Guanine crystal formation by bacteria.

BACKGROUND: Guanine crystals are organic biogenic crystals found in many organisms. Due to their exceptionally high refractive index, they contribute to structural color and are responsible for the reflective effect in the skin and visual organs in animals such as fish, reptiles, and spiders. Occurrence of these crystals in animals has been known for many years, and they have also been observed in eukaryotic microorganisms, but not in prokaryotes. RESULTS: In this work, we report the discovery of extracellular crystals formed by bacteria and reveal that they are composed of guanine monohydrate. This composition differs from that of biogenic guanine crystals found in other organisms, mostly composed of ß anhydrous guanine. We demonstrate the formation of these crystals by Aeromonas and other bacteria and investigate the metabolic traits related to their synthesis. In all cases studied, the presence of the bacterial guanine crystals correlates with the absence of guanine deaminase, which could lead to guanine accumulation providing the substrate for crystal formation. CONCLUSIONS: Our finding of the hitherto unknown guanine crystal occurrence in prokaryotes extends the range of organisms that produce these crystals to a new domain of life. Bacteria constitute a novel and more accessible model to study the process of guanine crystal formation and assembly. This discovery opens countless chemical and biological questions, including those about the functional and adaptive significance of their production in these microorganisms. It also paves the road for the development of simple and convenient processes to obtain biogenic guanine crystals for diverse applications.

Phenylalanine-Based Co2+ and Cd2+ 1D Coordination Polymers: Structural Properties and Catalytic Application for Solvent-Free Aerobic Oxidation of Cycloalkene.

Two 1D coordination polymers (CPs) with general formula [M(L)(H2O)(AcO)]n, (M = Co (1) or Cd (2), AcO = acetate anion and L denotes l-phenylalanine based ligand), were synthesized and fully characterized by various spectroscopies (UV-vis, FTIR, and NMR), thermal techniques, magnetic measurements (for 1), and single-crystal and powder X-ray diffraction studies. They can be described as "ribbon-like" 1D polymers constructed through a zigzag arrangement. The polymeric structure is developed due to the coordination mode adopted by the amino acid ligand, classified as µ3-N1O1:O1:O2, which simultaneously links three metal centers. This moiety also plays an important role as a magnetic coupler between metal centers in the cobalt system, which shows a weak antiferromagnetic interaction. Both CPs have also been used in the catalytic oxidation of cyclohexene with molecular oxygen (O2) as an oxidant. Under mild conditions, both compounds demonstrated remarkable catalytic activity, with the cobalt system being more efficient than the cadmium analogue (conversion: 73 and 58% and selectivity for the major product, 2-cyclohexanone: 63 and 55%, for 1 and 2, respectively). Leaching experiments and the results obtained using a radical quencher are consistent with a radical-mediated mechanism for the Co compound. The presence of the superoxide radical was also confirmed using EPR spectroscopy and DMPO as a spin trap, which was further validated by DFT calculations. The activity observed for the Cd analogue is attributed to the organic scaffold assisted by the templating effect of the metal ion.

Selenium-containing analogues of WC-9 are extremely potent inhibitors of Trypanosoma cruzi proliferation.

The obligate intracellular parasite, Trypanosoma cruzi is the etiologic agent of Chagas disease or American trypanosomiasis, which is the most prevalent parasitic disease in the Americas. The present chemotherapy to control this illness is still deficient particularly in the chronic stage of the disease. The ergosterol biosynthesis pathway has received much attention as a molecular target for the development of new drugs for Chagas disease. Especially, inhibitors of the enzymatic activity of squalene synthase were shown to be effective compounds on T. cruzi proliferation in in vitro assays. In the present study we designed, synthesized and evaluated the effect of a number of isosteric analogues of WC-9 (4-phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, on T. cruzi growth in tissue culture cells. The selenium-containing derivatives turned out to be extremely potent inhibitors of T. cruzi growth. Certainly, 3-phenoxyphenoxyethyl, 4-phenoxyphenoxyethyl, 4-(3-fluorophenoxy)phenoxyethyl, 3-(3-fluorophenoxy)phenoxyethyl selenocyanates and (±)-5-phenoxy-2-(selenocyanatomethyl)-2,3-dihydrobenzofuran arose as relevant members of this family of compounds, which exhibited effective ED50 values of 0.084 µM, 0.11 µM, 0.083, µM, 0.085, and 0.075 µM, respectively. The results indicate that compounds bearing the selenocyanate moiety are at least two orders of magnitude more potent than the corresponding skeleton counterpart bearing the thiocyanate group. Surprisingly, these compounds exhibited excellent selectively index values ranging from 900 to 1800 making these molecules promising candidates as antiparasitic agents.

