Crystal structures of two new divalent transition-metal salts of carb-oxy-benzene-sulfonate anions.

Hexa-aqua-nickel(II) bis-(3-carb-oxy-4-hy-droxy-benzene-sulfonate) dihydrate, [Ni(H2O)6][C6H3(CO2H)(OH)SO3]2·2H2O, (I), crystallizes in the triclinic space group P with the nickel(II) aqua complexes on centers of inversion. The carboxyl-ate group is protonated and neither it nor the sulfonate group is involved in direct coordination to the metal ions. The structure consists of alternating layers of inorganic cations and organic anions linked by O-H⋯O hydrogen bonds that also include non-coordinated water mol-ecules of crystallization. The first-row divalent transition-metal salts of this anion are reported as both dihydrates and tetra-hydrates, with two distinct structures for the dihydrates that are both layered but differ in the hydrogen-bonding pattern. Compound (I) represents the second known example of one of these structures. Hexa-aqua-cobalt(II) bis-(3-carb-oxy-benzene-sulfonate) dihydrate, [Co(H2O)6][C6H4(CO2H)SO3]2·2H2O, (II), also crystallizes in triclinic P with the cobalt(II) aqua complexes on centers of inversion. The structure is also built of alternating layers of complex cations and organic anions without direct coordination to the metal by the protonated carboxyl-ate or unprotonated sulfonate groups. A robust O-H⋯O hydrogen-bonding network involving primarily the coordin-ated and non-coordinated water mol-ecules and sulfonate groups directs the packing. This is the first reported example of a divalent transition-metal salt of the 3-carb-oxy-benzene-sulfonate anion.

The low-temperature triclinic crystal structure of silver 3-sulfo-benzoic acid.

Poly[(µ4-3-carboxybenzenesulfonato)silver(I)], Ag(O3SC6H4CO2H) or [Ag(C7H5O5S)] n , has been found to undergo a reversible phase transition from monoclinic to triclinic between 160 and 150 K. The low-temperature triclinic structure (space group P ) has been determined at 100 K. In contrast to the reported room temperature monoclinic structure, in which the nearly equivalent carboxyl-ate C-O distances indicate that the acidic hydrogen is randomly distributed between the O atoms, at 100 K the C-O (protonated) and C=O (unprotonated) bonds are clearly resolved, resulting in the reduction in symmetry from C2/c to P .

Crystal structures of two coordination isomers of copper(II) 4-sulfo-benzoic acid hexa-hydrate and two mixed silver/potassium 4-sulfo-benzoic acid salts.

A reaction of copper(II) carbonate and potassium 4-sulfo-benzoic acid in water acidified with hydro-chloric acid yielded two crystalline products. Tetra-aqua-bis-(4-carb-oxy-benzene-sulfonato)-copper(II) dihydrate, [Cu(O3SC6H4CO2H)2(H2O)4]·2H2O, (I), crystallizes in the triclinic space group P with the Cu2+ ions located on centers of inversion. Each copper ion is coordinated to four water mol-ecules in a square plane with two sulfonate O atoms in the apical positions of a Jahn-Teller-distorted octa-hedron. The carboxyl-ate group is protonated and not involved in coordination to the metal ions. The complexes pack so as to create a layered structure with alternating inorganic and organic domains. The packing is reinforced by several O-H⋯O hydrogen bonds involving coordinated and non-coordinated water mol-ecules, the carb-oxy-lic acid group and the sulfonate group. Hexa-aqua-copper(II) 4-carb-oxy-benzene-sulfonate, [Cu(H2O)6](O3SC6H4CO2H)2, (II), also crystallizes in the triclinic space group P with Jahn-Teller-distorted octa-hedral copper(II) aqua complexes on the centers of inversion. As in (I), the carboxyl-ate group on the anion is protonated and the structure consists of alternating layers of inorganic cations and organic anions linked by O-H⋯O hydrogen bonds. A reaction of silver nitrate and potassium 4-sulfo-benzoic acid in water also resulted in two distinct products that have been structurally characterized. An anhydrous silver potassium 4-carb-oxy-benzene-sulfonate salt, [Ag0.69K0.31](O3SC6H4CO2H), (III), crystallizes in the monoclinic space group C2/c. There are two independent metal sites, one fully occupied by silver ions and the other showing a 62% K+/38% Ag+ (fixed) ratio, refined in two slightly different positions. The coordination environments of the metal ions are composed primarily of sulfonate O atoms, with some participation by the non-protonated carboxyl-ate O atoms in the disordered site. As in the copper compounds, the cations and anions cleanly segregate into alternating layers. A hydrated mixed silver potassium 4-carb-oxy-benzene-sulfonate salt dihydrate, [Ag0.20K0.80](O3SC6H4CO2H)·2H2O, (IV), crystallizes in the monoclinic space group P21/c with the Ag+ and K+ ions sharing one unique metal site coordinated by two water mol-ecules and six sulfonate O atoms. The packing in (IV) follows the dominant motif of alternating inorganic and organic layers. The protonated carboxyl-ate groups do not inter-act with the cations directly, but do participate in hydrogen bonds with the coordinated water mol-ecules. (IV) is isostructural with pure potassium 4-sulfo-benzoic acid dihydrate.

