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Infection from multidrug resistant bacteria has become a growing health concern worldwide, increasing the need for developing new antibacterial agents. Among the strategies that have been studied, biofilm inhibitors have acquired relevance as a potential source of drugs that could act as a complement for current and new antibacterial therapies. Based on the structure of 2-alkyl-3-hydroxy-4-quinolone and N -acylhomoserine lactone, molecules that act as mediators of quorum sensing and biofilm formation in Pseudomonas aeruginosa, we designed, prepared, and evaluated the biofilm inhibition properties of long chain amide derivatives of 2-amino-4-quinolone in Staphylococcus aureus and P. aeruginosa . All compounds had higher biofilm inhibition activity in P. aeruginosa than in S. aureus. Particularly, compounds with an alkyl chain of 12 carbons exhibited the highest inhibition of biofilm formation. Docking scores and molecular dynamics simulations of the complexes of the tested compounds within the active sites of proteins related to quorum sensing had good correlation with the experimental results, suggesting the diminution of biofilm formation induced by these compounds could be related to the inhibition of these proteins.

New zincocenes [ZnCp'(2)] (2-5) with substituted cyclopentadienyl ligands C(5)Me(4)H, C(5)Me(4)tBu, C(5)Me(4)SiMe(2)tBu and C(5)Me(4)SiMe(3), respectively, have been prepared by the reaction of ZnCl(2) with the appropriate Cp'-transfer reagent. For a comparative structural study, the known [Zn(C(5)H(4)SiMe(3))(2)] (1), has also been investigated, along with the mixed-ring zincocenes [Zn(C(5)Me(5))(C(5)Me(4)SiMe(3))] (6) and [Zn(C(5)Me(5))(C(5)H(4)SiMe(3))] (7), the last two obtained by conproportionation of [Zn(C(5)Me(5))(2)] with 5 or 1, as appropriate. All new compounds were characterised by NMR spectroscopy, and by X-ray methods, with the exception of 7, which yields a side-product (C) upon attempted crystallisation. Compounds 5 and 6 were also investigated by (13)C CPMAS NMR spectroscopy. Zincocenes 1 and 2 have infinite chain structures with bridging Cp' ligands, while 3 and 4 exhibit slipped-sandwich geometries. Compounds 5 and 6 have rigid, eta(5)/eta(1)(sigma) structures, in which the monohapto C(5)Me(4)SiMe(3) ligand is bound to zinc through the silyl-bearing carbon atom, forming a Zn--C bond of comparable strength to the Zn--Me bond in ZnMe(2). Zincocene 5 has dynamic behaviour in solution, but a rigid eta(5)/eta(1)(sigma) structure in the solid state, as revealed by (13)C CPMAS NMR studies, whereas for 6 the different nature of the Cp' ligands and of the ring substituents of the eta(1)-Cp' group (Me and SiMe(3)) have permitted observation for the first time of the rigid eta(5)/eta(1) solution structure. Iminoacyl compounds of composition [Zn(eta(5)-C(5)Me(4)R)(eta(1)-C(NXyl)C(5)Me(4)R)] resulting from the reactions of some of the above zincocenes and CNXyl (Xyl=2,6-dimethylphenylisocyanide) have also been obtained and characterised.

New mercury cyclopentadienyl complexes Hg(eta1-Cp')Cl have been prepared by the reaction of HgCl2 and the appropriate KCp' salts or by the transmetalation of HgCl2 with ZnCp'2 (Cp'=C5Me4H, 1; C5Me4But, 2; C5Me4SiMe3, 3; C5H4SiMe3, 4). By contrast, only the SiMe3-substituted bis(cyclopentadienyl) derivatives, Hg(C5Me4SiMe3)2 (5) and Hg(C5H4SiMe3)2 (6), can be isolated by the above synthetic procedures and the appropriate ratio of reagents or from HgCp'Cl and KCp'. Solution NMR studies reveal nonfluxional behavior of the SiMe3-substituted complexes 3, 5, and 6. X-ray studies of the solid-state structures show that the six compounds contain eta1-Cp' ligands, with linear or almost linear C-Hg-Cl or C-Hg-C coordination environments. The two HgCp'2 compounds, 5 and 6, have the expected insular structures, but the HgCp'Cl derivatives show supramolecular associations by means of weak secondary Hg...Cl interactions. Thus, the HgCp'Cl compounds 1, 3, and 4 form three different polymeric chain structures with typically two Hg...Cl interactions of 3.04-3.46 A per mercury. By contrast, 2 forms a tetramer, [Hg(C5Me4SiMe3)Cl]4, with a cubelike arrangement of four Hg and four Cl atoms. Density functional theory has been used to investigate the electronic structure of the compounds.

