Innovative inorganic synthesis

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Ruthenium-Based Heterocyclic Carbene-Coordinated Olefin Metathesis Catalysts

The fascinating story of olefin (or alkene) metathesis (eq 1) began almost five decades ago, when Anderson and Merckling reported the first carbon-carbon double-bond rearrangement reaction in the titanium-catalyzed polymerization of norbornene. Nine years later, Banks and Bailey reported “a new disproportionation reaction . . . in which olefins are converted to homologues of shorter and longer carbon chains...”. In 1967, Calderon and co-workers named this metal-catalyzed redistribution of carbon-carbon double bonds olefin metathesis, from the Greek word “μετάθεση”, which means change of position. These contributions have since served as the foundation for an amazing research field, and olefin metathesis currently represents a powerful transformation in chemical synthesis, attracting a vast amount of interest both in industry and academia

Controlling platinum, ruthenium, and osmium reactivity for anticancer drug design

The main task of the medicinal chemist is to design molecules that interact specifically with derailed or degenerating processes in a diseased organism, translating the available knowledge of pathobiochemical and physiological data into chemically useful information and structures. Current knowledge of the biological and chemical processes underlying diseases is vast and rapidly expanding. In particular the unraveling of the genome in combination with, for instance, the rapid development of structural biology has led to an explosion in available information and identification of new targets for chemotherapy. The task of translating this wealth of data into active and selective new drugs is an enormous, but realistic, challenge. It requires knowledge from many different fields, including molecular biology, chemistry, pharmacology, physiology, and medicine and as such requires a truly interdisciplinary approach. Ultimately, the goal is to design molecules that satisfy all the requirements for a candidate drug to function therapeutically. Therapeutic activity can then be achieved by an understanding of and control over structure and reactivity of the candidate drug through molecular manipulation

Improved catalytic activity of ruthenium–arene complexes in the reduction of NAD+

A series of neutral Ru-II half-sandwich complexes of the type [(eta(6)-arene)Ru(N,N')Cl] where the arene is para-cymene (p-cym), hexamethylbenzene (hmb), biphenyl (bip), or benzene (bn) and N,N' is N-(2-aminoethyl) -4-(trifluoromethyl)benzenesulfonamide (TfEn), N-(2-aminoethyl)-4-toluenesulfonamide (TsEn), or N-(2-aminoethyl)-methylenesulfonamide (MsEn) were synthesized and characterized. X-ray crystal structures of [(p-cym)Ru(MsEn)Cl] (1), [(hmb)Ru(TsEn)Cl] (5), [(hmb)Ru(TfEn)Cl] (6), [(bip)Ru(MsEn)Cl] (7), and [(bip)Ru(TsEn)Cl] (8) have been determined. The complexes can regioselectively catalyze the transfer hydrogenation of NAD(+) to give 1,4-NADH in the presence of formate. The turnover frequencies (TOF) when the arene is varied decrease in the order bn > bip > p-cym > hmb for complexes with the same N,N' chelating ligand. The TOF decreased with variation in the N,N' chelating ligand in the order TfEn > TsEn > MsEn for a given arene. [(bn)Ru(TfEn)Cl] (12) was the most active, with a TOP of 10.4 h(-1). The effects of NAD(+) and formate concentration on the reaction rates were determined for [(p-cym)Ru(TsEn)Cl] (2). Isotope studies implicated the formation of [(arene)Ru(N,N')(H)] as the rate-limiting step. The coordination of formate and subsequent CO2 elimination to generate the hydride were modeled computationally by density functional theory (DFT). CO2 elimination occurs via a two-step process with the coordinated formate first twisting to present its hydrogen toward the metal center. The computed barriers for CO2 release for arene = benzene follow the order MsEn > TsEn > TfEn, and for the Ms En system the barrier followed bn < hmb, both consistent with the observed rates. The effect of methanol on transfer hydrogenation rates in aqueous solution was investigated. A study of pH dependence of the reaction in D2O gave the optimum pH* as 7.2 with a TOF of 1.58 h(-1) for 2. The series of compounds reported here show an improvement in the catalytic activity by an order of magnitude compared to the ethylenediamine analogues