Models for potential dendritic nitric oxide donors: crystal structures of two 2-nitroanilino precursors and nitric oxide-release behavior of the nitrosated derivatives.

Two molecular precursors to dendrimeric materials that could serve as slow and sustained NO-releasing therapeutic agents have been synthesized and characterized. N1,N4-Bis(2-nitrophenyl)butane-1,4-diamine, C16H18N4O4, (I), crystallizes in a lattice with equal populations of two molecules of different conformations, both of which possess inversion symmetry through the central C-C bond. One molecule has exclusively anti conformations along the butyl chain, while the other has a gauche conformation of the substituents on the first C-C bond. N2,N2-Bis[2-(2-nitroanilino)ethyl]-N1-(2-nitrophenyl)ethane-1,2-diamine, C24H27N7O6, (II), crystallizes with one unique molecule in the asymmetric unit. Neighboring pairs of molecules are linked into dimers via N-H...O amine-nitro hydrogen bonds. The dimers are assembled into layers that stack in an A-B-A-B sequence such that the repeat distance in the stacking direction is over 46 Å. Molecular NO-release agents N1,N4-bis(2-nitrophenyl)-N1,N4-dinitrosobutane-1,4-diamine, C16H16N6O6, (III), and N1-(2-nitrophenyl)-N2,N2-bis{2-[(2-nitrophenyl)(nitroso)amino]ethyl}-N1-nitrosoethane-1,2-diamine, C24H24N10O9, (IV), were prepared via treatment of (I) and (II), respectively, with NaNO2 and acetic acid. The release of NO from solid-phase samples of (III) and (IV) suspended in phosphate buffer was monitored spectroscopically over a period of 21 days. Although (IV) released a greater amount of NO, as expected due to it having three NO moieties for every two in (III), the (IV):(III) ratio of the rate and extent of NO release was significantly less than 1.5:1, suggesting that some combination of electronic, chemical, and/or steric factors may be affecting the release process.

N-Benzylnicotinamide and N-benzyl-1,4-dihydronicotinamide: useful models for NAD+ and NADH.

3-Aminocarbonyl-1-benzylpyridinium bromide (N-benzylnicotinamide, BNA), C13H13N2O+·Br-, (I), and 1-benzyl-1,4-dihydropyridine-3-carboxamide (N-benzyl-1,4-dihydronicotinamide, rBNA), C13H14N2O, (II), are valuable model compounds used to study the enzymatic cofactors NAD(P)+ and NAD(P)H. BNA was crystallized successfully and its structure determined for the first time, while a low-temperature high-resolution structure of rBNA was obtained. Together, these structures provide the most detailed view of the reactive portions of NAD(P)+ and NAD(P)H. The amide group in BNA is rotated 8.4 (4)° out of the plane of the pyridine ring, while the two rings display a dihedral angle of 70.48 (17)°. In the rBNA structure, the dihydropyridine ring is essentially planar, indicating significant delocalization of the formal double bonds, and the amide group is coplanar with the ring [dihedral angle = 4.35 (9)°]. This rBNA conformation may lower the transition-state energy of an ene reaction between a substrate double bond and the dihydropyridine ring. The transition state would involve one atom of the double bond binding to the carbon ortho to both the ring N atom and the amide substituent of the dihydropyridine ring, while the other end of the double bond accepts an H atom from the methylene group para to the N atom.

Two N-(2-phenylethyl)nitroaniline derivatives as precursors for slow and sustained nitric oxide release agents.

