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HIV-1 integrase (IN) has been validated as an attractivetargetfor the treatment of HIV/AIDS. Several studies have confirmed thatthe metal binding function is a crucial feature in many of the reportedIN inhibitors. To provide new insights on the metal chelating mechanismof IN inhibitors, we prepared a series of metal complexes of two ligands(HL1and HL2), designed as representative modelsof the clinically used compounds raltegravir and elvitegravir. Potentiometricmeasurements were conducted for HL2in the presence ofMg(II), Mn(II), Co(II), and Zn(II) in order to delineate a metal speciationmodel. We also determined the X-ray structures of both of the ligandsand of three representative metal complexes. Our results support thehypothesis that several selective strand transfer inhibitors preferentiallychelate one cation in solution and that the metal complexes can interactwith the active site of the enzyme. [ABSTRACT FROM AUTHOR]

A new series of half-sandwich ruthenium(II) complexes containing p-aminobenzoic acids (4-aminobenzoic acid and 4-aminocynnamic acid) and different arene ligands (benzene, p-cymene, and indane) have been synthesized and fully characterized giving particular attention to the analysis of the generated crystalline supramolecular architectures. A careful design of the molecular building blocks allows a perfect match to be reached between hydrogen bond donors and acceptors thus leading to the construction of crystalline wheel-and-axle metal–organic (WAAMO) systems, where the wheels are the half-sandwich units [(arene)RuCl2] and the axles are based on the cyclic dimerization of the COOH functions of the aminobenzoic ligands. The R22(8) cyclic pattern is however conserved only in absence of hydrogen bond donor crystallization solvents, which, when present, tend to insert between the COOH group and a Cl–Ru moiety with formation of hydrates or solvates. Far more robust is the supramolecular synthon based on the coupling involving the Ru–NH2function as donor and the RuCl2group as acceptor, which has been found in five out of seven X-ray structures reported in this work. The porosity of the WAAMOs can be modulated acting on the steric requirements of the arene ligand and on the length of the covalent segment of the central supramolecular axle. [ABSTRACT FROM AUTHOR]

The X-ray structure of the half-sandwich Ru(ii) complex [(p-cymene)Ru(κN-INA)Cl2] (INA = isonicotinic acid) (1α) does not show the expected cyclic dimerization of the carboxylic functions of INA. The good hydrogen bond accepting character of the chloride ligand in fact, leads to the formation of Ru–ClHOOC intermolecular hydrogen bonded chains. Interestingly, 1αquickly converts into the hydrated form [(p-cymene)Ru(κN-INA)Cl2]H2O (1·H2O) once exposed to water vapours through a heterogeneous solid-gas reaction. In the X-ray structure of 1·H2Otwo water molecules bridge two carboxylic functions of two different organometallic entities, giving rise to a R44(12) cyclic dimer. The 1αto 1·H2Otransformation occurs smoothly even when the first is exposed to vapours of absolute ethanol, whose water content is not higher than 0.2%. The thermally induced dehydration of 1·H2Odoes not give 1αback, but rather it leads to a not yet defined transient species (1γ) which finally transforms into a polymorphic form of 1α, whose solid state structure has been solved by X-ray powder diffraction analysis (1β). [ABSTRACT FROM AUTHOR]

New coordination compounds of general formula Zn(ligand)2X2(ligand = 2,6-diphenylphenol 4-pyridyl aldimine; X = Cl, Br, and I) have been synthesised and structurally characterized. They are analogous of palladium wheel-and-axle diols (waads), that have high propensity to include small guest molecules into their lattice, but the tetrahedral coordination of zinc ion bends their molecular axle. Here we demonstrate that the tuning of the molecular shape by axle bending enables to achieve a good self-packing efficiency, with loss of the clathrating properties of the material. In particular, Zn(ligand)2X2waadsself assemble to form a fourfold interpenetrated superdiamondoid network with a close-packed structure. [ABSTRACT FROM AUTHOR]

