Chemistry and applications of metal complexes

Welcome to this themed issue of Dalton Transactions, associated with the 2012 Edition of the International Symposium on Metal Complexes (ISMEC2012) held in Lisbon, from 18th to 22nd June 2012, and organized by the European Group of Thermodynamics of Metal Complexes. In this issue we seek to show the most important international breakthrough developments on metal complexes, focusing on their properties and wide range of applications to tackle the challenges in human health/disease and the environment.

Several topics have been presented and discussed under the scope of this Symposium, especially focused on the chemistry and applications of metal complexes, notably: solution equilibria and coordination chemistry, metal complexes of biological and environmental interest, supramolecular chemistry, metal–complex interactions with biomolecules, nanostructured metal complexes, metals in diseases (transport, homeostasis and toxicity), metal-based drugs (therapy and diagnosis), metalloenzymes (metal binding and models), analytical methods and sensors based on metal complexes, computational modeling.

The conference attracted over 200 participants from 27 countries and it included 5 Plenary Lectures, 10 Keynote Lectures, 51 Oral Communications and 114 posters. The range of cutting-edge chemistry presented by the Plenary speakers was wider than ever, as evidenced by the titles of the corresponding fascinating talks: Prof. Robert R. Crichton (University Catholique de Louvain, Belgium), “Redox metals in neurodegenerative diseases, and therapeutic perspectives”; Prof. Kenneth N. Raymond (University of California, Berkeley, EUA), “Metal ion selective sequestering agents, with selective properties”; Prof. Chris Orvig (University of British Columbia, Vancouver, Canada), “Medicinal inorganic chemistry”; Prof. Carlos F. G. C. Geraldes (Universidade de Coimbra, Portugal), “Metal-based chelates and nanosystems for multimodal molecular imaging applications”; Prof. Luca Prodi (University of Bologna, Italy), “Luminescent silica nanoparticles: extending the frontiers of brightness”.

However, it should be emphasized that all the participants contributed to five exciting days of this high-quality scientific forum with a great deal of lively and stimulating discussion. So this themed issue appears as a timely collective volume which brings together manuscripts from key contributors to the various topical fields presented at this Conference. The papers contained in this issue were all peer-reviewed and accepted for publication in Dalton Transactions. Although the theme is somehow vast, we hope that this selection of papers may be used as a learning guide for those new in the area or as a refresher for those already working in the area. Twenty-six invited manuscripts are included in the themed issue and they are briefly introduced below.

A great deal of work is devoted to the solution equilibrium and coordination chemistry of several systems involving divalent transition metal ions M(II) and a variety of compounds, ranging from peptide- to macrocycle-based ligands, all of them with great biological interest. As representative examples of the complexation with peptidic fragments, the following studies can be referred: the interaction of a peptide fragment of the Helicobacter's pylori with Ni(II) and Zn(II), in order to understand the coordination mode and competition between these metal ions (DOI: 10.1039/C2DT32195E); the interaction of divalent cations (M = Zn, Cu, Mg) with peptide fragments from Parkinson's disease genes (DOI: 10.1039/C2DT32222F); the formation of Cu and Zn complexes with triethylenetetramine and its human acetyl metabolites accumulated in the body and associated with the treatment of Wilson's disease (DOI: 10.1039/C2DT32252H); the complexation of Cu(II) with decapeptides containing three His residues (DOI: 10.1039/C3DT32384F), as models of metalloenzymes. As representative examples of the study of complexes with functionalized macrocylic ligands, this issue includes several papers involving solution studies and X-ray crystal structures: the complexation of Cu(II) with a cyclam tetrapropionic acid, also presenting biodistribution studies (DOI: 10.1039/C2DT32356G); complexation of cyclen derivatives containing two trans-methylnitrophenolic pendant arms with Cu(II) and Zn(II) (DOI: 10.1039/C2DT32363J); macrocyclic supramolecular systems, as models of some proteins, involving equilibrium and kinetic studies on complex formation/decomposition and movement of Cu²⁺ metal ions within polytopic receptors (DOI: 10.1039/C3DT32220C). A structural approach is also presented based on the X-ray crystal structures of several Cu(II) complexes, involving a discussion on molecular recognition and conformational aspects of Cu(II) complexes with mixed nucleobase ligands, namely deaza-adenine ligands (DOI: 10.1039/C2DT32191B).