A racemic and enantiopure unsymmetric diiron(III) complex with a chiral o-carborane-based pyridylalcohol ligand: combined chiroptical, magnetic, and nonlinear optical properties.

The design of molecule-based systems combining magnetic, chiroptical and second-order optical nonlinear properties is still very rare. We report an unusually unsymmetric diiron(III) complex 1, in which three bulky chiral carboranylpyridinealkoxide ligands (oCBhmp(-)) bridge both metal ions and the complex shows the above-mentioned properties. The introduction of o-carborane into the 2-(hydroxymethyl)pyridine (hmpH) architecture significantly alters the coordination of the simple or aryl-substituted 2-hmpH. The unusual architecture observed in 1 seems to be triggered by the poor nucleophilicity of our alkoxide ligand (oCBhmp(-)). A very rare case of spontaneous resolution takes place on precipitation or exposure to solvent vapor for the bulk compound, as confirmed by a combination of single-crystal and powder X-ray diffraction, second-harmonic generation, and circular dichroism. The corresponding enantiopure complexes (+)1 and (-)1 have also been synthesized and fully characterized. This research provides a new building block with unique geometry and electronics to construct coordination complexes with multifunctional properties.

Mebendazolium mesylate anhydride salt: rational design based on supramolecular assembly, synthesis, and solid-state characterization.

The design mebendazole (MBZ) multicomponent systems is important to obtain new materials that incorporate the API (active pharmaceutical ingredient) with better thermal stability, avoiding the interconversion of desmotropes. Interestingly, the presence of water molecules in the mebendazolium mesylate monohydrate prevents the formation of the R22(8) supramolecular synthon, found in all mebendazolium salts with polyatomic counterions. Here, we designed a new mebendazolium mesylate anhydrous salt based on statistical scrutiny of all mebendazole crystal structures identified in the literature and an exhaustive analysis of the conformational and geometrical requirements for the supramolecular assembly. The synthesis of this new salt and its solid-state characterization through single-crystal X-ray diffraction and complementary techniques are presented. As expected, mebendazole recrystallization in methanol with methanesulfonic acid - a Food and Drug Administration accepted coformer - in the absence of water yields a mesylate anhydrous salt with 1 : 1 stoichiometry. This new salt crystallizes in the P212121 (19) space group. The main intermolecular interactions found in the crystal structure are the hydrogen bonds that form a R22(8) supramolecular motif that assembles the ionic pairs. Additional non-classical H-bond, as well as π⋯π and carbonyl⋯cation interactions, contribute to the final stabilization of the crystal packing. This new salt is stable up to 205 °C when it undergoes the endothermic loss of the ester moiety to yield 2-amino-5-benzoylbenzimidazole. Moreover, preliminary dissolution experiments in aqueous 0.1 mol L-1 HCl suggest an apparent solubility of mebendazolium mesylate anhydride 2.67 times higher than that of the preferred for pharmaceutical formulations MBZ form C.

Structural insight into halide-coordinated [Fe4S4XnY4-n]2- clusters (X, Y = Cl, Br, I) by XRD and Mössbauer spectroscopy.

