Empirical Charge Scheme for Transition Metals and Lanthanoids: Development and Applications

Parameters for the fluctuating charge model are derived for In(III), La(III), Lu(III) and Bi(III), based on x-ray structural data and DFT single point calculations. A number of density partitioning schemes is tested

Redox Potentials of High‐Valent Iron‐, Cobalt‐, and Nickel‐Oxido Complexes: Evidence for Exchange Enhanced Reactivity

The ferrocene titration method has been employed to determine the one‐electron reduction potentials of a series of oxido‐iron(IV), oxido‐cobalt(IV) and oxido/hydroxido‐nickel(III) complexes based on the same tetradentate TMG3tren ligand (TMG3tren=tris[2‐(N‐tetramethylguanidyl)ethyl]amine). The S=2 ground state of the [(TMG3tren)FeIV=O]2+ complex allows an exchange enhanced reactivity, which enables it to perform efficient oxygen atom transfer (OAT) and hydrogen atom abstraction (HAA) reactions with a low one‐electron reduction potential of 270 mV vs. SCE. In the absence of exchange enhanced reactivity, the OAT and HAA abilities of the S=3/2 [(TMG3tren)CoIV−O(Sc(OTf)3)]2+, S=1/2 [(TMG3tren)NiIII−O(H)]2+ and the previously reported S=1 [(TMC)(CH3CN)FeIV=O]2+ and [(N4Py)FeIV=O]2+ complexes can be directly correlated to their reduction potentials. Notably, [(N4Py)FeIV=O]2+ and [(TMG3tren)FeIV=O]2+ exhibit similar OAT and HAA reactivities although the reduction potential of [(N4Py)FeIV=O]2+ is 0.24 V more positive than that of [(TMG3tren)FeIV=O]2+. The present study therefore provides experimental evidence for exchange enhanced reactivity and rationalizes nature's choice for employing S=2 oxido‐iron(IV) cores to achieve difficult oxidation reactions at biologically viable potentials.Heidelberg UniversityDeutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Peer Reviewe

Cyclic peptide marine metabolites and CuII

Cyclic pseudo-peptides derived from marine metabolites of the genus Lissoclinum bistratum and Lissoclinum patella have attracted scientific interest in the last two decades. Their structural properties and solution dynamics have been analyzed in detail, elaborate synthetic procedures for the natural products and synthetic derivatives developed, the biosynthetic pathways studied and it now is possible to produce them biosynthetically. Initially, these macrocyclic ligands were studied due to their medicinal and pharmaceutical potential-some of the isolated cyclic pseudo-peptides show high cytotoxic and antiviral activity. A major focus in the last decade has been on their Cu coordination chemistry, as a number of studies have indicated that dinuclear Cu complexes of cyclic peptides may be involved in the ascidians' metabolism, and this is the focus of the present review

Molecular shape

Molecular shape is recognized as an emergent property that complements the projection fromfour-dimensional space-time to tangent Euclidean space. Projection from hypercomplex algebra to real algebra necessitates the three-dimensional definition of concepts such as chirality, quantum uncertainty and probability density to compensate for errors of abstraction. The emergent alternative description of extranuclear charge density as spherical standing waves, optimized by a golden spiral, reveals atomic structure in line with the periodic table of the elements and underpinning the concepts of bond order, interatomic distance and stretching force constant, related to chemical interaction. The principles giving rise to molecular structure are shown to depend, like bond order, on the constructive interference of atomic wave fields, optimized by minimal adjustment to bond orders. The procedure is shown to be equivalent to the philosophy of molecular mechanics. Arguments based on the traditional interpretation of electronegativity, are presented to relate the parameters of strain-free bond lengths, dissociation energies and harmonic force constants, used in molecular mechanics, to quantum-mechanically defined ionization radii of atoms. Atomic electron densities and a bond-order function, both obtained by number-theory optimization, enable the direct calculation of interatomic distance, dissociation energy and stretching force constant for all pairwise interactions of any order. Torsional interaction determines the final shape of a molecule and presumably can only be understood as a four-dimensional effect.http://www.springer.com/series/430hj201

Carbonic anhydrase activity of dinuclear CuII complexes with patellamide model ligands

