Three leflunomide metabolite analogs

The title compounds, 1‐cyano‐2‐hydroxy‐N‐[4‐(methylsulfon­yl)phenyl]but‐2‐en­amide, C₁₂H₁₂N₂O₄S, PHI492, 1‐cyano‐2‐hydroxy‐N‐[3‐(methyl­sulfonyl)­phenyl]­but‐2‐en­amide, C₁₂H₁₂­N₂O₄S, PHI493, and N‐[3‐bromo‐4‐(trifluoro­methoxy)­phenyl]‐1‐cyano‐2‐hydroxybut‐2‐en­amide, C₁₂H₈Br­F₃N₂O₃, PHI495, are potent inhibitors of Bruton's tyrosine kinase (BTK). The molecular structures of these compounds are similar and they display similar hydrogen‐bonding networks and crystal packing. Examination of the crystal‐packing interaction in the three compounds reveals an alternating direction of adjacent mol­ecules in the crystalline lattice due to intermolecular cyano–amide hydrogen bonding. PHI492, a positional isomer of PHI493, does not form intermolecular O—H?O hydrogen bonds between mol­ecules and crystallizes in a space group different from that of PHI493 and PHI495. The aromatic ring and the amide group of each mol­ecule form a conjugated π‐system which ensures planarity, with further stabilization gained from intramolecular O—H?O hydrogen bonds.     

2‐Acetamido‐N‐benz­yl‐2‐(methoxy­amino)acetamides: functionalized amino acid anticonvulsants

In the crystal structure of 2‐acetamido‐N‐benz­yl‐2‐(methoxy­amino)acetamide (3L), C₁₂H₁₇N₃O₃, the 2‐acetyl­amino­acetamide moiety has a linearly extended conformation, with an inter­planar angle between the two amide groups of 157.3 (1)°. In 2‐acetamido‐N‐benz­yl‐2‐[meth­oxy(meth­yl)­amino]­acetamide (3N), C₁₃H₁₉N₃O₃, the planes of the two amide groups inter­sect at an angle of 126.4 (4)°, resulting in a chain that is slightly more bent. The replacement of the methoxy­amino H atom of 3L with a methyl group to form 3N and concomitant loss of hydrogen bonding results in some positional/thermal disorder in the meth­oxy­(methyl)­amino group. In both structures, in addition to classical N—H⋯O hydrogen bonds, there are also weak non‐standard C—H⋯O hydrogen bonds. The hydrogen bonds and packing inter­actions result in planar hydro­philic and hydro­phobic areas perpendicular to the c axis in 3L and parallel to the ab plane in the N‐meth­yl derivative. Stereochemical comparisons with phenytoin have identified two O atoms and a phenyl group as mol­ecular features likely to be responsible for the anticon­vulsant activities of these compounds.     

Tris­[2‐(benzoyl­amino)­ethyl]­amine

Tris­[2‐(benzoyl­amino)­ethyl]­amine [alternatively, N,N′,N′′‐(nitrilo­tri­ethyl)­tri­benz­amide], C₂₇H₃₀N₄O₃, adopts a folded structure, forming a symmetrical cavity with an average depth of 7.3 Å and width ranging from 4.1–4.4 Å. The folded structure is a result of one intramolecular N—H?O hydrogen bond. A linear chain motif along the c axis best describes the extended intermolecular N—H?O hydrogen bonding.     

C.I. Pigment Red 266

C.I. Pigment Red 266, or 4‐{[4‐(amino­carbonyl)­phenyl]­hydraz­ono}‐N‐(2‐methoxy­phenyl)‐3‐oxo‐3,4‐di­hydro­naph­tha­l­ene‐2‐carbox­amide, C₂₅H₂₀N₄O₄, adopts the keto–hydrazone tautomeric form with significant intramolecular hydrogen bonding. The mol­ecules pack to form layers involving an extensive network of intermolecular hydrogen bonds, in which the primary amide group plays a prominent role. The good technical performance of this pigment in application may be attributed principally to the pattern of intra‐ and intermolecular hydrogen bonding.     

