Microwave-Assisted Synthesis of Organometallic Rhenium (I) Pentylcarbonato Complexes: New Synthon for Carboxylato, Sulfonato and Chlorido Complexes.

Tricarbonylrhenium(I)(α-diimine) complexes are of importance because of their strong cytotoxic and fluorescence properties. Syntheses of such complexes were achieved through a two-step process. First, the pentylcarbonato complexes, fac-(CO)3(α-diimine)ReOC(O)OC5H11 were synthesized through a microwave-assisted reaction of Re2(CO)10, α-diimine, 1-pentanol and CO2 in a few hours. Second, the pentylcarbonato complexes are treated with carboxylic, sulfonic and halo acids to obtain the corresponding carboxylato, sulfonato and halido complexes. This is the first example of conversion of Re2(CO)10 into a rhenium carbonyl complex through microwave-assisted reaction.

Unprecedented anticancer activities of organorhenium sulfonato and carboxylato complexes against hormone-dependent MCF-7 and hormone-independent triple-negative MDA-MB-231 breast cancer cells.

Cisplatin and other metal-based drugs often display side effects and tumor resistance after prolonged use. Because rhenium-based anticancer complexes are often less toxic, a novel series of organorhenium complexes were synthesized of the types: XRe(CO)3Z (X = α-diimines and Z = p-toluenesulfonate, 1-naphthalenesulfonate, 2-naphthalenesulfonate, picolinate, nicotinate, aspirinate, naproxenate, flufenamate, ibuprofenate, mefenamate, tolfenamate, N-acetyl-tryptophanate), and their biological properties were examined. Specifically, in hormone-dependent MCF-7 and hormone-independent triple-negative MDA-MB-231 breast cancer cells, the p-toluenesulfonato, 1-naphthalenesulfonato, 2-naphthalenesulfonato, picolinato, nicotinato, acetylsalicylato, flufenamato, ibuprofenato, mefenamato, and N-acetyl-tryptophanato complexes were found to be far more potent than conventional drug cisplatin. DNA-binding studies were performed in each case via UV-Vis titrations, cyclic voltammetry, gel electrophoresis, and viscosity, which suggest DNA partial intercalation interaction, and the structure-activity relationship studies suggest that the anticancer activities increase with the increasing lipophilicities of the compounds, roughly consistent with their DNA-binding activities.

Drosophila melanogaster frataxin: protein crystal and predicted solution structure with identification of the iron-binding regions.

Friedreich's ataxia (FRDA) is a hereditary cardiodegenerative and neurodegenerative disease that affects 1 in 50 000 Americans. FRDA arises from either a cellular inability to produce sufficient quantities or the production of a nonfunctional form of the protein frataxin, a key molecule associated with mitochondrial iron-sulfur cluster biosynthesis. Within the mitochondrial iron-sulfur cluster (ISC) assembly pathway, frataxin serves as an allosteric regulator for cysteine desulfurase, the enzyme that provides sulfur for [2Fe-2S] cluster assembly. Frataxin is a known iron-binding protein and is also linked to the delivery of ferrous ions to the scaffold protein, the ISC molecule responsible for the direct assembly of [2Fe-2S] clusters. The goal of this report is to provide structural details of the Drosophila melanogaster frataxin ortholog (Dfh), using both X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, in order to provide the foundational insight needed to understand the structure-function correlation of the protein. Additionally, NMR iron(II) titrations were used to provide metal contacts on the protein to better understand how it binds iron and aids its delivery to the ISC scaffold protein. Here, the structural and functional similarities of Dfh to its orthologs are also outlined. Structural data show that bacterial, yeast, human and Drosophila frataxins are structurally similar, apart from a structured C-terminus in Dfh that is likely to aid in protein stability. The iron-binding location on helix 1 and strand 1 of Dfh is also conserved across orthologs.

Molecular characteristics of proteins within the mitochondrial Fe-S cluster assembly complex.

Iron-Sulfur (Fe-S) clusters are essential for life, as they are widely utilized in nearly every biochemical pathway. When bound to proteins, Fe-S clusters assist in catalysis, signal recognition, and energy transfer events, as well as additional cellular pathways including cellular respiration and DNA repair and replication. In Eukaryotes, Fe-S clusters are produced through coordinated activity by mitochondrial Iron-Sulfur Cluster (ISC) assembly pathway proteins through direct assembly, or through the production of the activated sulfur substrate used by the Cytosolic Iron-Sulfur Cluster Assembly (CIA) pathway. In the mitochondria, Fe-S cluster assembly is accomplished through the coordinated activity of the ISC pathway protein complex composed of a cysteine desulfurase, a scaffold protein, the accessory ISD11 protein, the acyl carrier protein, frataxin, and a ferredoxin; downstream events that accomplish Fe-S cluster transfer and delivery are driven by additional chaperone/delivery proteins that interact with the ISC assembly complex. Deficiency in human production or activity of Fe-S cluster containing proteins is often detrimental to cell and organism viability. Here we summarize what is known about the structure and functional activities of the proteins involved in the early steps of assembling [2Fe-2S] clusters before they are transferred to proteins devoted to their delivery. Our goal is to provide a comprehensive overview of how the ISC assembly apparatus proteins interact to make the Fe-S cluster which can be delivered to proteins downstream to the assembly event.