The dicopper(ii) complexes of six pseudo-octapeptides, synthetic analogues of ascidiacyclamide and the patellamides, found in ascidians of the Pacific and Indian Oceans, are shown to be efficient carbonic anhydrase model complexes with k up to 7.3 × 10 s (uncatalyzed: 3.7 × 10 s; enzyme-catalyzed: 2 × 10 -1.4 × 10 s) and a turnover number (TON) of at least 1700, limited only by the experimental conditions used. So far, no copper-based natural carbonic anhydrases are known, no faster model systems have been described and the biological role of the patellamide macrocycles is so far unknown. The observed CO hydration rates depend on the configuration of the isopropyl side chains of the pseudo-octapeptide scaffold, and the naturally observed R*,S*, R*,S* geometry is shown to lead to more efficient catalysts than the S*,S*,S*,S* isomers. The catalytic efficiency also depends on the heterocyclic donor groups of the pseudo-octapeptides. Interestingly, the dicopper(ii) complex of the ligand with four imidazole groups is a more efficient catalyst than that of the close analogue of ascidiacyclamide with two thiazole and two oxazoline rings. The experimental observations indicate that the nucleophilic attack of a Cu- coordinated hydroxide at the CO carbon center is rate determining, i.e. formation of the catalyst-CO adduct and release of carbonate/bicarbonate are relatively fast processes

Insights into the Electronic Structure of CuII Bound to an Imidazole Analogue of Westiellamide.

Three synthetic analogues of westiallamide, HL, have previously been synthesized (HL) that have a common backbone (derived from l-valine) with HL but differ in their heterocyclic rings (imidazole, oxazole, thiazole, and oxazoline). Herein we explore in detail through high-resolution pulsed electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) spectroscopy in conjunction with density functional theory (DFT) the geometric and electronic structures of the mono- and dinuclear Cu complexes of these cyclic pseudo hexapeptides. Orientation-selective hyperfine sublevel correlation, electron nuclear double resonance, and three-pulse electron spin echo envelope modulation spectroscopy of [Cu(HL)(MeOH)] reveal delocalization of the unpaired electron spin onto the ligating and distal nitrogens of the coordinated heterocyclic rings and that they are magnetically inequivalent. DFT calculations confirm this and show similar spin densities on the distal heteroatoms in the heterocyclic rings coordinated to the Cu ion in the other cyclic pseudo hexapeptide [Cu(HL)(MeOH)] complexes. The magnetic inequivalencies in [Cu(HL)(MeOH)] arise from different orientations of the heterocyclic rings coordinated to the Cu ion, and the delocalization of the unpaired electron onto the distal heteroatoms within these N-methylimidazole rings depends upon their location with respect to the Cu dx-y orbital. A systematic study of DFT functionals and basis sets was undertaken to examine the ability to reproduce the experimentally determined spin Hamiltonian parameters. Inclusion of spin-orbit coupling (SOC) using MAG-ReSpect or ORCA with a BHLYP/IGLO-II Wachters setup with SOC corrections and ∼38% Hartree-Fock exchange gave the best predictions of the g and A(Cu) matrices. DFT calculations of the N hyperfine and quadrupole parameters for the distal nitrogens of the coordinated heterocyclic rings in [Cu(HL)(MeOH)] with the B1LYP functional and the SVP basis set were in excellent agreement with the experimental data, though other choices of functional and basis set also provided reasonable values. MCD, EPR, mass spectrometry, and DFT showed that preparation of the dinuclear Cu complex in a 1:1 MeOH/glycerol mixture (necessary for MCD) resulted in the exchange of the bridging methoxide ligand for glycerol with a corresponding decrease in the magnitude of the exchange coupling

Copper(II) complexes with aromatic nitrogen-containing heterocycles as effective inhibitors of quorum sensing activity in Pseudomonas aeruginosa