Supramolecular structures of three isomeric 4‐(methyl­phenylamino)­pyridine‐3‐sulfonamides

The structures of the three title isomers, namely 4‐(2‐methyl­anilino)pyridine‐3‐sulfonamide, (I), 4‐(3‐methyl­anilino)pyridine‐3‐sulfonamide, (II), and 4‐(4‐methyl­anilino)pyridine‐3‐sulfonamide, (III), all C₁₂H₁₃N₃O₂S, differ in their hydrogen‐bonding arrangements. In all three mol­ecules, the conformation of the 4‐amino­pyridine‐3‐sulfon­amide moiety is conserved by an intra­molecular N—H⋯O hydrogen bond and a C—H⋯O inter­action. In the supra­mol­ecular structures of all three isomers, similar C(6) chains are formed via inter­molecular N—H⋯N hydrogen bonds. N—H⋯O hydrogen bonds lead to C(4) chains in (I), and to R₂²(8) centrosymmetric dimers in (II) and (III). In each isomer, the overall effect of all hydrogen bonds is to form layer structures.     

Novel heterocyclic inhibitors of matrix metalloproteinases: three 6H‐1,3,4‐thiadiazines

The title compounds, (2S)‐N‐[5‐(4‐chloro­phenyl)‐2,3‐di­hydro‐6H‐1,3,4‐thia­diazin‐2‐yl­idene]‐2‐[(phenyl­sulfonyl)­amino]­pro­pan­amide, C₁₈H₁₇ClN₄O₃S₂, (I), (2R)‐N‐[5‐(4‐fluoro­phenyl)‐6H‐1,3,4‐thia­diazin‐2‐yl]‐2‐[(phenyl­sulfonyl)amino]­propan­amide, C₁₈H₁₇FN₄O₃S₂, (II), and (2S)‐N‐[5‐(5‐chloro‐2‐thienyl)‐6H‐1,3,4‐thia­diazin‐2‐yl]‐2‐[(phenyl­sulfonyl)­amino]­propan­amide, C₁₆H₁₅ClN₄O₃S₃, (III), are potent inhibitors of matrix metalloproteinases. In all three compounds, the thia­diazine ring adopts a screw‐boat conformation. The mol­ecules of compound (I) show a short intramolecular N_Ala—H?N_exo hydrogen bond [N?N 2.661 (3) Å] and are linked into a chain along the c axis by N_endo—H?S_endo and N_endo—H?O_Ala hydrogen bonds [N?S 3.236 (3) and N?O 3.375 (3) Å] between neighbouring mol­ecules. In compound (II), the mol­ecules are connected antiparallel into a chain along the a axis by N_exo—H?O_Ala and N_Ala—H?N_endo hydrogen bonds [N?O 2.907 (6) and N?N 2.911 (6) Å]. The mol­ecules of compound (III) are dimerized antiparallel through N_exo—H?N_endo hydrogen bonds [N?N 2.956 (7) and 2.983 (7) Å]. The different hydrogen‐bonding patterns can be explained by an amido–imino tautomerism (prototropic shift) shown by different bond lengths within the 6H‐1,3,4‐thia­diazine moiety.     

The tetrapeptide Z‐Leu‐Aib‐Pro‐Val‐OBg monohydrate

The intramolecular hydrogen‐bonding pattern of Z‐Leu‐Aib‐Pro‐Val‐OBg monohydrate [(N‐benzhydryl­amino)­carbonyl­methyl N‐benzyl­oxy­carbonyl‐α‐amino­isobutyryl­prolyl­valinate monohydrate], C₄₃H₅₅N₅O₈·H₂O, is unusual for a tetrapeptide because, in addition to a 14 hydrogen bond, a second hydrogen bond of the type 15 is formed. This folding reflects the intramolecular hydrogen‐bonding pattern that this amino acid sequence adopts in the naturally occurring peptaibol alamethicin.     

Chlor­amine‐B sesquihydrate

In the title compound, sodium N‐chloro­benzene­sulfon­amide sesquihydrate, Na⁺·C₆H₅ClNO₂S^?·1.5H₂O, the sodium ion exhibits octahedral coordination by O atoms from three water mol­ecules and by three sulfonyl O atoms of three different N‐­chloro­benzene­sulfon­amide anions. A two‐dimensional polymeric layer consists of units, each comprising two face‐sharing octahedra which share four corners with four other such units, the layer running parallel to the ab plane. The water mol­ecules participate in hydrogen bonds of the types O—H?O, O—H?N and O—H?Cl.     