The syntheses, crystal structures and solid-state inclusion properties of 3- and 2-pyridyl 3,5-diphenyl-4-hydroxy iminophenols are reported. Their solid-state organization is based on supramolecular head-to-tail chains sustained by O−H···N hydrogen bonds. It is shown that the position of the pyridinic nitrogen is crucial to determine the inclusion propensity. Although formation of nonsolvated close packed networks is observed for both compounds, the 2-pyridyl iminophenol derivative is also able to form nanochannels hosting arrays of guest molecules (toluene, acetone, chloroform). Most interestingly the toluene solvate occurs in two concomitant polymorphs, presenting different channel arrangements, whose properties are studied also by means of high-pressure X-ray diffraction. Thermal analyses are used to determine the kinetics of desolvation of all solvates, whose thermal behavior is correlated with their supramolecular structures. [ABSTRACT FROM AUTHOR]

The synthesis and the crystal structures of several 4-pyridyl imino compounds are reported. Their solid-state organization is based on head-to-tail chains sustained by O–HN hydrogen bonds; the supramolecular arrangement is analysed by means of the Hirshfeld surfaces and of the corresponding 2D-fingerprint plots. The co-crystallization between 4-aminobenzyl alcohol and 4-acetylpyridine is analysed, correlating reactivity trends and structural characters. In this context, the single crystal X-ray diffraction analyses of 4-aminobenzyl alcohol and 3,5-diphenyl-4-hydroxyaniline are also reported. [ABSTRACT FROM AUTHOR]

Previously, we synthesized a series of β-diketo acid metal complexes as novel HIV-1 integrase (IN) inhibitors (J. Med. Chem.2006, 46, 4248−4260). Herein, a further extension of this study is reported. First, detailed docking studies were performed in order to investigate the mode of binding in the active site of the free ligands and of their metal complexes. Second, a series of potentiometric measurements were conducted for two diketo acids chosen as model ligands, with Mn2+and Ca2+, in order to outline a speciation model. Third, we designed and synthesized a new set of complexes with different stoichiometries and tested them in an in vitro assay specific for IN. Finally, we obtained the first X-ray structure of a metal complex with HIV-1 IN inhibition activity. Analysis of these results supports the hypothesis that the diketo acids could act as complexes and form complexes with the metal ions on the active site of the enzyme. [ABSTRACT FROM AUTHOR]

New metal–organic wheel and axle diols of general formula [Pd(ligand)2X2] (X = Cl, Br, I) are designed and synthesised, with the aim to study their inclusion properties. In particular, the overall shape of the complexes (bulkiness of the terminal groups, length of the axle) is varied by a judicious choice of the ligands and the effects of these changes on the packing are investigated. By means of the X-ray single crystal structure determination of several mono- and bis-solvate complexes, it was possible to hypothesize the structural rearrangements that go with the release of the guest. [ABSTRACT FROM AUTHOR]

In this work, we report on a non-solvate and on a new solvate forms of rifamycin S, demonstrating that another stable conformation of the active molecule exists and it may be isolated by planning the crystallization conditions. In fact, in these structures rifamycin S has a previously uncharacterised, bent conformation: implications of these findings on the models used to explain rifamycin activity are discussed. Polymorphism has also been reported for the rifamycin-based antibiotic rifaximin, but without single-crystal X-ray diffraction characterization. Here the structure of a tetrahydrate form of rifaximin is discussed; confirming the flexibility of the drug, the two independent molecules in the unit cell are an example of conformational isomorphism. [ABSTRACT FROM AUTHOR]

The crystal organization of Zn(LOH)2X2 (LOH = α-(4-pyridyl)benzhydrol) shows an abrupt change on passing from X = Cl (1) and X = Br (2) to X = I (3). The smaller and more electronegative halides (1, 2) participate in –OH⋯X hydrogen bonds giving an overall arrangement of the structures in bidimensional sheets where the zinc atoms behave as distorted square nodes in the network topology. In 3 the iodine atom switches the basic supramolecular synthon from –OH⋯X to a tetrahedral –(OH)4 nest assembled by –OH⋯OH hydrogen bonds, giving a non-covalent diamondoid network where the metal acts as a spacer. This (OH)4 nest constitutes a relatively robust supramolecular synthon whose tetrahedral topology arises from self recognition between the molecules, without the need of a central templating element. [ABSTRACT FROM AUTHOR]

