Solid state physicochemical properties and applications of organic and metallo-organic fullerene derivatives

We review the fundamental properties and main applications of organic derivatives and complexes of fullerenes in the solid-state form. We address in particular the structural properties, in terms of crystal structure, polymorphism, orientational transitions and morphology, and the electronic structure and derived properties, such as chemical activity, electrical conduction mechanisms, optical properties, heat conduction and magnetism. The last two sections of the review focus on the solid-state optoelectronic and electrochemical applications of fullerene derivatives, which range from photovoltaic cells to field-effect transistors and photodetectors on one hand, to electron-beam resists, electrolytes and energy storage on the other.Peer ReviewedPreprin

Solution of an associating lattice gas model with density anomaly on a Husimi lattice

We study a model of a lattice gas with orientational degrees of freedom which resemble the formation of hydrogen bonds between the molecules. In this model, which is the simplified version of the Henriques-Barbosa model, no distinction is made between donors and acceptors in the bonding arms. We solve the model in the grand-canonical ensemble on a Husimi lattice built with hexagonal plaquettes with a central site. The ground-state of the model, which was originally defined on the triangular lattice, is exactly reproduced by the solution on this Husimi lattice. In the phase diagram, one gas and two liquid (high density-HDL and low density-LDL) phases are present. All phase transitions (GAS-LDL, GAS-HDL, and LDL-HDL) are discontinuous, and the three phases coexist at a triple point. A line of temperatures of maximum density (TMD) in the isobars is found in the metastable GAS phase, as well as another line of temperatures of minimum density (TmD) appears in the LDL phase, part of it in the stable region and another in the metastable region of this phase. These findings are at variance with simulational results for the same model on the triangular lattice, which suggested a phase diagram with two critical points. However, our results show very good quantitative agreement with the simulations, both for the coexistence loci and the densities of particles and of hydrogen bonds. We discuss the comparison of the simulations with our results.Comment: 12 pages, 5 figure

Ligand-guided homology modeling drives identification of novel histamine H3 receptor ligands

In this study, we report a ligand-guided homology modeling approach allowing the analysis of relevant binding site residue conformations and the identification of two novel histamine H3 receptor ligands with binding affinity in the nanomolar range. The newly developed method is based on exploiting an essential charge interaction characteristic for aminergic G-protein coupled receptors for ranking 3D receptor models appropriate for the discovery of novel compounds through virtual screening

Multi-heme Cytochromes in Shewanella oneidensis MR-1:Structures, functions and opportunities

Multi-heme cytochromes are employed by a range of microorganisms to transport electrons over distances of up to tens of nanometers. Perhaps the most spectacular utilization of these proteins is in the reduction of extracellular solid substrates, including electrodes and insoluble mineral oxides of Fe(III) and Mn(III/IV), by species of Shewanella and Geobacter. However, multi-heme cytochromes are found in numerous and phylogenetically diverse prokaryotes where they participate in electron transfer and redox catalysis that contributes to biogeochemical cycling of N, S and Fe on the global scale. These properties of multi-heme cytochromes have attracted much interest and contributed to advances in bioenergy applications and bioremediation of contaminated soils. Looking forward there are opportunities to engage multi-heme cytochromes for biological photovoltaic cells, microbial electrosynthesis and developing bespoke molecular devices. As a consequence it is timely to review our present understanding of these proteins and we do this here with a focus on the multitude of functionally diverse multi-heme cytochromes in Shewanella oneidensis MR-1. We draw on findings from experimental and computational approaches which ideally complement each other in the study of these systems: computational methods can interpret experimentally determined properties in terms of molecular structure to cast light on the relation between structure and function. We show how this synergy has contributed to our understanding of multi-heme cytochromes and can be expected to continue to do so for greater insight into natural processes and their informed exploitation in biotechnologies

A brief review of co-doping

AbstractDopants and defects are important in semiconductor and magnetic devices. Strategies for controlling doping and defects have been the focus of semiconductor physics research during the past decades and remain critical even today. Co-doping is a promising strategy that can be used for effectively tuning the dopant populations, electronic properties, and magnetic properties. It can enhance the solubility of dopants and improve the stability of desired defects. During the past 20 years, significant experimental and theoretical efforts have been devoted to studying the characteristics of co-doping. In this article, we first review the historical development of co-doping. Then, we review a variety of research performed on co-doping, based on the compensating nature of co-dopants. Finally, we review the effects of contamination and surfactants that can explain the general mechanisms of co-doping.</jats:p