Design of photoactivatable metallodrugs : selective and rapid light-induced ligand dissociation from half-sandwich [Ru([9]aneS3)(N–N′)(py)]2+ complexes

The synthesis of the inert Ru(II) half-sandwich coordination compounds, [Ru([9]aneS3)(bpy)(py)][PF6]2 (1, [9]aneS3 = 1,4,7-trithiacyclononane, bpy = 2,2′-bipyridine, py = pyridine), [Ru([9]aneS3)(en)(py)][PF6]2 (2, en = 1,2-diaminoethane), and [Ru([9]aneN3)(en)(dmso-S)][PF6]2 (3, [9]aneN3 = 1,4,7-triazacyclononane), is reported along with the X-ray crystal structure of 1. We investigated whether these complexes have photochemical properties which might make them suitable for use as pro-drugs in photochemotherapy. Complexes 1 and 2 underwent rapid (minutes) aquation with dissociation of the pyridine ligand in aqueous solution when irradiated with blue light (λ = 420 or 467 nm). The photodecomposition of 3 was much slower. All complexes readily formed adducts with 9-ethylguanine (9-EtG) when this model nucleobase was present in the photolysis solution. Similarly, complex 1 formed adducts with the tripeptide glutathione (GSH), but only when photoactivated. HPLC and MS studies of 1 showed that irradiation promoted rapid formation of 1:1 (major) and 1:2 (minor) adducts of the oligonucleotide d(ATACATGCTACATA) with the fragment {Ru([9]aneS3)(bpy)}2+. Density functional theory (DFT) calculations and time-dependent DFT reproduced the major features of the absorption spectra and suggested that the lowest-lying triplet state with 3MLCT character, which is readily accessible via intersystem crossing, might be responsible for the observed dissociative behavior of the excited states. These complexes are promising for further study as potential photochemotherapeutic agents

Unconventional Anticancer Metallodrugs and Strategies to Improve Their Pharmacological Profile

For the past 40 years, metal-based drugs have been widely used for the treatment of cancer. Cisplatin and follow-up drugs carboplatin (ParaplatinTM) and oxaliplatin (EloxatinTM) have been the gold standard for metallodrugs in clinical settings as antineoplastic agents. While effective, these drugs (either alone or in combination therapy) have faced a number of clinical challenges resulting from their limited spectrum of activity, high toxicity leading to significant side effects, resistance, poor water solubility, low bioavailability and short circulating time. In the past 10 years, various unconventional non-platinum metal-based agents have emerged as a potential alternative for cancer treatment. These compounds are highly effective and selective in cancers resistant to cisplatin and other chemotherapeutic agents. Research in this area has recently exploded with a relevant number of patents and clinical trials, in addition to reports in scientific journals. Furthermore, in parallel to the synthesis of coordination and organometallic compounds comprising many different metals and unconventional platinum-based derivatives, researchers are focused on optimizing mechanistic and pharmacological features of promising drug candidates. This Special Issue aims to highlight the latest advances in anticancer metallodrugs with a focus on unconventional anticancer agents, as well as novel activation, targeting and delivery strategies aimed at improving their pharmacological profile

Policing in America: How Racism and Media Framing Impacts the Death rate of Black Men by Police.

