While medicinal inorganic chemistry has been practised for over 5000 years, it was not until the late 1800s when Alfred Werner published his ground-breaking research on coordination chemistry that we ...began to truly understand the nature of the coordination bond and the structures and stereochemistries of metal complexes. We can now readily manipulate and fine-tune their properties. This had led to a multitude of complexes with wide-ranging biomedical applications. This review will focus on the use and potential of metal complexes as important therapeutic agents for the treatment of cancer. With major advances in technologies and a deeper understanding of the human genome, we are now in a strong position to more fully understand carcinogenesis at a molecular level. We can now also rationally design and develop drug molecules that can either selectively enhance or disrupt key biological processes and, in doing so, optimize their therapeutic potential. This has heralded a new era in drug design in which we are moving from a single- toward a multitargeted approach. This approach lies at the very heart of medicinal inorganic chemistry. In this review, we have endeavored to showcase how a "multitargeted" approach to drug design has led to new families of metallodrugs which may not only reduce systemic toxicities associated with modern day chemotherapeutics but also address resistance issues that are plaguing many chemotherapeutic regimens. We have focused our attention on metallodrugs incorporating platinum and ruthenium ions given that complexes containing these metal ions are already in clinical use or have advanced to clinical trials as anticancer agents. The "multitargeted" complexes described herein not only target DNA but also contain either vectors to enable them to target cancer cells selectively and/or moieties that target enzymes, peptides, and intracellular proteins. Multitargeted complexes which have been designed to target the mitochondria or complexes inspired by natural product activity are also described. A summary of advances in this field over the past decade or so will be provided.
Supply chains (SC) are generally complex and are characterized by numerous activities spread over multiple functions and organizations, which pose interesting challenges for effective SC ...coordination. To meet these challenges, SC members must work towards a unified system and coordinate with each other. A systematic literature review is presented in this paper to throw light on the importance of SC coordination. The objectives of this paper are to: report and review various perspectives on SC coordination issues, understand and appreciate various mechanisms available for coordination and identify the gaps existing in the literature. A framework is suggested indicating scope for further research.
Display omitted
•Coordination of betaine to alkaline earth (new!) and rare earth cations.•Syntheses from solution and via grinding were investigated.•Neutral zwitterionic ligand allows for multiple ...coordination modes.•Hardly predictable stoichiometries were observed.•Structures range from mono- over oligonuclear to coordination polymers.
We report the synthesis and structure of coordination compounds in which betaine acts as a ligand towards Pearson-hard cations. The overall neutral zwitterion was reacted with the corresponding nitrate salts in polar protic solvents such as water or methanol or mechanochemically by grinding the reaction partners. Reaction of MgII, CaII, SrII and BaII resulted in the first alkaline earth derivatives of betaine. The products comprise mono- and oligonuclear cations for the light, and cationic chain polymers for the heavy group2 metals. In the case of CaII, the betaine stoichiometry was decisive for the outcome of the reaction; solids with 1:4 and the less intuitive 3:16 cation to ligand ratio have been structurally characterized. Coordination numbers increase from six for MgII and CaII over seven and eight for the two independent SrII to eight for BaII cations. Coordination of betaine to trivalent Y, La and Pr results in the formation of structurally related dinuclear cations, with coordination numbers eight for Y and nine for the larger lanthanides. Water and betaine compete for coordination; aqua ligands prevail for the smaller, betaine for the larger cations. Betaine coordination to all these hard cations occurs in various modes, similar to those of other carboxylates. Bridging betaine subtends cation⋯cation distances between 4.5 and 6.1 Å. Nitrate coordination was only observed in the BaII chain polymer.
Due to the increasing impact of cancer on worldwide mortality, more and more attention is being devoted to the investigation of novel anticancer strategies. Among these, chemotherapy plays a key role ...in fighting cancer. This explains the increasing engagement of both the pharmaceutical industry and academia towards the discovery of new chemotherapeutic agents. In recent years, metal-based drugs have attracted much attention due to their atypical physico-chemical properties compared to organic molecules. After the approval of cisplatin as a chemotherapeutic agent in 1978, several types of metal-based drugs have been explored. Among them, Ru-based anticancer drug candidates have become a central subject in this research field. However, most of the Ru-based compounds investigated over the last two decades express their cytotoxicity with a mechanism of action involving, among others, a ligand-exchange mechanism. In this Review, we give a complete overview of a specific class of antiproliferative ruthenium complexes, namely coordinatively saturated and substitutionally inert Ru(ii) polypyridyl complexes. This implies that the cytotoxicity observed comes from the entire complex and not from ligand-exchange. In this Review, we present monomeric and dimeric Ru(ii) polypyridyl complexes, which have been found to be toxic to cancer cells. More specifically, monomeric Ru(ii) polypyridyl complexes are analysed considering their direct interaction or not with DNA as the cause of cell death, while dimeric Ru(ii) polypyridyl complexes are classified according to their biological targets. Very importantly, the cellular targets of these complexes are discussed in detail. Indeed, several targets were identified and different mechanisms of action were suggested.
This tutorial review covers the recent advances made in the study of gold complexes containing N-heterocyclic carbene ligands with biological properties. The great stability, ease of modulation of ...the electronic properties and excellent σ-donating capacity displayed by NHCs allow gold-NHC derivatives to reach high stability in biological media and relatively good internalization into cells and for that they have emerged as excellent potential chemotherapeutics. The new gold-NHC derivatives show superior anticancer activity compared to other standards such as Cisplatin or Auranofin. In addition, the application of gold-NHC complexes in the treatment of other human diseases as antibacterial, antioxidant and antiparasitic agents is reviewed for the first time.
PDF
