to the energy for the ground state for A***iUB, and if the symmetries of the levels are appropriate they will interact and produce a double energy level. Barrow deduces that if the value for the acid A-H, as determined in aqueeu» solution, is 5 units greater than the acid I W , then there will be a doubling of the fundamental frequency as observed in non~;>olar solvents. If th© values differ by 15 units then splitting will occur in the second vibrational level and though the fundamental vibrational transition is single, th© first overtone will be doubled. If the suggestion of Harrow is applicable to this case, the doubling of v^(0— 2) would provide definite evidence for a hydrogen bond in the
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Polyoxygenated steroids possessing a wide range of oxygenation and nuclear substitution patterns have been isolated from a variety of marine organisms. Some of them show antitumour and antinflammatory activities as well as other biological effects. Thus, the research in this field is still very active. Previous studies in our group focused on the isolation of polyoxygenated steroids from marine sources (Piccialli & Sica, 1986, 1987; Notaro et al., 1991) as well as on the synthesis (Madaio, Piccialli & Sica, 1988; Migliuolo et al., 1992) of some of them exploiting new ruthenium tetroxide oxygenation protocols developed in our laboratories (Piccialli et al., 2013; Notaro et al., 1994). As a continuation of our interest in this field, we have now undertaken a study aimed at preparing a new collection of polyoxygenated steroids for structure-activity relationship studies and in particular at the synthesis of new 9,11-secosteroids. Many representatives of this sub-class of steroids have been shown to possess in vitro cytotoxic activity against various human cancer cell lines (Chen et al., 2011). Due to its functionalization pattern, the title compound, shown in the Scheme, is a good starting product to further oxygenate the steroid nucleus at C and D rings, as well as to obtain the 9,11-secosteroid motif. For now, the title compound has been synthesized starting from commercially available 7-dehydrocholesteryl acetate (Fig. 1).
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The findings of this study showed that 7 SNPs were damaged by using SIFT (A288S, M731T, R172C, R50Q, G460W, K197N, G75V) and 4 (A288S, M731T, R172C, R50Q) out of the seven SNPs were deleterious by PROVEAN, while 4 SNPs were found to be disease caused by PHD-SNP (A288S, R172C) and 2 SNPS (A288S, M731T, R172C, G75V and G460W) by using SNPS & GO. Polyphen results showed that 4 SNPS (M731T, R50Q, G460W, K197N) were probably and possibly damaging, moreover Panther results indicated A288S, M731T and G460W were probably damaging. I-Mutant Suite results showed that 6 mutations were decreasing protein stability (A288S, M731T, R172C, R50Q, K197N, G75V) while G460W showed increased stability of protein. By comparing output of the 6 above mentioned in-cilico bioinformatics tools, A288S, M731T, R172C, G75V, G460W, R50Q and K197N mutations were found functionally significant. Using MutPred to determine the degree of tolerance of each amino acid substitution on the bases of physo-chemical properties, results of this study showed that, A288S,R50Q, K197N and G460W were harmful with loss of sheet P = 0.0228, 0.0115, 0.02 and 0.0549 respectively. Furthermore, these 7 SNPs were analysed by structurally and functionally by using 5 bioinformatics tools; Chimera, Mutation 3D, PDB, modeller and ELASPIC. In the present study the “core” re- sidues were found predominant within the mutations, this residues are defined as residues which are exposed in the monomeric protein but buried in the protein complex. Core residues are typically hydrophobic with a com- position strongly divergent from the composition of the remainder of the protein surface  Core residues supply the bulk of the energy driving association by hydrophobic interactions  The hydrophobic interactions within the complex cause the core region to become tightly packed upon complex association with little room for conformational variability. For these reasons, the core residues are strongly conserved during evolution  and mutations in this region are usually more strongly unfavorable when compared to mutations at the periphery of the interface. Results of Mutation3D server showed 3 of mutations (STEA4, PLD2, AZIN2, rs28933400, rs2286672, rs16835244 genes and corresponding rsSNPs respectively) were found to be with a high risk to hypertension. Hydrogen bonding and clashes of the mutations A288S, M731T, and R172C showed different numbers of hydrogen bonding between mutant residue and wild type, the differences of H-bonding between the wild and mutant residues may indicated a significant effect on protein stability, these results were obtained by using Chimera program 1.8.
