Phenyl-ring disorder in the two-dimensional hydrogen-bonded structure of the 1:1 proton-transfer salt of the diazo-dye precursor 4-(phenyldiazenyl)aniline (aniline yellow) with L-tartaric acid

The structure of the 1:1 proton-transfer compound from the reaction of L-tartaric acid with the azo-dye precursor aniline yellow [4-(phenylazo)aniline], 4-(phenyldiazenyl)anilinium hydrogen 2R,3R-tartrate C12H12N3+ . C4H6O6- has been determined at 200 K. The asymmetric unit of the compound contains two independent phenylazoanilinium cations and two hydrogen L-tartrate anions. The structure is unusual in that all four phenyl rings of both cations have identical 50% rotational disorder. The two hydrogen L-tartrate anions form independent but similar chains through head-to-tail carboxylic O--H...O~carboxyl~ hydrogen bonds [graph set C7] which are then extended into a two-dimensional hydrogen-bonded sheet structure through hydroxyl O--H...O hydrogen-bonding links. The anilinium groups of the phenyldiazenyl cations are incorporated into the sheets and also provide internal hydrogen-bonding extensions while their aromatic tails layer in the structure without significant interaction except for weak \p--\p interactions [minimum ring centroid separation, 3.844(3) \%A]. The hydrogen L-tartrate residues of both anions have the common short intramolecular hydroxyl O--H...O~carboxyl~ hydogen bonds. This work has provided a solution to the unusual disorder problem inherent in the structure of this salt as well as giving another example of the utility of the hydrogen tartrate in the generation of sheet substructures in molecular assembly processes.

Low-dimensional hydrogen-bonded structures in the 1:1 and 1:2 proton-transfer compounds of 4,5-dichlorophthalic acid with the aliphatic Lewis bases triethylamine, diethylamine, n-butylamine and piperidine

The structures of proton-transfer compounds of 4,5-dichlorophthalic acid (DCPA) with the aliphatic Lewis bases triethylamine, diethylamine, n-butylamine and piperidine, namely triethylaminium 2-carboxy-4,5-dichlorobenzoate C~6~H~16~N^+^ C~8~H~3~Cl~2~O~4~^-^ (I), diethylaminium 2-carboxy-4,5-dichlorobenzoate C~4~H~12~N^+^ C~8~H~3~Cl~2~O~4~^-^ (II), bis(n-butylaminium) 4,5-dichlorophthalate monohydrate 2(C~4~H~12~N^+^) C~8~H~2~Cl~2~O~4~^2-^ . H~2~O (III) and bis(piperidinium) 4,5-dichlorophthalate monohydrate 2(C~5~H~12~N^+^) C~8~H~2~Cl~2~O~4~^2-^ . H~2~O (IV)have been determined at 200 K. All compounds have hydrogen-bonding associations giving in (I) discrete cation-anion units, linear chains in (II) while (III) and (IV) both have two-dimensional structures. In (I) a discrete cation-anion unit is formed through an asymmetric R2/1(4) N+-H...O,O' hydrogen-bonding association whereas in (II), one-dimensional chains are formed through linear N-H...O associations by both aminium H donors. In compounds (III) and (IV) the primary N-H...O linked cation-anion units are extended into a two-dimensional sheet structure via amide N-H...O(carboxyl) and ...O(carbonyl) interactions. In the 1:1 salts [(I) and (II)], the hydrogen 4,5-dichlorophthalate anions are essentially planar with short intramolecular carboxylic acid O-H...O(carboxyl) hydrogen bonds [O...O, 2.4223(14) and 2.388(2)A respectively]. This work provides a further example of the uncommon zero-dimensional hydrogen-bonded DCPA-Lewis base salt and the one-dimensional chain structure type, while even with the hydrate structures of the 1:2 salts with the primary and secondary amines, the low dimensionality generally associated with 1:1 DCPA salts is also found.