Notwithstanding its simple structure, the chemistry of nitric oxide (NO) is complex. As a radical, NO is highly reactive. NO also has profound effects on the cardiovascular system. In order to regulate NO levels, direct therapeutic interventions include the development of numerous NO donors. Most of these donors release NO in a single high-concentration burst, which is deleterious. N-Nitrosated secondary amines release NO in a slow, sustained, and rate-tunable manner. Two new precursors to sustained NO-releasing materials have been characterized. N-[2-(3,4-Dimethoxyphenyl)ethyl]-2,4-dinitroaniline, C16H17N3O6, (I), crystallizes with one independent molecule in the asymmetric unit. The adjacent amine and nitro groups form an intramolecular N-H...O hydrogen bond. The anti conformation about the phenylethyl-to-aniline C-N bond leads to the planes of the arene and aniline rings being approximately perpendicular. Molecules are linked into dimers by weak intermolecular N-H...O hydrogen bonds such that each amine H atom participates in a three-center interaction with two nitro O atoms. The dimers pack so that the arene rings of adjacent molecules are not parallel and π-π interactions do not appear to be favored. N-(4-Methylsulfonyl-2-nitrophenyl)-L-phenylalanine, C16H16N2O6S, (II), with an optically active center, also crystallizes with one unique molecule in the asymmetric unit. The L enantiomer was established via the configuration of the starting material and was confirmed by refinement of the Flack parameter. As in (I), there is an intramolecular N-H...O hydrogen bond between adjacent amine and nitro groups. The conformation of the molecule is such that the arene rings display a dihedral angle of ca 60°. Unlike (I), molecules are not linked via intermolecular N-H...O hydrogen bonds. Rather, the carboxylic acid H atom forms a classic, approximately linear, O-H...O hydrogen bond with a sulfone O atom. Pairs of molecules related by twofold rotation axes are linked into dimers by two such interactions. The packing pattern features a zigzag arrangement of the arene rings without apparent π-π interactions. These structures are compared with reported analogues, revealing significant differences in molecular conformation, intermolecular interactions, and packing that result from modest changes in functional groups. The structures are discussed in terms of potential NO-release capability.

A series of N-(2-phenylethyl)nitroaniline derivatives as precursors for slow and sustained nitric oxide release agents.

2,4-Dinitro-N-(2-phenylethyl)aniline, C14H13N3O4, (I), crystallizes with one independent molecule in the asymmetric unit. The adjacent amine and nitro groups form an intramolecular N-H...O hydrogen bond. The anti conformation about the ethyl C-C bond leads to the phenyl and aniline rings being essentially parallel. Molecules are linked into dimers by intermolecular N-H...O hydrogen bonds, such that each amine H atom participates in a three-centre interaction with two nitro O atoms. Though the dimers pack so that the arene rings of adjacent molecules are parallel, the rings are staggered and π-π interactions do not appear to be favoured. 4,6-Dinitro-N,N'-bis(2-phenylethyl)benzene-1,3-diamine, C22H22N4O4, (II), differs from (I) in the presence of a second 2-phenylethylamine group on the substituted ring. Compound (II) also crystallizes with one unique molecule in the asymmetric unit. Both amine groups are involved in intramolecular N-H...O hydrogen bonds with adjacent nitro groups. Although one ethyl group adopts an anti conformation as in (I), the other is gauche, with the result that the pendant phenyl rings are not parallel. The amine group that is part of the gauche conformation participates in a three-centre N-H...O hydrogen bond with the nitro group of a neighbouring molecule, leading to dimers as in (I). The other amine H atom does not form any intermolecular hydrogen bonds. The packing leads to separations of ca 3.4 Šof the parallel anti phenyl and aminobenzene rings. 2-Cyano-4-nitro-N-(2-phenylethyl)aniline, C15H13N3O2, (III), differs from (I) only in having a cyano group in place of the 2-nitro group. The absence of the adjacent nitro group eliminates the intramolecular N-H...O hydrogen bond. Molecules of (III) adopt the same anti conformation about the ethyl group as in (I), but crystallize in the higher-symmetry monoclinic space group P21/n. The molecules are linked into dimers via N-H...N amine-cyano hydrogen bonds, while the nitro groups are not involved in any N-H...O interactions. Owing to the different symmetry, the molecules pack in a herringbone pattern with fewer face-to-face interactions between the rings. The closest such interactions are about 3.5 Šbetween rings that are largely slipped past one another. 4-Methylsulfonyl-2-nitro-N-(2-phenylethyl)aniline, C15H16N2O4S, (IV), differs from (I) in having a methylsulfonyl group in place of the 4-nitro group. The intramolecular N-H...O hydrogen bond is present as in (I). However, unlike (I), the conformation about the ethyl group is gauche, so the two arene rings are nearly perpendicular rather than parallel. The packing is significantly different from the other three structures in that there are no intermolecular hydrogen bonds involving the N-H groups. The molecules are arranged in tetragonal columns running along the c axis, with the aniline rings mostly parallel and separated by ca 3.7 Å. Taken together, these structures demonstrate that modest changes in functional groups cause significant differences in molecular conformation, intermolecular interactions and packing.