N‐{(1E)‐Amino­[3‐methyl‐5‐(4‐methyl­phenyl)‐4,5‐di­hydro‐1H‐pyrazol‐1‐yl]­methyl­ene}‐1H‐imidazole‐1‐carbox­amide

In the title compound, C₁₆H₁₈N₆O, an N‐carbonyl­imidazole derivative of pyrazoline‐1‐carboximid­amide, the π‐electron density of the N atom in the 1‐position on the pyrazoline ring is delocalized through the amidine moiety and the adjacent carbonyl group. The imidazole ring, though coplanar with the rest of the mol­ecule, is deconjugated. The pyrazoline ring adopts a flat‐envelope conformation, having the substituted phenyl ring oriented perpendicular to the mean plane of the heterocycle. Both of the two potential hydrogen‐bond donors are involved in intramolecular hydrogen‐bonding interactions.     

[2,6‐Bis(1H‐benzimidazol‐2‐yl‐κN3)­pyridine‐κN](di­methyl­form­amide‐κO)­(thio­sulfato‐κ2O,S)­nickel(II) mono­hydrate

The structure of the title compound, [Ni(ths)(bbip)(dmf)]·­H₂O [ths is thio­sulfate, S₂O₃; bbip is 2,6‐bis(1H‐benz­imidazol‐2‐yl)­pyridine, C₂₁H₁₃N₅; and dmf is di­methyl­form­amide, C₃H₇NO], is monomeric, with the nickel ion octahe­drally surrounded by an N,N′,N′′‐tridentate bbip mol­ecule, an S,O‐bidentate ths mol­ecule and an O‐monodentate dmf mol­ecule. The H atoms of the hydration water mol­ecule and the amino groups of bbip are involved in hydrogen bonding and determine a spatial organization of broad layers parallel to (001), which are connected by weak interactions.     

Piv‐Proψ[CH2–NH–O]Gly–NHiPr

The pseudodipeptide, (S)‐N‐iso­propyl {[N‐(pivaloyl)­pyrrol­idin‐2‐yl]­methyl­amino­oxy}acet­amide, C₁₅H₂₉N₃O₃, adopts a global extended conformation with the hydroxy­l­amine group in the g⁺/g^? structure. The C‐terminal amide NH interacts intramolecularly with the hydroxy­lamine O atom. Both NH bonds of each mol­ecule are hydrogen bonded to the C‐­terminal amide carbonyl of a neighbouring mol­ecule.     

A one‐dimensional copper coordination polymer containing both dicyan­amide and 1,10‐phenanthroline ligands

The crystal structure of catena‐poly­[[[acetato(1,10‐phenanthroline‐κ²N,N′)copper(II)]‐μ‐dicyan­amido‐κ²N¹:N⁵] trihydrate], {[Cu(C₂H₃O₂)(C₂N₃)(C₁₂H₈N₂)]·3H₂O}_n, consists of a zigzag chain formed by the polymer [Cu(CH₃COO)(dca)(phen)]_n (phen is 1,10‐phenanthroline and dca is dicyan­amide), with three water mol­ecules per repeat unit of the polymer. The Cu^II atom has a slightly distorted square‐pyramidal coordination environment consisting of two N atoms of the phen ligand, two nitrile N atoms of different dca ligands, one of them axial, and one O atom of the acetate anion. The compound forms a one‐dimensional chain using dca as an end‐to‐end bridging ligand. Non‐covalent interactions, π–π stacking and hydrogen bonding mediate the bundling of the polymer chains into a three‐dimensional structure, with the water mol­ecules playing an important role in the hydrogen bonding.     

Self‐assembly of 2‐pivaloyl‐6‐chloro­pterin

In the title compound, N‐(6‐chloro‐4‐oxo‐3,4‐di­hydro­pteridin‐2‐yl)­‐2,2‐di­methyl­propan­amide, C₁₁H₁₂ClN₅O₂, the rings in the pterin moiety are planar. The amide carbonyl O atom is in syn‐periplanar conformation while the C—N—C—C propanamide linkage is antiperiplanar. The N—H?N and N—H?O intermolecular hydrogen bonds transform the mol­ecules into infinite chains.     