Anhydrous 1:1 proton-transfer compounds of isonipecotamide with picric acid and 3,5-dinitrosalicylic acid: 4-carbamoylpiperidinium 2,4,6-trinitrophenolate and two polymorphs of 4-carbamoylpiperidinium 2-carboxy-4,6-dinitrophenolate

The structures of the anhydrous 1:1 proton-transfer compounds of isonipecotamide (4-carbamoylpiperidine) with picric acid and 3,5-dinitrosalicylic acid, namely 4-carbamoylpiperidinium 2,4,6-trinitrophenolate, C6H13N2O8+ C6H2N3O7- (I) and 4-carbamoylpiperidinium 2-carboxy-4,6-dinitrophenolate, C6H13N2O8+ C7H3N2O7-: two forms, the monoclinic alpha-polymorph (II) and the triclinic beta-polymorph (III) have been determined at 200 K. All compounds form hydrogen-bonded structures, one-dimensional in (II), two-dimensional in (I) and three-dimensional in (III). In (I), the cations form centrosymmetric cyclic head-to-tail hydrogen-bonded homodimers [graph set R2/2(14)] through lateral duplex piperidinium N---H...O(amide) interactions. These dimers are extended into a two-dimensional network structure through further interactions with anion phenolate-O and nitro-O acceptors, including a direct symmetric piperidinium N-H...O(phenol),O(nitro) cation--anion association [graph set R2/1(6)]. The monoclinic polymorph (II) has a similar R2/1(6) cation-anion hydrogen-bonding interaction to (I) but with an additional conjoint symmetrical R1/2(4) interaction as well as head-to-tail piperidinium N-H...O(amide) O hydrogen bonds and amide N-H...O(carboxyl) hydrogen bonds, give a network structure which include large R3/4(20) rings. The hydrogen bonding in the triclinic polymorph (III) is markedly different from that of monoclinic (II). The asymmetric unit contains two independent cation-anion pairs which associate through cyclic piperidinium N-H...O,O'(carboxyl) interactions [graph set R2/1(4)]. The cations also show the zig-zag head-to-tail piperidinium N-H...O(amide) hydrogen-bonded chain substructures found in (II) but in addition feature amide N-H...O(nitro) and O(phenolate) and amide N-H...O(nitro) associations. As well there is a centrosymmetric double-amide N-H...O(carboxyl) bridged bis(cation-anion) ring system [graph set R2/4(8)] in the three-dimensional framework. The structures reported here demonstrate the utility of the isonipecotamide cation as a synthon with previously unrecognized potential for structure assembly applications. Furthermore, the structures of the two polymorphic 3,5-dinitrosalicylic acid salts show an unusual dissimilarity in hydrogen-bonding characteristics, considering that both were obtained from identical solvent systems.

Hydrogen bonding in the anhydrous 1:1 proton-transfer compounds of isonipecotamide with nitro-substituted benzoic acids: the salts of the three isomeric mononitrobenzoic acids and of 3,5-dinitrobenzoic acid

