New type of single chain magnet: pseudo-one-dimensional chain of high-spin Co(II) exhibiting ferromagnetic intrachain interactions.

Two new six-coordinated high-spin Co(II) complexes have been synthesized through the reactions of Co(II) salts with dipyridylamine (dpamH) and 5-nitro-salicylaldehyde (5-NO2-saloH) or 3-methoxy-salicylaldehyde (3-OCH3-saloH) under argon atmosphere: [Co(dpamH)2(5-NO2-salo)]NO3 (1) and [Co(dpamH)2(3-OCH3-salo)]NO3·1.3 EtOH·0.4H2O (2). According to the crystal packing of compound 1, two coordination cations are linked with two nitrate anions into a cyclic dimeric arrangement via N-H···O and C-H···O hydrogen bonds. In turn, these dimers are assembled into (100) layers through π-π stacking interactions between inversion-center related pyridine rings of the dpamH ligands. The crystal packing of compound 2 reveals a 1D assembly consisting solely from the coordination cations, which is formed by π-π stacking interactions between pyridine rings of one of the dpamH along the [010] and another 1D assembly of the coordination cations and nitrate anions through the N-H···O hydrogen-bonding interactions along the [001] direction. All complexes were magnetically characterized, and a new approximation method was used to fit the magnetic susceptibility data in the whole temperature range 2-300 K on the basis of an empirical expression which allows the treatment of each cobalt(II) ion in axial symmetry as an effective spin S(eff) = 1/2. In zero-field, dynamic magnetic susceptibility measurements show slow magnetic relaxation below 5.5 K for compound 2. The slow dynamics may originate from the motion of broad domain walls and is characterized by an Arrhenius law with a single energy barrier Δr/k(B) = 55(1) K for the [10-1488 Hz] frequency range. In order to reveal the importance of the crystal packing in the SCM behavior, a gentle heating process to 180 °C was carried out to remove the solvent molecules. The system, after heating, undergoes a major but not complete collapse of the network retaining to a small percentage its SCM character.

Synthesis, molecular structure and anticancer activity of 1-allyl-3-amino-2-(4-chloro-2-mercaptobenzenesulphonyl)guanidine derivatives.

A series of 3-allylamino-6-chloro-7-R-1,1-dioxo-1,4,2-benzodithiazines (2a-e) was obtained by the reaction of 6-chloro-3-methylthio-1,4,2-benzodithiazine-1,1-dioxides (1a-e) with allylamine. Selective hydrazinolysis of the allylaminobenzodithiazines (2a-e) gave the appropriate 1-allyl-3-amino-2-(4-chloro-2-mercaptobenzenesulphonyl)guanidines (3a-e) in good yields. The reaction of 3a with dimethylsulphate under alkaline conditions provided the methylthio derivative 4. The structures of these compounds were confirmed on the basis of elemental analysis, spectral data (IR, 1H- and 13C-NMR) and X-ray analysis. Screening data indicated that the compounds 3a and 3d exhibited significant in vitro activities against numerous human tumour cell lines, whereas compounds 3b and 3c showed a moderate activity.

Circular dichroism spectra of the achiral guest N-aryl-N-nitrosamines included in the crystal host matrices of cholic acid.

The crystalline inclusion complexes of cholic acid with three symmetric N-aryl-N-nitrosamines were prepared, and their X-ray structures were solved. As a result of chiral conformations adopted by the enclathrated guest nitrosamines, the solid-state CD spectra were measured in KBr disks. The observed Cotton effect sign, corresponding to the n-pi* transition, was correlated with the helicity of the twisted nitrosamine chromophore conjugated with the N-aryl substituent. In addition, the absolute configuration of the enantiomorphous crystals of N-benzyl-N-nitroso-4-chloroaniline was established on the basis of the solid-state CD and X-ray crystallographic results.

Carbon disulfide promoted reactions of 2-chloro-4,5-dihydro-imidazole with some N-nucleophiles.