Iron sulphur halide clusters [Fe4S4Br4]2- and [Fe4S4X2Y2]2- (X, Y = Cl, Br, I) were obtained in excellent yields (77 to 78%) and purity from [Fe(CO)5], elemental sulphur, I2 and benzyltrimethylammonium (BTMA+) iodide, bromide and chloride. Single crystals of (BTMA)2[Fe4S4Br4] (1), (BTMA)2[Fe4S4Br2Cl2] (2), (BTMA)2[Fe4S4Cl2I2] (3), and (BTMA)2[Fe4S4Br2I2] (4) were isostructural to the previously reported (BTMA)2[Fe4S4I4] (5) (monoclinic, Cc). Instead of the chloride cubane cluster [Fe4S4Cl4]2-, we found the prismane-shaped cluster (BTMA)3[Fe6S6Cl6] (6) (P1̄). 57Fe Mössbauer spectroscopy indicates complete delocalisation with Fe2.5+ oxidation states for all iron atoms. Magnetic measurements showed small χMT values at 298 K ranging from 1.12 to 1.54 cm3 K mol-1, indicating the dominant antiferromagnetic exchange interactions. With decreasing temperature, the χMT values decreased to reach a plateau at around 100 K. From about 20 K, the values drop significantly. Fitting the data in the Heisenberg-Dirac-van Vleck (HDvV) as well as the Heisenberg Double Exchange (HDE) formalism confirmed the delocalisation and antiferromagnetic coupling assumed from Mössbauer spectroscopy.

Synthesis, structural and electrochemical properties of a new family of amino-acid-based coordination complexes.

Metalloproteins involved in oxidation-reduction processes in metabolism are fundamental for the wellbeing of every organism. The use of amino-acid-based compounds as ligands for the construction of biomimetic coordination systems represents a promising alternative for the development of new catalysts. Herein is presented a new family of copper, zinc and nickel coordination compounds, which show four-, five- and six- coordination geometries, synthesized using Schiff base ligands obtained from the amino acids L-alanine and L-phenylalanine. Structural analysis and property studies were performed using single-crystal X-ray diffraction data, spectroscopic and electrochemical experiments and DFT calculations. The analysis of the molecular and supramolecular architectures showed that the non-covalent interactions developed in the systems, together with the identity of the metal and the amino acid backbone, are determinants for the formation of the complexes and the stabilization of the resultant geometries. The CuII complexes were tested as candidates for the electrochemical conversion reduction of nitrite to NO, finding that the five-coordinate L-phenylalanine complex is the most suitable. Finally, some insights into the rational design of ligands for the construction of biomimetic complexes are suggested.

Tetrachlorocarbonyliridates: water-soluble carbon monoxide releasing molecules rate-modulated by the sixth ligand.

A new family of compounds is presented as potential carbon monoxide releasing molecules (CORMs). These compounds, based on tetrachlorocarbonyliridate(III) derivatives, were synthesized and fully characterized by X-ray diffraction, electrospray mass spectrometry, IR, NMR, and density functional theory calculations. The rate of CO release was studied via the myoglobin assay. The results showed that the rate depends on the nature of the sixth ligand, trans to CO, and that a significant modulation on the release rate can be produced by changing the ligand. The reported compounds are soluble in aqueous media, and the rates of CO release are comparable with those for known CORMs, releasing CO at a rate of 0.03-0.58 µM min(-1) in a 10 µM solution of myoglobin and 10 µM of the complexes.

Revisiting the absolute chirality and polymorphism of (-)-Istanbulin A.

The terpenoid (-)-Istanbulin A is a natural product isolated from Senecio filaginoides DC, one of the 270 species of Senecio (Asteraceae) which occurs in Argentina. The structure and absolute configuration of this compound [9a-hydroxy-3,4a,5-trimethyl-4a,6,7,8a,9,9a-hexahydro-4H,5H-naphtho[2,3-b]-furan-2,8-dione or (4S,5R,8R,10S)-1-oxo-8ß-hydroxy-10ßH-eremophil-7(11)-en-12,8ß-olide, C15H20O4] were determined by single-crystal X-ray diffraction studies. It proved to be a sesquiterpene lactone showing an eremophilanolide skeleton whose chirality is described as 4S,5R,8R,10S. Structural results were also in agreement with the one- and two-dimensional (1D and 2D) NMR and HR-ESI-MS data, and other complementary spectroscopic information. In addition, (-)-Istanbulin A is a polymorph of the previously reported form of (-)-Istanbulin A, form I; thus, the title compound is denoted form II or polymorph II. Structural data and a literature search allowed the chirality of Istanbulin A to be revisited. The antimicrobial and antifungal activities of (-)-Istanbulin A, form II, were evaluated in order to establish a reference for future comparisons and applications related to specific crystal forms of Istanbulins.