The structures of the anhydrous 1:1 proton-transfer compounds of isonipecotamide (piperidine-4-carboxamide) with the three isomeric mononitro-substituted benzoic acids and 3,5-dinitrobenzoic acid, namely 4-carbamoylpiperidinium 2-nitrobenzoate (I), 4-carbamoylpiperidinium 3-nitrobenzoate (II), 4-carbamoylpiperidinium 4-nitrobenzoate (III), (C6H13N2O+ C7H4NO4-) and 4-carbamoylpiperidinium 3,5-dinitrobenzoate (IV) (C6H13N2O+ C7H5N2O6-)respectively, have been determined at 200 K. All salts form hydrogen-bonded structures: three-dimensional in (I), two-dimensional in (II) and (III) and one-dimensional in (IV). Featured in the hydrogen bonding of three of these [(I), (II) and (IV)] is the cyclic head-to-head amide--amide homodimer motif [graph set R2/2~(8)] through a duplex N---H...O association, the dimer then giving structure extension via either piperidinium or amide H-donors and carboxylate-O and in some examples [(II) and (IV)], nitro-O atom acceptors. In (I), the centrosymmetric amide-amide homodimers are expanded laterally through N-H...O hydrogen bonds via cyclic R2/4(8) interactions forming ribbons which extend along the c cell direction. These ribbons incorporate the 2-nitrobenzoate cations through centrosymmetric cyclic piperidine N-H...O(carboxyl) associations [graph set R4/4(12)], giving inter-connected sheets in the three-dimensional structure. In (II) in which no amide-amide homodimer is present, duplex piperidinium N-H...O(amide) hydrogen-bonding homomolecular associations [graph set R2/2(14)] give centrosymmetric head-to-tail dimers. Structure extension occurs through hydrogen-bonding associations between both the amide H-donors and carboxyl and nitro O-acceptors as well as a three-centre piperidinium N-H...O,O'(carboxyl) cyclic R2/1(4) association giving the two-dimensional network structure. In (III), the centrosymmetric amide-amide dimers are linked through the two carboxyl O-atom acceptors of the anions via bridging piperidinium and amide N-H...O,O'...H-N(amide) hydrogen bonds giving the two-dimensional sheet structure which features centrosymmetric cyclic R4/4(12) associations. In (IV), the amide-amide dimer is also centrosymmetric with the dimers linked to the anions through amide N-H...O(nitro) interactions. The piperidinium groups extend the structure into one-dimensional ribbons via N-H...O(carboxyl) hydrogen bonds. The structures reported here further demonstrate the utility of the isonipecotamide cation in molecular assembly and highlight the efficacy of the cyclic R2/2(8) amide-amide hydrogen-bonding homodimer motif in this process and provide an additional homodimer motif type in the head-to-tail R2/2(14) association.

Hydrogen bonding in proton-transfer compounds of 5-sulfosalicylic acid with a series of aliphatic nitrogen Lewis bases

The crystal structures of the proton-transfer compounds of 5-sulfosalicylic acid (3-carboxy-4-hydroxybenzenesulfonic acid) with the aliphatic nitrogen Lewis bases, hydroxylamine, triethylamine, pyrrolidine, morpholine, N-methylmorpholine and piperazine, viz. hydroxyammonium 3-carboxy-4-hydroxybenzenesulfonate (1), triethylaminium 3-carboxy-4-hydroxybenzenesulfonate (2), pyrrolidinium 3-carboxy-4-hydroxybenzenesulfonate monohydrate (3), morpholinium 3-carboxy-4-hydroxybenzenesulfonate monohydrate (4), N-methylmorpholinium 3-carboxy-4-hydroxybenzenesulfonate monohydrate (5) and piperazine-1,4-diium bis(3-carboxy-4-hydroxybenzenesulfonate) hexahydrate (6) have been determined and their comparative structural features and hydrogen-bonding patterns described. Crystals of 4 are triclinic, space group P-1 while the remainder are monoclinic with space group either P21/c (1 - 3) or P21/n (5, 6). Unit cell dimensions and contents are: for 1, a = 5.0156(3), b = 10.5738(6), c = 18.4785(9) Å, β = 96.412(5)o, Z = 4; for 2, a = 8.4998(4), b = 12.3832(6), c = 15.4875(9) Å, β = 102.411(5)o, Z = 4; for 3, a = 6.8755(2), b = 15.5217(4), c = 12.8335(3) Å, β = 92.074(2)o, Z = 4; for 4, a = 6.8397(2), b = 12.9756(5), c = 15.8216(6) Å, α = 90.833(3), β = 95.949(3), γ = 92.505(3)o, Z = 4; for 5, a = 7.0529(3), b = 13.8487(7), c = 15.6448(6) Å, β = 90.190(6)o, Z = 4; for 6, a = 7.0561(2), b = 15.9311(4), c = 12.2102(3) Å, β = 100.858(3)o, Z = 2. The hydrogen bonding generates structures which are either two-dimensional (2 and 5) or three-dimensional (1, 3, 4 and 6). Compound 6 represents the third reported structure of a salt of 5-sulfosalicylic acid having a dicationic piperazine species.