The reactions of 2-chloro-4,5-dihydroimidazole 1 with o-substituted anilines and azoles promoted by carbon disulfide have been carried out. Ab initio MO calculations were used to elucidate the mechanism of the reaction of 1 with N-nucleophilic reagents. A facile synthesis of 2-(4,5-dihydroimidazol-2-yl)-1H-indazole 3e bearing structural resemblances to 2-BFI, a potent and selective agonist of imidazoline I2 receptors, is also described. Structure of 3e was confirmed by NMR spectroscopy and X-ray analysis.

Pseudopolymorphism in tetradeca-2,6-O-methyl-beta-cyclodextrin: the crystal structures for two new hydrates-conformational variability in the alkylated beta-cyclodextrin molecule.

Tetradeca-2,6-O-methyl-beta-cyclodextrin, per-2,6-OMe-beta-CD, is an unusual beta-cyclodextrin, beta-CD, derivative because it has a negative thermal solubility coefficient in aqueous solution. This report describes two new crystal structures for hydrates of per-2,6-OMe-beta-CD crystallized at different temperatures: per-2,6-OMe-beta-CD.1.08H(2)O crystallized at 50 degrees C and per-2,6-OMe-beta-CD.14.7H(2)O crystallized at 4 degrees C. The crystal structure for per-2,6-OMe-beta-CD.1.08H(2)O reveals conformational flexibility in the methylated beta-CD molecule; two adjacent glucose residues are disordered as a result of their adopting different tilts with respect to the O(4) plane characterizing the molecule. When one conformation is present there is a water molecule in the lattice (0.5 population parameter); said water is displaced by the methyl of a methoxy substituent when the other conformer is present.

Asymmetric transformation of N-nitrosamines by inclusion crystallization with optically active hosts.

Several N-nitrosopiperidines with chirality solely due to a hindered rotation about the N-N bond were resolved to enantiomers by inclusion crystallization with optically active diols (TADDOLs). The absolute configuration of the guest nitrosamines was deduced from the X-ray crystal structures of the inclusion complexes. The enclathrated nitrosamines were liberated by a competitive complexation of the host diols with piperazine. The optical activity of the resolved nitrosamines is manifested by their CD spectra. A simple chirality rule was proposed for a rationalization of the observed Cotton effect sign corresponding to the n-pi* electronic transition. The optically active nitrosamines are configurationally labile compounds and gradually racemize in solution but they are indefinitely stable in the solid state. The first-order kinetics of the racemization in solution allowed us to assign the N-N rotation barriers by simple polarimetric measurements.

Synthesis, structure and antiaggregatory effects of some N-(4,5-dihydro-1H-imidazol-2-yl)indoles.

A series of 1-(4,5-dihydro-1H-imidazol-2-yl)indole derivatives was prepared in order to evaluate their antiaggregatory activity in human platelets. The compounds 4a-m were prepared by reacting N-aryl-N-(4,5-dihydro-1H-imidazol-2-yl)hydroxylamines (2a-d) with monosubstituted acetylene derivatives 3a-b. Imidazoline derivatives 4 were further acetylated or sulfonylated to give amides 5a-c and sulfonamides 6a-c and 7a-c, respectively. Eight compounds were taken as representative aryliminoimidazoline analogs. Among them only one, 4m, showed a good concentration-dependent action against the primary or alpha 2-adrenoreceptor mediated phase of noradrenaline-induced aggregation in platelets.

Synthesis, structure, and binding of some 2-imidazolines to rat brain alfa-1 and alfa-2-adrenergic receptors.