In the further development and understanding of heme-copper O2-reduction chemistry inspired by the active-site chemistry in cytochrome c oxidase, we describe a dioxygen adduct, [(F8TPP)FeIII-(O22-)-CuII(TMPA)](ClO4) (3), formed by addition of O2 to a 1:1 mixture of the porphyrinate-iron(II) complex (F8TPP)FeII (1a) {F8TPP = tetrakis(2,6-difluorophenyl)porphyrinate dianion} and the copper(I) complex [(TMPA)CuI(MeCN)](ClO4) (1b) {TMPA = tris(2-pyridylmethyl)amine}. Complex 3 forms in preference to heme-only or copper-only binuclear products, is remarkably stable {t1/2 (RT; MeCN) approximately 20 min; lambda max = 412 (Soret), 558 nm; EPR silent}, and is formulated as a peroxo complex on the basis of manometry {1a/1b/O2 = 1:1:1}, MALDI-TOF mass spectrometry {16O2, m/z 1239 [(3 + MeCN)+]; 18O2, m/z 1243}, and resonance Raman spectroscopy {nu(O-O) = 808 cm-1; Delta16O2/18O2 = 46 cm-1; Delta16O2/16/18O2 = 23 cm-1}. Consistent with a mu-eta2:eta1 bridging peroxide ligand, two metal-O stretching frequencies are observed {nu(Fe-O) = 533 cm-1, nu(Fe-O-Cu) = 511 cm-1}, and supporting normal coordinate analysis is presented. 2H and 19F NMR spectroscopies reveal that 3 is high-spin {also muB = 5.1 +/- 0.2, Evans method} with downfield-shifted pyrrole and upfield-shifted TMPA resonances, similar to the pattern observed for the structurally characterized mu-oxo complex [(F8TPP)FeIII-O-CuII(TMPA)]+ (4) (known S = 2 system, antiferromagnetically coupled high-spin FeIII and CuII). Mössbauer spectroscopy exhibits a sharp quadrupole doublet (zero field; delta = 0.57 mm/s, |DeltaEQ| = 1.14 mm/s) for 3, with isomer shift and magnetic field dependence data indicative of a peroxide ligand and S = 2 formulation. Both UV-visible-monitored stopped-flow kinetics and Mössbauer spectroscopic studies reveal the formation of heme-only superoxide complex (S)(F8TPP)FeIII-(O2-) (2a) (S = solvent molecule) prior to 3. Thermal decomposition of mu-peroxo complex 3 yields mu-oxo complex 4 with concomitant release of approximately 0.5 mol O2 per mol 3. Characterization of the reaction 1a/1b + O2 --> 2 --> 3 --> 4, presented here, advances our understanding and provides new insights to heme/Cu dioxygen-binding and reduction.

Square-planar ethylene rhodium derivatives bearing pincer diphosphite ligands have been prepared and characterized, they display a rare in-plane coordination which, based on DFT calculations, has been mainly attributed to steric effects.

While, in general, decamethylzincocene, Zn(C5Me5)2, and other zincocenes, Zn(C5Me4R)2 (R = H, But, SiMe3), react with dialkyl and diaryl derivatives, ZnR'2, to give the half-sandwich compounds (eta5-C5Me4R)ZnR', under certain conditions the reactions of Zn(C5Me5)2 with ZnEt2 or ZnPh2 produce unexpectedly the dizincocene Zn2(eta5-C5Me5)2 (1) in low yields, most likely as a result of the coupling of two (eta5-C5Me5)Zn* radicals. An improved, large scale (ca. 2 g) synthesis of 1 has been achieved by reduction of equimolar mixtures of Zn(C5Me5)2 and ZnCl2 with KH in tetrahydrofuran. The analogous reduction of Zn(C5Me4R)2 (R = H, SiMe3, But) yields only decomposition products, but the isotopically labeled dimetallocene 68Zn2(eta5-C5Me5)2 and the related compound Zn2(eta5-C5Me4Et)2 (2) have been obtained by this procedure. Compound 2 has lower thermal stability than 1, but it has been unequivocally characterized by low-temperature X-ray diffraction studies. As for 1 a combination of structural characterization techniques has provided unambiguous evidence for its formulation as the Zn-Zn bonded dimer Zn2(eta5-C5Me4Et)2, with a short Zn-Zn bond of 2.295(3) A indicative of a strong Zn-Zn bonding interaction. The electronic structure and the bonding properties of 1 and those of related dizincocenes Zn2(eta5-Cp')2 have been studied by DFT methods (B3LYP level), with computed bond distances and angles for dizincocene 1 very similar to the experimental values. The Zn-Zn bond is strong (ca. 62 kcal.mol-1 for 1) and resides in the HOMO-4, that has a contribution of Zn orbitals close to 60%, consisting mostly of the Zn 4s orbitals (more than 96%).