Pseudo-merohedral twinning in the structure of the hydrated 1:1 proton-transfer compound of 5-sulfosalicylic acid with 4-aminopyridine

The structure of the pseudo-merohedrally twinned crystal of the 1:1 proton-transfer compound of 5-sulfosalicylic acid (3-carboxy-4-hydroxybenzenesulfonic acid) with 4-aminopyridine: 4-aminopyridinium 3-carboxy-4-hydroxybenzenesulfonate sesquihydrate has been determined at 180 K and the hydrogen-bonding pattern is described. Crystals of the compound are monoclinic with space group P21/c, with unit cell dimensions a = 35.2589(8), b = 7.1948(1), c = 24.5851(5) Å, β = 110.373(2)o, and Z = 16. The monoclinic asymmetric unit comprises four cation-anion pairs and six water molecules of solvation with only the pyridinium cations having pseudo-symmetry as a result of inter-cation aromatic ring π-π stacking effects. Extensive hydrogen bonding gives a three-dimensional framework structure.

Proton-transfer compounds of isnipecotamide with the aromatic dicarboxylic acids 4-nitrophthalic, 4,5-dichlorophthalic, 5-nitroisophthalic and terephthalic acid

The structures of the 1:1 proton-transfer compounds of isonipecotamide (4-piperidinecarboxamide) with 4-nitrophthalic acid, 4-carbamoylpiperidinium 2-carboxy-4-nitrobenzoate, C6H13N2O8+ C8H4O6- (I), 4,5-dichlorophthalic acid, 4-carbamoylpiperidinium 2-carboxy-4,5-dichlorobenzoate, C6H13N2O8+ C8H3Cl2O4- (II) and 5-nitroisophthalic acid, 4-carbamoylpiperidinium 3-carboxy-5-nitrobenzoate, C6H13N2O8+ C8H4O6- (III) as well as the 2:1 compound with terephthalic acid, bis(4-carbamoylpiperidinium)benzene-1,2-dicarboxylate dihydrate, 2(C6H13N2O8+) C8H4O42- . 2H2O (IV)have been determined at 200 K. All salts form hydrogen-bonded structures, one-dimensional in (II) and three-dimensional in (I), (III) and (IV). In (I) and (III) the centrosymmetric R2/2(8) cyclic amide-amide association is found while in (IV) several different types of water-bridged cyclic associations are present [graph sets R2/4(8), R3/4(10), R4/4(12), R3/3(18) and R4/6(22)]. The one-dimensional structure of (I), features the common 'planar' hydrogen 4,5-dichlorophthalate anion together with enlarged cyclic R3/3(13) and R3/4(17) associations. With the structures of (I) and (III) the presence of head-to-tail hydrogen phthalate chain substructures is found. In (IV) head-to-tail primary cation-anion associations are extended longitudinally into chains through the water-bridged cation associations and laterally by piperidinium N-H...O(carboxyl) and water O-H...O(carboxyl) hydrogen bonds. The structures reported here further demonstrate the utility of the isonipecotamide cation as a synthon for the generation of stable hydrogen-bonded structures. An additional example of cation--anion association with this cation is also shown in the asymmetric three-centre piperidinium N-H...O,O'(carboxyl) interaction in the first-reported structure of a 2:1 isonipecotamide-carboxylate salt.