A series of novel 2-[(2-aminophenyl)imino]imidazolinium salts 3a-d and N-benzyl-N-(4,5-dihydro-imidazol-2-yl)-O-methylhydroxylamine hydrochloride 7a-c were prepared and their structure was determined by IR and NMR spectroscopic data as well as X-ray analysis of the imidazolinium azide salt 3e. Binding evaluation for both alpha 1- and alpha 2-adrenergic receptors in rat brain preparations of these compounds and the previously described alpha-hydroxy-2-aryliminoimidazolines 11a-d, N-(4,5-dihydroimidazol-2-yl)-1,3-2-oxodihydrobenzimidazoles 12a-b, 2-amino-N-(4,5-dihydroimidazol-2-yl)-benzimidazoles 13a-b, and N-(4,5-dihydroimidazol-2-yl)-indoles 14a-b was performed. Among the compounds tested, 2-[(2-amino-4,5-dichlorophenyl)imino]imidazolinium chloride 3c showed highest binding affinity to alpha 2-adrenoreceptors (Ki = 30 nM).

Synthesis, structural characterization and antitumor activity of novel 2,4-diamino-1,3,5-triazine derivatives.

The syntheses, structural elucidation based on NMR spectroscopy and X-ray analysis of 8 as well as antitumor activities of novel 2,4-diamino-1,3,5-triazine derivatives 5 and 7-22 are described. Screenings performed at NCI showed that most derivatives possessed a moderate to strong growth inhibition activity on various tumor panel cell lines between 0.148 and 56.2 microM concentrations. 2-Amino-6-bromomethyl-4-(3,5,5-trimethyl-2-pyrazoline)-1,3,5-triazine 11 showed the most potent antitumor activity with the mean midpoint values of log(10) GI50, log(10) TGI50 and log(10) LC50 of all tests equal to -5.26, -4.81 and -4.37, respectively and therefore, it can be considered as a lead structure for further development of anticancer agents.

Synthesis, structure, and biological activities of some N-(4,5-dihydro-1H-imidazol-2-yl)-1,3-dihydrobenzimidazole derivatives.

A series of novel N-(4,5-dihydroimidazol-2-yl)-1,3-dihydrobenzimidazole derivatives 2a-d, 3a-d and 4a-p were prepared and their structure was determined by IR and NMR spectroscopic data as well as X-ray analysis of carbonitrile 2a. The compounds were studied as potential inhibitors of the human blood platelet aggregation induced by adrenaline or ADP. Compounds of type 3 proved efficacious for the reduction of arterial blood pressure upon intravenous administration to normotensive rats.

Conformational flexibility of serotonin1A receptor ligands from crystallographic data. Updated model of the receptor pharmacophore.

Preparation and affinity to 5-HT1A and 5-HT2A receptors of new buspirone analogues 7-17 are reported. The compounds possess high to low affinity to 5-HT1A and moderate to low to 5-HT2A receptors. The crystal structures have been determined for compounds 11, 12, 13, and 14. For low affinity ligand (15) of 5-HT1A receptor conformational analysis was performed and compared with similar analyses performed for know high (buspirone 1) and very high (WY-48,723 2) affinity ligands of the receptor. Structure-activity relationship is discussed for the affinity to 5-HT1A receptor. A three-point pharmacophore explaining interactions of buspirone-like molecules with the receptor binding site is proposed.

Buspirone analogues as ligands of the 5-HT1A receptor. 1. The molecular structure of buspirone and its two analogues.

An interdisciplinary (X-ray, 1H and 13C NMR, IR, and theoretical quantum mechanical) study on the potent 5-HT1A receptor ligand buspirone (1) and its two structural analogues, mesmar (4,4-dimethyl-1-[4-[4-(2-quinolinyl)-1-piperazinyl]butyl]-2,6- piperidinedione) (2) and kaspar (8-[4-[4-(2-quinolinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane - 7,9-dione) (3), has been reported. The results have shown that buspirone-like molecules should appear in an extended rod-shape form, possessing several potential interaction sites with the receptor.

Crystal structure of 2'-deoxycytidine hemidihydrogenphosphate reveals C+.C base pairs and tight, hydrogen-bonded (H2PO4-)infinity columns (1).