A complex containing both five‐ and six‐coordinate [bis(5‐bromosalicyli­dene)benzene‐1,2‐diimine]chloro­iron(III)

The title compound, aqua­chloro{4,4′‐di­bromo‐2,2′‐[o‐phenylenebis­(nitrilo­methyl­idyne)]­diphenolato‐O,N,N′,O′}iron(III)–chloro{4,4′‐di­bromo‐2,2′‐[o‐phenyl­enebis­(nitrilomethyli‐dyne)]diphenolato‐O,N,N′,O′}iron(III)–di­methyl­form­amide (1/1/1), [FeCl(C₂₀H₁₂Br₂N₂O₂)][FeCl(C₂₀H₁₂Br₂N₂O₂)(H₂O)]·C₃H₇NO, contains one independent five‐coordinate [FeCl(C₂₀H₁₂Br₂N₂O₂)] monomer, one six‐coordinate [FeCl(C₂₀H₁₂Br₂N₂O₂)(H₂O)] monomer and a non‐coordinating di­methyl­form­amide solvent mol­ecule in the asymmetric unit. In the five‐coordinate monomer, the Fe atom shows distorted square‐pyramidal geometry, with the N and O atoms of the ligand at the base and the Cl atom at the apex of the pyramid. In the six‐coordinate monomer, the Fe atom is in a distorted octahedral geometry and coordinated by the donor atoms of the tetrafunctional ligand in the horizontal plane, and the coordination sphere is completed by the O atom of the water mol­ecule and the Cl atom at the axial positions. The title compound contains intermolecular O—H?O hydrogen bonds. Apart from these hydrogen bonds, there are also intermolecular C—H?Cl and C—H?O contacts.     

An analytic potential energy function for the amide–amide and amide–water intermolecular hydrogen bonds in peptides

An analytic potential energy function is proposed and applied to evaluate the amide–amide and amide–water hydrogen‐bonding interaction energies in peptides. The parameters in the analytic function are derived from fitting to the potential energy curves of 10 hydrogen‐bonded training dimers. The analytic potential energy function is then employed to calculate the N? H…O?C, C? H…O?C, N? H…OH₂, and C?O…HOH hydrogen‐bonding interaction energies in amide–amide and amide–water dimers containing N‐methylacetamide, acetamide, glycine dipeptide, alanine dipeptide, N‐methylformamide, N‐methylpropanamide, N‐ethylacetamide and/or water molecules. The potential energy curves of these systems are therefore obtained, including the equilibrium hydrogen bond distances R(O…H) and the hydrogen‐bonding energies. The function is also applied to calculate the binding energies in models of β‐sheets. The calculation results show that the potential energy curves obtained from the analytic function are in good agreement with those obtained from MP2/6‐31+G** calculations by including the BSSE correction, which demonstrate that the analytic function proposed in this work can be used to predict the hydrogen‐bonding interaction energies in peptides quickly and accurately. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009     

(Aceto­nitrile)­[2,6‐bis­(pyrazol‐1‐yl)­pyridine](isonicotin­amide)copper(II)–tetra­fluoro­borate–aceto­nitrile (1/2/2)

Molecules of the title compound, [Cu(C₂H₃N)(C₁₁H₉N₅)(C₆H₆N₂O)](BF₄)₂·2C₂H₃N, comprise (aceto­nitrile)[2,6‐bis(pyrazol‐1‐yl)­pyridine](isonicotin­amide)copper(II) cations, tetra­fluoro­borate anions and lattice aceto­nitrile mol­ecules. The cations have distorted square‐pyramidal geometries in which the N₃‐donor, viz. 2,6‐bis­(pyrazol‐1‐yl)­pyridine, and the N‐donor, viz. the isonicotin­amide ligand, occupy the four basal positions, with the coordinated aceto­nitrile N‐donor atom occupying the apical position. Pairs of cations are linked by N—H?F hydrogen bonds through tetra­fluoro­borate anions, forming centrosymmetric dimers, which are further linked by C—H?O hydrogen bonds into two‐dimensional undulating sheets, three of which interpenetrate to generate a two‐dimensional network.     