2,3-Dimethoxy-10-oxostrychnidinium 2-(2,4,6-trinitroanilino)benzoate monohydrate : a 1:1 proton-transfer salt of brucine with o-picraminobenzoic acid

In the structure of the 1:1 proton-transfer compound of brucine with 2-(2,4,6-trinitroanilino)benzoic acid C23H27N2O4+ . C13H7N4O8- . H~2~O, the brucinium cations form the classic undulating ribbon substructures through overlapping head-to-tail interactions while the anions and the three related partial water molecules of solvation (having occupancies of 0.73, 0.17 and 0.10) occupy the interstitial regions of the structure. The cations are linked to the anions directly through N-H...O(carboxyl) hydrogen bonds and indirectly by the three water molecules which form similar conjoint cyclic bridging units [graph set R2/4(8)] through O-H...O(carbonyl) and O(carboxyl) hydrogen bonds, giving a two-dimensional layered structure. Within the anion, intramolecular N-H...O(carboxyl) and N H...O(nitro) hydrogen bonds result in the benzoate and picrate rings being rotated slightly out of coplanarity inter-ring dihedral angle 32.50(14)\%]. This work provides another example of the molecular selectivity of brucine in forming stable crystal structures and also represents the first reported structure of any form of the guest compound 2-(2,4,6-trinitroanilino)benzoic acid.

Structural Systematics of the Anhydrous 1:1 Proton-Transfer Compounds of 3,5-Dinitrosalicylic Acid with Aniline and Monosubstituted Anilines

The crystal structures of the proton-transfer compounds of 3,5-dinitrosalicylic acid (DNSA) with a series of aniline-type Lewis bases [aniline, 2-hydroxyaniline, 2-methoxyaniline, 3-methoxyaniline, 4-fluoroaniline, 4-chloroaniline and 2-aminoaniline] have been determined and their hydrogen-bonding systems analysed. All are anhydrous 1:1 salts: [(C6H8N)+(C7H3N2O7)-], (1), [(C6H8NO)+(C7H3N2O7)-], (2), [(C7H10NO)+(C7H3N2O7)-], (3), [(C7H10NO)+(C7H3N2O7)-], (4), [(C6H7FN)+(C7H3N2O7)-], (5), [(C6H7ClN)+(C7H3N2O7)-], (6), and [(C6H9N2)+(C7H3N2O7)-], (7) respectively. Crystals of 1 and 6 are triclinic, space group P-1 while the remainder are monoclinic with space group either P21/n (2, 4, 5 and 7) or P21 (3). Unit cell dimensions and contents are: for 1, a = 7.2027(17), b = 7.5699(17), c = 12.9615(16) Å, α = 84.464(14), β = 86.387(15), γ = 75.580(14)o, Z = 2; for 2, a = 7.407(3), b = 6.987(3), c = 27.653(11) Å, β = 94.906(7)o, Z = 4; for 3, a = 8.2816(18), b = 23.151(6), c = 3.9338(10), β = 95.255(19)o, Z = 2; for 4, a = 11.209(2), b = 8.7858(19), c = 15.171(3) Å, β = 93.717(4)o, Z = 4; for 5, a = 26.377(3), b = 10.1602(12), c = 5.1384(10) Å, β = 91.996(13)o, Z = 4; for 6, a = 11.217(3), b = 14.156(5), c = 4.860(3) Å, α = 99.10(4), β = 96.99(4), γ = 76.35(2)o, Z = 2; for 7, a = 12.830(4), b = 8.145(3), c = 14.302(4) Å, β = 102.631(6)o, Z = 4. In all compounds at least one primary linear intermolecular N+-H…O(carboxyl) hydrogen-bonding interaction is present which, together with secondary hydrogen bonding results in the formation of mostly two-dimensional network structures, exceptions being with compounds 4 and 5 (one-dimensional) and compound 6 (three-dimensional). In only two cases [compounds 1 and 4], are weak cation-anion or cation-cation π-π interactions found while weak aromatic C-H…O interactions are insignificant. The study shows that all compounds fit the previously formulated classification scheme for primary and secondary interactive modes for proton-transfer compounds of 3,5-dinitrosalicylic acid but there are some unusual variants.