Nickel(II) complexes based on L-amino-acid-derived ligands: synthesis, characterization and study of the role of the supramolecular structure in carbon dioxide capture.

The formation of the symmetrical µ3-carbonate-bridged self-assembled trinuclear NiII complex Na2{[Ni(LO)2(H2O)]3(µ3-CO3)} (LO is the carboxylate anion of a L-tyrosine derivative), involves atmospheric CO2 uptake. The asymmetric unit of the complex comprises an octahedral coordination for the NiII with two L-tyrosine-based ligands, a water molecule and one O atom of the carbonate bridge. The Ni3-µ3-CO3 core in this compound is the first reported of this kind according to the Cambridge Structural Database (CSD). The supramolecular structure is mainly sustained by hydrogen bonds developed by the phenolic functionality of the L-tyrosine moiety of one ligand and the carboxylate group of a neighbouring ligand. The crystal packing is then characterized by three interpenetrated supramolecular helices associated with a diastereoisomer of the type R-supP, which is essential for the assembly process. Magnetic susceptibility and magnetization data support weak ferromagnetic exchange interactions within the novel Ni3-µ3-CO3 core. The NiII complex obtained under the same synthetic conditions but using the analogous ligand derived from the amino acid L-phenylalanine instead of L-tyrosine gives rise to to a mononuclear octahedral system. The results obtained for the different complexes demonstrate the role of the supramolecular structure regarding the CO2 uptake property for these NiII-amino-acid-based systems.

Synthesis, crystal structure and study of the crystal packing in the complex bis(4-aminopyridine-κN1)dichloridocobalt(II).

Despite the large number of reported crystalline structures of coordination complexes bearing pyridines as ligands, the relevance of π-π interactions among these hereroaromatic systems in the stabilization of their supramolecular structures and properties is not very well documented in the recent literature. The title compound, [CoCl2(C5H6N2)2], was obtained as bright-blue crystals suitable for single-crystal X-ray diffraction analysis from the reaction of 4-aminopyridine with cobalt(II) chloride in ethanol. The new complex was fully characterized by a variety of spectroscopic techniques and single-crystal X-ray diffraction. The crystal structure showed a tetrahedral complex stabilized mainly by bidimensional motifs constructed by π-π interactions with large horizontal displacements between the 4-aminopyridine units, and N-H...Cl hydrogen bonds. Other short contacts, such as C-H...Cl interactions, complete the three-dimensional arrangement. The supramolecular investigation was extended by statistical studies using the Cambridge Structural Database and a Hirshfeld surface analysis.

Performing organic chemistry with inorganic compounds: electrophilic reactivity of selected nitrosyl complexes.

The inorganic nitrosyl (NO(+)) complexes [Fe(CN) 5NO](2-), [Ru(bpy)2(NO)Cl](2+), and [IrCl 5(NO)](-) are useful reagents for the nitrosation of a variety of organic compounds, ranging from amines to the relatively inert alkenes. Regarding [IrCl 5(NO)](-), its high electrophilicity and inertness define it as a unique reagent and provide a powerful synthetic route for the isolation and stabilization of coordinated nitroso compounds that are unstable in free form, such as S-nitrosothiols and primary nitrosamines. Related to the high electrophilicity of [IrCl 5(NO)](-), an unusual behavior is described for its PPh 4(+) salt in the solid state, showing an electronic distribution represented by Ir(IV)-NO(*) instead of Ir (III)-NO(+) (as for the K(+) and Na(+) salts).

Electrospray ionization mass spectrometry of a novel family of complexes in which various nitroso compounds are stabilized via coordination to [IrCl5]2-.

Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS/MS) data of a unique family of complexes of nitroso compounds coordinated to pentachloroiridate(III), [Cl5IrN(O)XR]2- (X=NH, S, CH and R=alkyl, aryl) are presented. These novel complexes are obtained by nucleophilic attack of primary amines, thiols. and alkenes to the coordinated nitrosyl. Despite their lability and low volatility, MS analysis of complexes of the type MN(O)X was done for the first time, complementing other spectroscopic techniques. The intrinsic dissociation chemistry of the gaseous diagnostic ions was studied via ESI-MS/MS and found to be very useful to confirm the proposed connectivities of the parent complexes. In particular, ESI-MS of their solutions allows the detection of series of diagnostic ions, mainly, [M-Cl]-, [M+K]-, [M-NO]-*, and [M-Cl+AcN]- (AcN=acetonitrile), which confirmed the identity of the analyzed complexes to be M=[Cl5IrN(O)XR]2-. Major fragments were formed by losses of NO or N(O)XR. ESI-MS and ESI-MS/MS measurements are therefore shown to be the proper techniques to complement the spectroscopic characterization of this important class of nitroso complexes. An interesting rearrangement that does not take place in solution was observed in the gaseous phase, and a plausible mechanism is discussed.

Electronic perturbation in a molecular nanowire of [IrCl5(NO)]- units.

The nitrosyl in [IrCl5(NO)]- is probably the most electrophilic known to date. This fact is reflected by its extremely high IR frequency in the solid state, electrochemical behavior, and remarkable reactivity in solution. PPh4[IrCl5(NO)] forms a crystal in which the [IrCl5(NO)]- anions are in a curious wire-like linear arrangement, in which the distance between the N--O moiety of one anion and the trans chloride of the upper one nearby is only 2.8 A. For the same complex [IrCl5(NO)]- but with a different counterion, Na[IrCl5(NO)], the anions are stacked one over the other in a side-by-side arrangement. In this case the electronic distribution can be depicted as the closed-shell electronic structure Ir III-NO+, as expected for any d(6) third-row transition metal complex. However, in PPh4[IrCl5(NO)] an unprecedented electronic perturbation takes place, probably due to NO*-Cl- acceptor-donor interactions among a large number of [IrCl5(NO)]- units, favoring a different electronic distribution, namely the open-shell electronic structure Ir IV-NO*. This conclusion is based on XANES experimental evidence, which demonstrates that the formal oxidation state for iridium in PPh4[IrCl5(NO)] is +4, as compared with +3 in K[IrCl5(NO)]. In agreement, solid-state DFT calculations show that the ground state for [IrCl5(NO)]- in the PPh4+ salt comprises an open-shell singlet with an electronic structure which encompasses half of the spin density mainly localized on a metal-centered orbital, and the other half on an NO-based orbital. The electronic perturbation could be seen as an electron promotion from a metal-chloride to a metal-NO orbital, due to the small HOMO-LUMO gap in PPh4[IrCl5(NO)]. This is probably induced by electrostatic interactions acting as a result of the closeness and wire-like spatial arrangement of the Ir metal centers, imposed by lattice forces due to pi-pi stacking interactions among the phenyl rings in PPh4+. Experimental and theoretical data indicate that in PPh4[IrCl5(NO)] the Ir-N-O moiety is partially bent and tilted.

Solvation and structure of LiAlH(4) in ethereal solvents.

The nature of the solute species present in ethereal solutions of LiAlH(4) is of crucial importance for understanding the mechanisms for the reduction of ketones and other functional groups by LiAlH(4). We have employed a combination of theoretical and experimental techniques to investigate the structure of LiAlH(4) in ethereal solutions. Using complexation agents, we measured the IR spectra of LiAlH(4) and AlH(4)(-) in tetrahydrofuran (THF). Hybrid quantum-classical (QM-MM) simulations have also been carried out to compute the IR spectra of associated and dissociated LiAlH(4) species and the free-energy profile for the dissociation process in solution. Our experimental estimate of the dissociation constant in THF is 0.021 +/- 0.002, while the predicted computational value corresponding to a model dimethyl ether solvent is 0.001. The free-energy profile shows only one minimum corresponding to a contact ion pair at a Li-Al separation distance of 3.0 A. These results are consistent with the fact that LiAlH(4) is essentially associated in ethereal solutions forming contact ion pairs.