Cytochrome c signalosome in mitochondria

Cytochrome c delicately tilts the balance between cell life (respiration) and cell death (apoptosis). Whereas cell life is governed by transient electron transfer interactions of cytochrome c inside the mitochondria, the cytoplasmic adducts of cytochrome c that lead to cell death are amazingly stable. Interestingly, the contacts of cytochrome c with its counterparts shift from the area surrounding the heme crevice for the redox complexes to the opposite molecule side when the electron flow is not necessary. The cytochrome c signalosome shows a higher level of regulation by post-translational modifications—nitration and phosphorylation—of the hemeprotein. Understanding protein interfaces, as well as protein modifications, would puzzle the mitochondrial cytochrome c-controlled pathways out and enable the design of novel drugs to silence the action of pro-survival and pro-apoptotic partners of cytochrome c.Spanish Ministry of Science and Innovation BFU2009-07190Andalusian Government BIO198 P08-CVI-387

How proteins bind macrocycles

The potential utility of synthetic macrocycles (MCs) as drugs, particularly against low-druggability targets such as protein-protein interactions, has been widely discussed. There is little information, however, to guide the design of MCs for good target protein-binding activity or bioavailability. To address this knowledge gap, we analyze the binding modes of a representative set of MC-protein complexes. The results, combined with consideration of the physicochemical properties of approved macrocyclic drugs, allow us to propose specific guidelines for the design of synthetic MC libraries with structural and physicochemical features likely to favor strong binding to protein targets as well as good bioavailability. We additionally provide evidence that large, natural product-derived MCs can bind targets that are not druggable by conventional, drug-like compounds, supporting the notion that natural product-inspired synthetic MCs can expand the number of proteins that are druggable by synthetic small molecules.R01 GM094551 - NIGMS NIH HHS; GM064700 - NIGMS NIH HHS; GM094551 - NIGMS NIH HHS; R01 GM064700 - NIGMS NIH HHS; GM094551-01S1 - NIGMS NIH HH

A new type of Na+-driven ATP synthase membrane rotor with a two-carboxylate ion-coupling motif

Abstract: The anaerobic bacterium Fusobacterium nucleatum uses glutamate decarboxylation to generate a transmembrane gradient of Na+. Here, we demonstrate that this ion-motive force is directly coupled to ATP synthesis, via an F1Fo-ATP synthase with a novel Na+ recognition motif, shared by other human pathogens. Molecular modeling and free-energy simulations of the rotary element of the enzyme, the c-ring, indicate Na+ specificity in physiological settings. Consistently, activity measurements showed Na+ stimulation of the enzyme, either membrane-embedded or isolated, and ATP synthesis was sensitive to the Na+ ionophore monensin. Furthermore, Na+ has a protective effect against inhibitors targeting the ion-binding sites, both in the complete ATP synthase and the isolated c-ring. Definitive evidence of Na+ coupling is provided by two identical crystal structures of the c11 ring, solved by X-ray crystallography at 2.2 and 2.6 Å resolution, at pH 5.3 and 8.7, respectively. Na+ ions occupy all binding sites, each coordinated by four amino acids and a water molecule. Intriguingly, two carboxylates instead of one mediate ion binding. Simulations and experiments demonstrate that this motif implies that a proton is concurrently bound to all sites, although Na+ alone drives the rotary mechanism. The structure thus reveals a new mode of ion coupling in ATP synthases and provides a basis for drug-design efforts against this opportunistic pathogen. Author Summary: Essential cellular processes such as biosynthesis, transport, and motility are sustained by the energy released in the hydrolysis of ATP, the universal energy carrier in living cells. Most ATP in the cell is produced by a membrane-bound enzyme, the ATP synthase, through a rotary mechanism that is coupled to the translocation of ions across the membrane. The majority of ATP synthases are energized by transmembrane electrochemical gradients of protons (proton-motive force), but a number of organisms, including some important human pathogens, use gradients of sodium ions instead (sodium-motive force). The ion specificity of ATP synthases is determined by a membrane-embedded sub-complex, the c-ring, which is the smallest known biological rotor. The functional mechanism of the rotor ring and its variations among different organisms are of wide interest, because of this enzyme's impact on metabolism and disease, and because of its potential for nanotechnology applications. Here, we characterize a previously unrecognized type of Na+-driven ATP synthase from the opportunistic human pathogen Fusobacterium nucleatum, which is implicated in periodontal diseases. We analyzed this ATP synthase and its rotor ring through a multi-disciplinary approach, combining cell-growth and biochemical assays, X-ray crystallography and computer-simulation methods. Two crystal structures of the membrane rotor were solved, at low and high pH, revealing an atypical ion-recognition motif mediated by two carboxylate side-chains. This motif is shared by other human pathogens, such as Mycobacterium tuberculosis or Streptococcus pneumonia, whose ATP synthases are targets of novel antibiotic drugs. The implications of this ion-recognition mode on the mechanism of the ATP synthase and the cellular bioenergetics of F. nucleatum were thus examined. Our results provide the basis for future pharmacological efforts against this important pathogen