N,N'-diethyl-4-nitrobenzene-1,3-diamine, 2,6-bis(ethylamino)-3-nitrobenzonitrile and bis(4-ethylamino-3-nitrophenyl) sulfone.

N,N'-diethyl-4-nitrobenzene-1,3-diamine, C(10)H(15)N(3)O(2), (I), crystallizes with two independent molecules in the asymmetric unit, both of which are nearly planar. The molecules differ in the conformation of the ethylamine group trans to the nitro group. Both molecules contain intramolecular N-H...O hydrogen bonds between the adjacent amine and nitro groups and are linked into one-dimensional chains by intermolecular N-H...O hydrogen bonds. The chains are organized in layers parallel to (101) with separations of ca 3.4 A between adjacent sheets. The packing is quite different from what was observed in isomeric 1,3-bis(ethylamino)-2-nitrobenzene. 2,6-Bis(ethylamino)-3-nitrobenzonitrile, C(11)H(14)N(4)O(2), (II), differs from (I) only in the presence of the nitrile functionality between the two ethylamine groups. Compound (II) crystallizes with one unique molecule in the asymmetric unit. In contrast with (I), one of the ethylamine groups, which is disordered over two sites with occupancies of 0.75 and 0.25, is positioned so that the methyl group is directed out of the plane of the ring by approximately 85 degrees. This ethylamine group forms an intramolecular N-H...O hydrogen bond with the adjacent nitro group. The packing in (II) is very different from that in (I). Molecules of (II) are linked by both intermolecular amine-nitro N-H...O and amine-nitrile N-H...N hydrogen bonds into a two-dimensional network in the (10 2) plane. Alternating molecules are approximately orthogonal to one another, indicating that pi-pi interactions are not a significant factor in the packing. Bis(4-ethylamino-3-nitrophenyl) sulfone, C(16)H(18)N(4)O(6)S, (III), contains the same ortho nitro/ethylamine pairing as in (I), with the position para to the nitro group occupied by the sulfone instead of a second ethylamine group. Each 4-ethylamino-3-nitrobenzene moiety is nearly planar and contains the typical intramolecular N-H...O hydrogen bond. Due to the tetrahedral geometry about the S atom, the molecules of (III) adopt an overall V shape. There are no intermolecular amine-nitro hydrogen bonds. Rather, each amine H atom has a long (H...O ca 2.8 A) interaction with one of the sulfone O atoms. Molecules of (III) are thus linked by amine-sulfone N-H...O hydrogen bonds into zigzag double chains running along [001]. Taken together, these structures demonstrate that small changes in the functionalization of ethylamine-nitroarenes cause significant differences in the intermolecular interactions and packing.

4,6-Dinitro-N,N'-di-n-octylbenzene-1,3-diamine, 4,6-dinitro-N,N'-di-n-undecylbenzene-1,3-diamine and N,N'-bis(2,4-dinitrophenyl)octane-1,8-diamine.

4,6-Dinitro-N,N'-di-n-octylbenzene-1,3-diamine, C(22)H(38)N(4)O(4), (I), 4,6-dinitro-N,N'-di-n-undecylbenzene-1,3-diamine, C(28)H(50)N(4)O(4), (II), and N,N'-bis(2,4-dinitrophenyl)octane-1,8-diamine, C(20)H(24)N(6)O(8), (III), are the first synthetic meta-dinitroarenes functionalized with long-chain aliphatic amine groups to be structurally characterized. The intra- and intermolecular interactions in these model compounds provide information that can be used to help understand the physical properties of corresponding polymers with similar functionalities. Compounds (I) and (II) possess near-mirror symmetry, with the octyl and undecyl chains adopting fully extended anti conformations in the same direction with respect to the ring. Compound (III) rests on a center of inversion that occupies the mid-point of the central C-C bond of the octyl chain. The middle six C atoms of the chain form an anti arrangement, while the remaining two C atoms take hard turns almost perpendicular to the rest of the chain. All three molecules display intramolecular N-H...O hydrogen bonds between the amine and nitro groups, with the same NH group forming a bifurcated intermolecular hydrogen bond to the nitro O atom of an adjacent molecule. In each case, these interactions link the molecules into one-dimensional molecular chains. In (I) and (II), these chains pack so that the pendant alkyl groups are interleaved parallel to one another, maximizing nonbonded C-H contacts. In (III), the alkyl groups are more isolated within the molecular chains and the primary nonbonded contacts between the chains appear to involve the nitro groups not involved in the hydrogen bonding.

1,3-Bis(ethylamino)-2-nitrobenzene, 1,3-bis(n-octylamino)-2-nitrobenzene and 4-ethylamino-2-methyl-1H-benzimidazole.