Trichlorostannyl complexes M(SnCl 3)(Tp)L(PPh 3) ( 1, 2) and M(SnCl 3)(Cp)L(PPh 3) ( 5, 6) [M = Ru, Os; L = P(OMe) 3( a), P(OEt) 3( b), PPh(OEt) 2( c), PPh 3( d)] were prepared by allowing chloro complexes MCl(Tp)L(PPh 3) and MCl(Cp)L(PPh 3) to react with an excess of SnCl 2·2H 2O in ethanol. Treatment of trichlorostannyl complexes 1, 2, 5, and 6with NaBH 4in ethanol yielded tin trihydride derivatives M(SnH 3)(Tp)L(PPh 3) ( 3, 4) and M(SnH 3)(Cp)L(PPh 3) ( 7, 8). Reaction of these complexes with CCl 4gave the trichlorostannyl precursors 1, 2, 5, and 6. Hydridochlorostannyl intermediates Os(SnH 2Cl)(Tp)[P(OMe) 3](PPh 3) ( 9a) and Os(SnHCl 2)(Tp)[P(OMe) 3](PPh 3) ( 10a) were also obtained. Reaction of trihydridostannyl complexes M(SnH 3)(Tp)L(PPh 3) ( 3, 4) with CO 2(1 atm) led to hydridobis(formate) derivatives M[SnH{OC(H)O} 2](Tp)L(PPh 3) ( 11). In contrast, reaction of the related complexes M(SnH 3)(Cp)L(PPh 3) ( 7, 8) with CO 2(1 atm) led to the binuclear OH-bridging bis(formate) derivatives [M[Sn{OC(H)O} 2(μ-OH)](Cp)L(PPh 3)] 2( 12, 13). A reaction path for the formation of 12and 13, involving the mononuclear tin hydride complex M[SnH{OC(H)O} 2](Cp)L(PPh 3), is discussed. The X-ray crystal structure of 12bis reported. Chlorobis(methyl)stannyl Ru(SnClMe 2)(Cp)[P(OEt) 3](PPh 3) ( 15b) and trimethylstannyl complexes M(SnMe 3)(Tp)[P(OMe) 3](PPh 3) ( 14a) and M(SnMe 3)(Cp)[P(OEt) 3](PPh 3) ( 16b, 17b) were prepared by allowing trichlorostannyl compounds 1, 2, 5, and 6to react with MgBrMe in diethyl ether. Trialkynylstannyl derivatives M[Sn(CCR) 3}(Tp)L(PPh 3) ( 18, 19) and Ru[Sn(CCR) 3}(Cp)[P(OEt) 3](PPh 3) ( 20b) (R = Ph, p-tolyl) were also prepared from the reaction of trichlorostannyl complexes 1, 2, 5, and 6with Li +(CCR) −in thf. The complexes were characterized by spectroscopy and by X-ray crystal structure determination of Ru(SnClMe 2)(Cp)[P(OEt) 3](PPh 3) ( 15b). [ABSTRACT FROM AUTHOR]

Azide complexes [M(RN3)(CO)3P2]BPh41–3[M = Mn, Re; R = C6H5CH2, 4-CH3C6H4CH2, C6H5, 4-CH3C6H4, C5H9; P = PPh(OEt)2, PPh2(OEt)] were prepared by allowing tricarbonyl MH(CO)3P2 hydride complexes to react first with Brønsted acid (HBF4, CF3SO3H) and then with organic azide in the dark. In sunlight the reaction yielded tetraazabutadiene [M(η2-1,4-R2N4)(CO)2P2]BPh44–6 complexes or, with benzyl azide, imine [M{η1-NH=C(H)Ar}(CO)3P2]BPh47(Ar = C6H5, 4-CH3C6H4) derivatives. Tetraazabutadiene [M(η2-1,4-R2N4)(CO)2P2]BPh4 complexes were also prepared by reacting dicarbonyl MH(CO)2P3 species first with Brønsted acid and then with an excess of organic azide. Complexes were characterised spectroscopically (IR, 1H, 31P, 13C, 15N NMR data) and by the X-ray crystal structure determination of complex [Re{η2-1,4-(C6H5CH2)2N4}(CO)2{PPh(OEt)2}2]BPh4(5a). Strong evidence for coordination of the organic azide was obtained from the 15N NMR spectra of labelled [M(C6H5CH215NN15N)(CO)3P2]BPh4 derivatives. [ABSTRACT FROM AUTHOR]