Since the turn of the century, a large mass of both African American men and White American men in the United States have been gunned down in numerous proportions when police were involved (Fatal Encounters, 2020). More recently, the deaths of Michael Brown, Philando Castille, Alton Sterling and George Floyd left many in the African American community noticeably bleak and perplexed as a ration of young individual lives were seemingly taken unjustifiably. In the aggregate, many believed this was intentional and thus, immediate action against Law Enforcement was inevitable. Without context, the deaths were just seen as a stain in which black men had to carry the caution of treading lightly just to survive. Over time, there have been many organizations such as Black Lives Matter, who after the death of Trayvon Martin became more vocal in raising a consciousness among non-black citizens that deaths by police must be taken seriously and with accountability at all cost, and even having members within the organization stepping into the arena of political access like Cori Bush and winning a seat in the House of representatives. However, though the underlining deaths of African American males by police runs deep through its complex history of racial injustice, many White males who have had interactions with police may also have met a fate to where their community may have seen their demise as unlawful as well thus reeling in a question as to see if all deaths by police go beyond color or just a fact of law and order. In this literature, I will pose the questions to better understand the research: 1) Is the social structure of the 21st century ways of policing play a part in the deaths of black and white men ; 2) Does media framing incorporate the behavior of the police; and 3) Does the accountability factor of police happen because of public influences? The purpose of the questions is to reveal if there is really a definitive difference in the killings and if there are true biases in relation to those killings

Synthesis Methods, Characterization Techniques and Properties of Some Diruthenium Complexes

This review provides an overview of some diruthenium complexes with respect to their synthesis methods, physical, and chemical properties. Diruthenium complexes discussed in this thesis play a part an important role in various fields, including medicine, catalysis, biology, nanoscience, redox and photoactive materials. Some synthesis methods will be discussed, which help researchers to enhance experimental conditions. Diruthenium complexes are able to bind to DNA and inhibit its replication and protein synthesis, an important property in cancer treatment. A review of synthesis methods and properties of some diruthenium complexes, [Ru2(ibp)4Cl], [Ru2(asp)4Cl], [Ru2(npx)4(H2O)2]PF6, and [Ru2(ind)4(H2O)2]PF6, that exhibited biological activities is presented in this thesis

ANTIPROLIFERATIVE EFFECT AND SELECTIVITY OF SODIUM DICHLORO-BIS [N-PHENYL-5-CHLORO-SALICYLIDENEIMINATO-N, O] RUTHENATE (III) IN VITRO

Ruthenium complexes attracted special attention in recent decades due to their anticancer properties. Since a number of Ru(III) complexes with Schiff bases showed moderate activity to bind DNA, antiproliferative effect of a chloro-ruthenium(III) complex which contains two O,N-bidentate Schiff bases derived from 5-chloro-salicylaldehyde was tested against cervical carcinoma, pancreatic carcinoma, hepatocellular carcinoma, metastatic lesions of colorectal adenocarcinoma and nontumoral cells WI38. The complex showed moderate antiproliferative properties in vitro and significant selectivity to SW620 metastatic lesions of colon cancer. Based on the positive research on ruthenium-based anticancer drugs and their generally moderate cytotoxicity in vitro (IC50) compared to platinum drugs which are in use, the titled compound might be a candidate for investigation in vivo, particularly to SW620.Â

Catalytic Dehydrogenative Coupling of Hydrosilanes with Alcohols for the Production of Hydrogen On-demand: Application of a Silane/Alcohol Pair as a Liquid Organic Hydrogen Carrier

The compound [Ru(p-cym)(Cl)2(NHC)] is an effective catalyst for the room-temperature coupling of silanes and alcohols with the concomitant formation of molecular hydrogen. High catalyst activity is observed for a variety of substrates affording quantitative yields in minutes at room temperature and with a catalyst loading as low as 0.1 mol %. The coupling reaction is thermodynamically and, in the presence of a Ru complex, kinetically favourable and allows rapid molecular hydrogen generation on-demand at room temperature, under air, and without any additive. The pair silane/alcohol is a potential liquid organic hydrogen carrier (LOHC) for energy storage over long periods in a safe and secure way. Silanes and alcohols are non-toxic compounds and do not require special handling precautions such as high pressure or an inert atmosphere. These properties enhance the practical applications of the pair silane/alcohol as a good LOHC in the automotive industry. The variety and availability of silanes and alcohols permits a pair combination that fulfils the requirements for developing an efficient LOHC