1,3-Bis(ethylamino)-2-nitrobenzene, C(10)H(15)N(3)O(2), (I), and 1,3-bis(n-octylamino)-2-nitrobenzene, C(22)H(39)N(3)O(2), (II), are the first structurally characterized 1,3-bis(n-alkylamino)-2-nitrobenzenes. Both molecules are bisected though the nitro N atom and the 2-C and 5-C atoms of the ring by twofold rotation axes. Both display intramolecular N-H...O hydrogen bonds between the amine and nitro groups, but no intermolecular hydrogen bonding. The nearly planar molecules pack into flat layers ca 3.4 A apart that interact by hydrophobic interactions involving the n-alkyl groups rather than by pi-pi interactions between the rings. The intra- and intermolecular interactions in these molecules are of interest in understanding the physical properties of polymers made from them. Upon heating in the presence of anhydrous potassium carbonate in dimethylacetamide, (I) and (II) cyclize with formal loss of hydrogen peroxide to form substituted benzimidazoles. Thus, 4-ethylamino-2-methyl-1H-benzimidazole, C(10)H(13)N(3), (III), was obtained from (I) under these reaction conditions. Compound (III) contains two independent molecules with no imposed internal symmetry. The molecules are linked into chains via N-H...N hydrogen bonds involving the imidazole rings, while the ethylamino groups do not participate in any hydrogen bonding. This is the first reported structure of a benzimidazole derivative with 4-amino and 2-alkyl substituents.

N-(n-Dec-yl)-4-nitro-aniline.

N-(n-Dec-yl)-4-nitro-aniline, C(16)H(26)N(2)O(2), crystallizes with two essentially planar mol-ecules in the asymmetric unit. The decyl chains are fully extended in an anti conformation. The mol-ecules pack in planar layers, within which mol-ecules are linked into chains by two approximately linear N-H⋯O hydrogen bonds between the amine N atom and one O atom of the nitro group of an adjacent mol-ecule. These mol-ecular chains propagate via inter-leaving of the decyl chains to form the two dimensional sheets. The sheets are associated exclusively via non-bonded contacts. The structure has features in common with those of other N-alkyl-4-nitro-anilines, but also subtle differences in packing.

5-Aminonaphthalene-1-sulfonic acid and its manganese, nickel and cobalt salts.

5-Ammonionaphthalene-1-sulfonate monohydrate, C10H9NO3S x H2O, contains layers of zwitterionic molecules with the acidic sulfonic acid H atom transferred to the amine N atom. Within each layer, the charged groups (NH3(+) and SO3(-)) are directed to the surface of the layer and are inverted on adjacent molecules. The naphthalene rings in a given layer are all parallel. The layers are held together by N-H...O and O-H...O hydrogen bonds involving the ammonium, sulfonate and water atoms. The Mn and Ni salts crystallize as fully aquated trihydrates, namely hexaaquamanagnese(II) bis(5-aminonaphthalene-1-sulfonate) trihydrate, [Mn(H2O)6](C10H8NO3S)2 x 3 H2O, (II), and hexaaquanickel(II) bis(5-aminonaphthalene-1-sulfonate) trihydrate, [Ni(H2O)6](C10H8NO3S)2 x 3 H2O, (III), in which layers of hexaaquametal(II) complexes alternate with layers of 5-aminonaphthalene-1-sulfonate anions. The cations reside on twofold rotation axes and display regular octahedral coordination. The additional water molecules are found in the inorganic layer between the complex cations, one on a twofold axis and one in a general position. The anions are packed in a herring-bone arrangement with the rings of neighboring rows of anions approximately 43 degrees out of parallel. The NH2 and SO3(-) groups line the surface of the layer, where they participate in numerous hydrogen bonds with the water molecules. Whereas the Mn and Ni salts are orthorhombic, the Co salt, hexaaquacobalt(II) bis(5-aminonaphthalene-1-sulfonate) dihydrate, [Co(H2O)6](C10H8NO3S)2 x 2 H2O, (IV), crystallizes in a triclinic cell of similar dimensions, with the cations situated on centers of inversion. The overall packing is very similar to that of the Mn and Ni salts, with the main differences being the absence of the solvent water molecule on the special position and subtle modifications in the positioning of the anions within their layers. This series of salts is compared with those of the same metals with the 5-aminonaphthalene-2-sulfonate and 4-aminonaphthalene-1-sulfonate isomers, allowing for similarities and differences in packing to be discussed on the basis of the differing substitution of the naphthalene ring and, in some cases, differing degrees of hydration.