Packing effects in 4,4′‐bis(4‐hydroxy­butyl)‐2,2′‐bi­pyridine and 4,4′‐bis(4‐bromo­butyl)‐2,2′‐bi­pyridine

Structure analyses of 4,4′‐bis(4‐hydroxy­butyl)‐2,2′‐bi­pyridine, C₁₈H₂₄N₂O₂, (I), and 4,4′‐bis(4‐bromo­butyl)‐2,2′‐bi­pyridine, C₁₈H₂₂Br₂N₂, (II), reveal intermolecular hydrogen bonding in both compounds. For (I), O—H·N intermolecular hydrogen bonding leads to the formation of an infinite two‐dimensional polymer, and π stacking interactions are also observed. For (II), C—H·N intermolecular hydrogen bonding leads to the formation of a zigzag polymer. The two compounds crystallize in different crystal systems, but both mol­ecules possess C_i symmetry, with one half mol­ecule in the asymmetric unit.     

Dinicotinamidium squarate

The crystal structure determination of the dinicotinamidium squarate salt, 2C₆H₇N₂O⁺·C₄O₄²⁻, is reported, with the squarate dianion residing on an inversion centre and the unique cation in a general position. Salt formation occurs by donation of two H atoms from squaric acid to the nicotin­amide base. The crystal packing is derived from three types of hydrogen bonding. The primary hydrogen bond involves a squarate anion O atom and an H atom of the protonated pyridine group of the nicotin­amide, with an N⋯O distance of 2.5760 (13) Å. The second hydrogen bond involves a second anion O atom and an amide H atom, with an N⋯O distance of 2.8374 (14) Å. Thirdly, an intermolecular interaction between two coplanar nicotin­amide moieties occurs between an amide O atom and a symmetry‐related amide H atom, with an N1⋯O3 distance of 2.8911 (15) Å. These hydrogen bonds are also responsible for the planarity of the nicotin­amide moiety in the salt.     

Protonation products of pentaaminopentane as novel building blocks for hydrogen‐bonded networks

The structures of 3‐amino‐1,2R,4S,5‐tetra­ammoniopentane tetrachloride monohydrate, C₅H₂₁N₅⁴⁺·4Cl^?·H₂O, and 1,2R,3,4S,5‐penta­ammoniopentane tetra­chloro­zincate tri­chlor­ide monohydrate, (C₅H₂₂N₅)[ZnCl₄]Cl₃·H₂O, have been determined from single‐crystal X‐ray diffraction data. Both compounds show a complex network of N—H?O, O—H?Cl and N—H?Cl hydrogen bonds. There are a total of 14 H atoms of the tetra‐cation and 15 H atoms of the penta‐cation available for hydrogen bonding. However, due to the particular shape of the primary linear poly­ammonium cations, only a certain number of H atoms can be involved in hydrogen‐bond formation. It is further shown that hydrogen bonding has an influence on the conformation of such alkyl­ammonium cations.     

Two biologically active thio­phene‐3‐carbox­amide derivatives

The compounds 2‐{[(E)‐(4‐methoxy­phenyl)­methyl­ene]­amino}‐N‐(3‐methyl­phenyl)‐4,5,6,7‐tetra­hydro‐1‐benzo­thio­ph­ene‐3‐carbox­amide, C₂₄H₂₄N₂O₂S, (I), and N‐(4‐meth­yl­phenyl)‐2‐{[(E)‐(4‐methyl­phenyl)­methyl­ene]­amino}‐4,5,6,7‐tetra­hydro‐1‐benzo­thio­phene‐3‐carbox­amide, C₂₄H₂₄N₂OS, (II), show antibacterial and antifungal activities. The m‐toluidine ring in (I) and the p‐toluidine ring in (II) are coplanar with their respective thio­phene rings. In (I), an intermolecular C—H⋯O hydrogen bond is present, whereas (II) does not exhibit any significant intermolecular interactions. However, in both compounds, an intramolecular N—H⋯N hydrogen bond forms a pseudo‐six‐membered ring, thus locking the molecular conformation and eliminating conformational flexibility.