2'-Deoxycytidine hemidihydrogenphosphate has been crystallized in the hexagonal space group P6(2) with a = 25.839(3), c = 12.529(1) A. The structure has been solved using the Patterson search method. The asymmetric unit contains two protonated, base-paired 2'-deoxycytidine dimers and two H2PO4- anions. The C+.C base pairs are composed of a protonated and a neutral species each and are triple H-bonded, the central N(3) ... N(3) bonds being 2.850(7) and 2.884(5) A. The conformations of the four nucleosides fall in the same category (sugar puckers 2'-endo, glycosidic links anti) but in one of them the glycosidic torsion angle is quite low with consequences in other geometrical parameters. The H2PO4- anions are located on twofold axes and form two types of tight columns with P ... P separations about 4.18 A. The neighboring units along a column are linked via two very short O ... H ... O hydrogen bonds (O ... O about 2.49 A) leading to effective equalization of the P-O bonds. The base pairs of the two dC+.dC cations are coplanar and form layers perpendicular to the phosphate columns repeating every c/3. Within the layers, the dimers form a network through O(5') ... O(2) hydrogen bonds but their primary intermolecular interactions have the form of H-bond anchors [N(4)-H ... O-P and O(3')-H ... O-P] to the phosphate groups.

Conformation of cyclo-(D-phenylalanyl-trans-4-fluoro-D-prolyl).

cyclo(D-Phenylalanyl-trans-4-fluoro-D-prolyl), c(D-Phe-D-FPro), was synthesized and its conformation determined both in solution and in the solid state by 1H NMR and X-ray analysis, respectively. In the crystals the 2.5-diketopiperazine (DKP) ring assumes the uncommon conformation, for cyclodipeptides containing Pro residue, of a flattened chair, which seemingly results from a compromise between, on the one hand, the DKP-aromatic intramolecular ring-ring attraction (folding), requiring the C alpha--C beta bond of the Phe to be axial, and, on the other hand, the intrinsic tendency of the Pro residue to have its C alpha--C beta bond equatorial. Unlike the solid state, the 1H NMR data in CDCl3 and C6D6 demonstrate that in both solutions the DKP ring assumes a boat-like shape, typical for the Pro-containing cyclodipeptides, with the equatorial C alpha--C beta bonds in both amino acid residues, which preclude ring-ring folding. A similar conformation was encountered in the closest analog of c(D-Phe-D-FPro), viz, in c(Phe-Pro), both in solution (21, 22, 26) and in the solid state (12). A subtle interplay of intramolecular interactions introduced into a cyclodipeptide by a Pro-type and a Phe-type residue is emphasized.

The X-ray structure and absolute configuration of the anticancer drug (+)-4-ketocyclophosphamide.

4-Ketocyclophosphamide (4-keto CP), C7H12Cl2N2O3P, monoclinic, P2(1), a = 11.909 (2), b = 10.254 (1), c = 9.873 (1) A, beta = 91.08 (1) degrees, V = 1205.45 (3) A3 Z = 4, Dc = 1.51 Mg-m-3, Cu K alpha, lambda = 1.54178 A, alpha 25 = +53.8 degrees (c = 3.0, MeOH), m.p. 107 degrees C, mu = 61.8 cm-1, F (000) = 564, R = 0.064 for 2961 observed reflexions with I greater than 1.96 sigma(I). Dextrarotatory enantiomer of 4-keto CP has S configuration at the stereogenic center. One of the two crystallographically independent molecules is disordered both in a six-membered ring and in --N(CH2CH2Cl)2 moiety. With the exception of a less populated conformer of a disordered molecule, 4-keto CP molecules adopt a conformation in which 1,3,2-oxazophosphorinane ring is in the sofa form with C(6) deviating from the plane through the remaining five ring atoms while an exocyclic N atom with its three substituents is nearly coplanar with the phosphoryl oxygen atom O(8). In a less populated conformer, the six membered ring takes the form of sofa with C(5) as a flap while an exocyclic N atom and its substituents are oriented toward the P--N(3) bond.