The geometric and electronic structure of the untethered heme-peroxo-copper model complex [(F(8)TPP)Fe(III)-(O(2)(2)(-))-Cu(II)(TMPA)](ClO(4)) (1) has been investigated using Cu and Fe K-edge EXAFS spectroscopy and density functional theory calculations in order to describe its geometric and electronic structure. The Fe and Cu K-edge EXAFS data were fit with a Cu...Fe distance of approximately 3.72 A. Spin-unrestricted DFT calculations for the S(T) = 2 spin state were performed on [(P)Fe(III)-(O(2)(2)(-))-Cu(II)(TMPA)](+) as a model of 1. The peroxo unit is bound end-on to the copper, and side-on to the high-spin iron, for an overall mu-eta(1):eta(2) coordination mode. The calculated Cu...Fe distance is approximately 0.3 A longer than that observed experimentally. Reoptimization of [(P)Fe(III)-(O(2)(2)(-))-Cu(II)(TMPA)](+) with a 3.7 A Cu...Fe constrained distance results in a similar energy and structure that retains the overall mu-eta(1):eta(2)-peroxo coordination mode. The primary bonding interaction between the copper and the peroxide involves electron donation into the half-occupied Cu d(z)2 orbital from the peroxide pi(sigma) orbital. In the case of the Fe(III)-peroxide eta(2) bond, the two major components arise from the donor interactions of the peroxide pi*(sigma) and pi*(v) orbitals with the Fe d(xz) and d(xy) orbitals, which give rise to sigma and delta bonds, respectively. The pi*(sigma) interaction with both the half-occupied d(z)2 orbital on the copper (eta(1)) and the d(xz) orbital on the iron (eta(2)), provides an effective superexchange pathway for strong antiferromagnetic coupling between the metal centers.

Whereas the reaction of the anionic palladium metallacycle [K[Pd(CH2CMe2-o-C6H4)(kappa2-Tp)]] with CH2Cl2 leads to the isolation of the stable Pd(IV) chloromethyl complex [Pd(CH2CMe2-o-C6H4)(kappa3-Tp)(CH2Cl)], the analogous reactions with CH2Br2 and CH2I2 give rise to the six membered metallacycles [Pd(CH2CMe2-o-C6H4(CH2))(kappa3-Tp)X](X = Br or I), as a result of the formal insertion of CH2 into the Pd-C(aryl) bond.

The beryllocenes [Be(C(5)Me(4)H)(2)] (1), [Be(C(5)Me(5))(2)] (2), and [Be(C(5)Me(5))(C(5)Me(4)H)] (3) have been prepared from BeCl(2) and the appropriate KCp' reagent in toluene/diethyl ether solvent mixtures. The synthesis of 1 is facile (20 degrees C, overnight), but generation of decamethylberyllocene 2 demands high temperatures (ca. 115 degrees C) and extended reaction times (3-4 days). The mixed-ring beryllocene 3 is obtained when the known [(eta(5)-C(5)Me(5))BeCl] is allowed to react with K[C(5)Me(4)H], once more under somewhat forcing conditions (115 degrees C, 36 h). The structures of the three metallocenes have been determined by low-temperature X-ray studies. Both 1 and 3 present eta5/eta1 geometries of the slip-sandwich type, whereas 2 exhibits an almost regular, ferrocene-like, sandwich structure. In the mixed-ring compound 3, C(5)Me(5) is centrally bound to beryllium and the eta(1)-C(5)Me(4)H ring bonds to the metal through the unique CH carbon atom. This is also the binding mode of the eta(1)-ring of 1. To analyze the nature of the bonding in these molecules, theoretical calculations at different levels of theory have been performed on compounds 2 and 3, and a comparison with the bonding in [Be(C(5)H(5))(2)] has been made. As for the latter molecule, energy differences between the eta5/eta5 and the eta5/eta1 structures of 2 are very small, being of the order of a few kcal mol(-1). Constrained space orbital variations (CSOV) calculations show that the covalent character in the bonding is larger for [Be(C(5)Me(5))(2)] than for [Be(C(5)H(5))(2)] due to larger charge delocalization and to increased polarizability of the C(5)Me(5) fragment.

Treatment of complex V(N-2,6-(i)Pr(2)C(6)H(3))Cl(3) with 1,2-dimethoxyethane (dme) gives in quasi-quantitative yield the adduct V(N-2,6-(i)Pr(2)C(6)H(3))Cl(3)(dme) (1). Interaction of 1 with bidentate phosphines gives V(N-2,6-(i)Pr(2)C(6)H(3))Cl(3)(P-P) (P-P = depe, 2a; dppe, 2b) compounds. An X-ray analysis (monoclinic, space group P2(1)/c, a = 14.7387(14) Å, b = 10.6738(10) Å, c = 16.999(3) Å, beta = 90.954(2) degrees, Z = 4, R = 0.0544), carried out on complex 2a, shows a mer arrangement of the chloride ligands and a nonsymmetrical coordination of the diphosphine ligand. One of the phosphorus atoms occupies the trans position with respect to the organoimido ligand. MO calculations on the models V(NR)Cl(3)(H(2)PCH(2)CH(2)PH(2)) (R = H, C(6)H(5)) of complex 2a were performed. The mer isomer, which is more stable than the fac isomer, shows good agreement with the experimental data.