Hydrogen-bonding in the structures of the hydrated proton-transfer compounds of isonipecotamide with the isomeric indole-2 and indole-3-carboxylic acids

The structures of two hydrated proton-transfer compounds of 4-piperidinecarboxamide (isonipecotamide) with the isomeric heteroaromatic carboxylic acids indole-2-carboxylic acid and indole-3-carboxylic acid, namely 4-carbamoylpiperidinium indole-2-carboxylate dihydrate (1) and 4-carbamoylpiperidinium indole-3-carboxylate hemihydrate (2) have been determined at 200 K. Crystals of both 1 and 2 are monoclinic, space groups P21/c and P2/c respectively with Z = 4 in cells having dimensions a = 10.6811(4), b = 12.2017(4), c = 12.5456(5) Å, β = 96.000(4)o (1) and a = 15.5140(4), b = 10.2908(3), c = 9.7047(3) Å, β = 97.060(3)o (2). Hydrogen-bonding in 1 involves a primary cyclic interaction involving complementary cation amide N-H…O(carboxyl) anion and anion hetero N-H…O(amide) cation hydrogen bonds [graph set R22(9)]. Secondary associations involving also the water molecules of solvation give a two-dimensional network structure which includes weak water O-H…π interactions. In the three-dimensional hydrogen-bonded structure of 2, there are classic centrosymmetric cyclic head-to-head hydrogen-bonded amide-amide interactions [graph set R22(8)] as well as lateral cyclic amide-O linked amide-amide extensions [graph set R24(8)]. The anions and the water molecule, which lies on a twofold rotation axis, are involved in secondary extensions.

Incipient neurovulnerability and neuroprotection in early psychosis : a proton spectroscopy study of the anterior hippocampus at 3Tesla

Programmed cell death (PCD) and progenitor cell generation (of glial and in some brain areas also neuronal fate) in the CNS is an active process throughout life and is generally not associated with gliosis which means that PCD can be pathologically silent. The striking discovery that progenitor cell generation (of glial and in some brain areas neuronal fate) is widespread in the adult CNS (especially the hippocampus) suggest a much more dynamic scenario than previously thought and transcends the dichotomy between neurodevelopmental and neurodegenerative models of schizophrenia and related disorders. We suggest that the regulatory processes that control the regulation of PCD and the generation of progenitor cells may be disturbed in the early phase of psychotic disorders underpinning a disconnectivity syndrom at the onset of clinically overt disorders. An ongoing 1H-MRS study of the anterior hippocampus at 3 Tesla in mostly drug-naive first-episode psychosis patients suggests no change in NAA, but significant increases in myo-inositol and lactate. The data suggests that neuronal integrity in the anterior hippocampus is still intact at the early stage of illness or mainly only functionally impaired. However the increase in lactate and myo-inositol may reflect a potential disturbance of generation and PCD of progenitor cells (of glial and in selected brain areas also neuronal fate) at the onset of psychosis. If true the use of neuroprotective agents such as lithium or eicosapentaenoic acid (which inhibit PCD and support cell generation)in the early phase of psychotic disorders may be a potent treatment avenue to explore.

Antiproton induced DNA damage : proton like in flight, carbon-ion light near rest

Biological validation of new radiotherapy modalities is essential to understand their therapeutic potential. Antiprotons have been proposed for cancer therapy due to enhanced dose deposition provided by antiproton-nucleon annihilation. We assessed cellular DNA damage and relative biological effectiveness (RBE) of a clinically relevant antiproton beam. Despite a modest LET (~19 keV/μm), antiproton spread out Bragg peak (SOBP) irradiation caused significant residual γ-H2AX foci compared to X-ray, proton and antiproton plateau irradiation. RBE of ~1.48 in the SOBP and ~1 in the plateau were measured and used for a qualitative effective dose curve comparison with proton and carbon-ions. Foci in the antiproton SOBP were larger and more structured compared to X-rays, protons and carbon-ions. This is likely due to overlapping particle tracks near the annihilation vertex, creating spatially correlated DNA lesions. No biological effects were observed at 28–42 mm away from the primary beam suggesting minimal risk from long-range secondary particles.