Five copper(II) complexes 1-5 with aromatic nitrogen-containing heterocycles, pyrimidine (pm, 1), pyrazine (pz, 2), quinazoline (qz, 3 and 4) and phthalazine (phtz, 5) have been synthesized and structurally characterized by spectroscopic and single-crystal X-ray diffraction techniques. The crystallographic results show that, dependent on the ligand structure, complexes 1-5 are of different nuclearity. The antimicrobial efficiency of complexes 1-5 has been evaluated against three clinically relevant microorganisms and none of the complexes showed significant growth inhibiting activity, with values of minimum inhibitory concentrations (MIC) in the mM range. Since in many bacteria, pathogenicity and virulence are regulated by intercellular communication processes, quorum sensing (QS), the effect of the copper(II) complexes on bacterial QS has also been examined. The results indicate that the investigated complexes inhibit violacein production in Chromobacterium violaceum CV026, suggesting an anti-QS activity. In order to differentiate, which of the QS pathways was affected by the copper(II) complexes, three biosensor strains were used: the PAO1 Delta rhlIpKD-rhlA and the PA14-R3 Delta lasIPrsaI lux strain to directly measure the levels of C4-HSL (N-butanoyl-homoserine lactone) and 3OC12-HSL (N-3-oxo-dodecanoyl- homoserine lactone), respectively, and PAO1 Delta pqsA mini-CTX luxPpqsA for the detection of AHQs (2-alkyl-4-quinolones). Complexes 1-5 were shown to be efficient inhibitors of biofilm formation of the human opportunistic pathogen Pseudomonas aeruginosa PAO1, with the qz-containing complex 3 being the most active. Finally, the most anti-QS-active complexes 1 and 3 showed synergistic activity against a multi-drug resistant clinical isolate of P. aeruginosa, when supplied in combination with the known antibiotics piperacillin and ceftazidime

Ferro- and antiferromagnetic coupling in a chlorido-bridged, tetranuclear Cu(ii) complex

International audienceA bispidine-like ligand involving four pyridine-N and three aliphatic-N donor atoms forms a bimetallic species with CuCl2 in which all seven N-donors are bound and which aggregates in the crystal through double chloride-bridging to give a tetranuclear unit. The magnetism of this solid can be interpreted in terms of a relatively weak antiferromagnetic coupling between the two Cu(ii) centres of the dinuclear subunits and a strong ferromagnetic coupling of the Cu(ii) centres in different dinuclear units involved in the bis-chlorido bridge. In solution, the assembly decays into the dinuclear subunits and, in agreement with the solid state studies, the interaction between the corresponding CuII centres is shown to be primarily due to dipole-dipole coupling

Silver(I) complexes with phthalazine and quinazoline as effective agents against pathogenic Pseudomonas aeruginosa strains

Five silver(I) complexes with aromatic nitrogen-containing heterocycles, phthalazine (phtz) and quinazoline (qz), were synthesized, characterized and analyzed by single-crystal X-ray diffraction analysis. Although different AgX salts reacted with phtz, only dinuclear silver(I) complexes of the general formula {[Ag(X-O)(phtz-N)](2)(mu-phtz-N,N')(2)} were formed, X = NO3- (1), CF3SO3- (2) and ClO4- (3). However, reactions of qz with an equimolar amount of AgCF3SO3 and AgBF4 resulted in the formation of polynuclear complexes, {[Ag(CF3SO3-O)(qz-N)](2)}(n) (4) and {[Ag(qz-N)][BF4]}(n) (5). Complexes 1-5 were evaluated by in vitro antimicrobial studies against a panel of microbial strains that lead to many skin and soft tissue, respiratory, wound and nosocomial infections. The obtained results indicate that all tested silver(I) complexes have good antibacterial activity with MIC (minimum inhibitory concentration) values in the range from 2.9 to 48.0 mu M against the investigated strains. Among the investigated strains, these complexes were particularly efficient against pathogenic Pseudomonas aeruginosa (MIC = 2.9-29 mu M) and had a marked ability to disrupt clinically relevant biofilms of strains with high inherent resistance to antibiotics. On the other hand, their activity against the fungus Candida albicans was moderate. In order to determine the therapeutic potential of silver(I) complexes 1-5, their antiproliferative effect on the human lung fibroblastic cell line MRC5, has been also evaluated. The binding of complexes 1-5 to the genomic DNA of P. aeruginosa was demonstrated by gel electrophoresis techniques and well supported by molecular docking into the DNA minor groove. All investigated complexes showed an improved cytotoxicity profile in comparison to the clinically used AgNO3.This is the peer reviewed version of the paper: Glisić, B., Šenerović, L., Comba, P., Wadepohl, H., Veselinović, A., Milivojević, D., Djuran, M. I.,& Nikodinović-Runić, J.. (2016). Silver(I) complexes with phthalazine and quinazoline as effective agents against pathogenic Pseudomonas aeruginosa strains. in Journal of Inorganic Biochemistry Elsevier Science Inc, New York., 155, 115-128. [https://doi.org/10.1016/j.jinorgbio.2015.11.026