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Compared to 4a, it can be seen that all of the new peptide analogs synthesized in this series (4b-4e) decrease β-hairpin stability overall. The most destabilizing substitution is that of azaVal 3 , followed by Gly 3 and azaGly 3 . Glycine has been reported as one of least tolerant amino acids to adopt β -sheet conformation due to its inherent flexibility and lack of side chain chemistry. 7 It is important to note, however, that the aza-glycine analog (4d) does have conformational restrictions as inferred by the diacylhydrazine computational (Figure 1.7, p. 12), as well as additional hydrogen-bonding opportunities. However, as can be seen here, this did not lead to increased β-hairpin stability relative to the glycine 3 analog (4e). In accordance with what was observed with peptide 3c, D -Val 3 substitution in peptide 4c was
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Abstract: Simulation and computational analysis of 6-gingerol and 6-shogaol is done to evaluate their binding affinity against ERα. Active site prediction was done using Computed Atlas of Surface Topography of Proteins (CASTp) to determine the binding pocket of ERα. Molecular docking and molecular dynamics (MD) simulation were done to assess the binding affinity and stability of the ligand-ERα complexes formed. Results showed that Tamoxifen have lowest binding energy (-9.61 ± 0.39 kcal/mol) followed by 6-gingerol (-6.59 ± 0.29 kcal/mol) and 6-shogaol (-5.70 ± 0.36 kcal/mol). Inhibition constant (Ki) range of TMX-ERα was found to be drastically lower than both 6GN-ERα and 6SG-ERα. Based on the difference in the binding energy range and inhibition constant, 6- gingerol and 6-shogaol showed less potential in substituting tamoxifen for the inhibition of ERɑ. Docking complexes formed was supported with stability in root mean square deviation (RMSD) and total binding energy of the complexes. The study is concluded that 6-gingerol have high level of interactions with the ERα active site in terms of hydrogen bonding whereas hydrophobic interactions are observed with both 6-gingerol and 6-shogaol. However, both ginger bioactive compounds poses low potential as substitute in comparison with tamoxifen against ERα.
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The carboxyl groups of the fumarate anion are coplanar with the carbon skeleton, the maximum atomic deviation from the mean plane defined by all atoms of the fumarate being 0.0806 (14) Å (O1). The fumarate anions link with DABT cations through classic hydrogen bonding between the carboxyl and amino groups and weak C—H···O hydrogen bonding between the carboxyl and thiazole ring, forming a three-dimensional supramolecular structure, as shown in Fig. 2. S2. Experimental
ion exhibits a tetrahedral coordination environment defined by two benzene-1,4-dicarboxylate dianions and two 4-pyridinealdoxime ligands. The dianions bridge the Zn II ions, giving a zigzag chain along the b axis. Adjacent chains are connected by O—H O hydrogen bonds, forming a cavity in which an uncoordinating 4-pyridine- aldoxime molecule is located; this molecule is linked by O— H O and O—H N hydrogen bonds to the zigzag chain.
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There are several types of hydrogen-bonding interactions present in 1, as seen in Table 3. The acetonitrile solvate participates as acceptor in C—H N hydrogen bonds in which an aromatic hydrogen atom (H9) is donor. Additionally, C— H O hydrogen bonds involving the uncoordinated acetate oxygen atom O2 as acceptor and the aromatic carbon atoms C10 and C16 as donors result in chains that run parallel to [1 10] (Fig. 4). In 2, the most significant hydrogen-bonding interactions (Table 4) involve the disordered ethanol solvate molecule, which participates as donor in O—H O hydrogen bonding with the uncoordinated acetate oxygen atoms O2 and O6 as acceptors.
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