The development and study of iron(III) chelators deserved also special attention because, when in excess or misplaced, this biometal is implicated in several diseases. A tripodal hydroxypyrimidinone-based ligand was evaluated in solution and in vivo as sequestering agent for Fe(III) and other trivalent hard metal ions, for metal overload disorders, such as β-thalassemia (DOI: 10.1039/C2DT32361C). Concerning the problem of misplaced iron in neurodegenerative disorders, namely Alzheimer's disease, a paper deals with polyfunctional hydroxypyridinone chelators which, besides the iron-chelation, present other neuroprotective properties, namely anti-oxidation and anti-amyloid β aggregation (DOI: 10.1039/C3DT50406A). Two interesting articles deal with fluorescent sensors for metal ions and metal complexes, involving solution and in vitro studies: one article focus the influence of the binding properties on the optical response of a fluorescent chemosensor, namely a spirocyclic derivative of rhodamine B for probing the presence of Fe(III) (DOI: 10.1039/C2DT32198J); the other one presents bifunctional boron–dipyrromethene fluorescent dies (BODIPY) coupled to phosphane complexes with Au, Ru and Os, that have been studied as potential metal-based therapeutic and diagnostic (theranostic) agents (DOI: 10.1039/C2DT32055J).

Dealing with novel “smart” materials, two papers employ functionalized room temperature ionic liquids (IL) which can establish strong interactions with different metal ions, including lanthanides. The novel materials have been studied and discussed under the perspective of their application as metal complexes, namely as new luminescent IL materials (DOI: 10.1039/C2DT32218H); also as new ligands (new IL metal-extractor materials) with the proposal on a new mechanistic model for the liquid–liquid extraction (DOI: 10.1039/C3DT32159B). Still related with sorption of metals from the environment, it is worth to refer a paper involving the study of supramolecular receptors in solid phase as sensors for selective extraction of radionuclides, namely ⁹⁹Tc and ¹⁸⁸Re in the form of TcO₄⁻ and ReO₄⁻, respectively (DOI: 10.1039/C2DT32211K). Another paper appears as an interesting contribution of the chemistry to our cultural heritage, namely dealing with a multi-analytical approach to study the interaction of inorganic pigments with proteinaceous binders, aimed at understanding the ageing process of paintings and frescos (DOI: 10.1039/C2DT32203J).

Another common subtheme in this issue is the study of metallodrugs, which are usually complexes of non-essential metal ions with specific ligands aimed at diagnostic or therapeutic roles. Some papers are more concerned with the study of the properties of the metal complexes while others are mainly focused on the interaction of the metal complexes with biomolecules.

The study of lanthanide complexes as metallodrugs appears herein in the perspective of diagnostic or therapeutic application. Thus, one paper deals with new Tris-3,4-HOPO lanthanide complexes, in particular the Gd(III) complex as a potential MR imaging probe, a study focused on the complex stability and the magnetic properties (DOI: 10.1039/C2DT32237D); another paper deals with lanthanide complexes with a set of mono-3,4-HOPO ligands, including the study of complex stability and also the binding interaction with hydroxyapatite, for potential use in the treatment of osteoporosis (DOI: 10.1039/C2DT32373G). Still under the theme of metallodrugs, several papers reported the study of ruthenium complexes with different oxidation states, aimed at applications in medicine and industry. In particular, “half-sandwich” Ru(II)(arene) hydroxy-flavone coordinated complexes were evaluated in terms of stability and interaction with DNA, showing anti-topoisomerase and anticancer activity (DOI: 10.1039/C2DT32206D); structural approaches based on X-ray of the metal complexes were conducted to the study of Ru(III) complexes with triazolopyrimidine ligands, showing anti-tumor activity (DOI: 10.1039/C2DT32216A); also ruthenium complexes with different oxidation states (III/IV), coordinated with bidentate N,O- or N,N-donor ligands, have been fully characterized in the solid state including the magnetic properties (DOI: 10.1039/C3DT32214A); the interaction between CO releasing Ru(II) complex prodrugs with a lysozyme (protein model) was assessed by different techniques, including an X-ray crystallography study of the corresponding adducts (DOI: 10.1039/C2DT32174B); another interesting communication deals with the in situ formation of multidentate N-donor ligands (urotropine and scorpionate-tripode) and corresponding Cd(II) complexes, which are fully characterized by X-ray crystallography and spectroscopy (DOI: 10.1039/C3DT32987A).

The importance of computational molecular simulations (from ab initio quantum-chemical to DFT-based methods) is recognized by several authors in this issue. However, three papers made a major focus on these tools for the prediction or the rationalization of metal–complex properties. Two authors report the use of DFT calculations to rationalize the thermodynamic stability of complexes of macrocyclic ligands with different metal ions, in view of their application in metal removal from contaminated environment, namely with a cucurbituril macrocyclic cavity for the ¹³⁷Cesium actinide (DOI: 10.1039/C2DT32180G), and also sulfur-containing macrocycles for sequestration of toxic soft heavy metal ions (e.g., Cd(II) and Hg(II)) (DOI: 10.1039/C3DT32332C). A special reference is also due to the study of inframolecular acid–base and coordination properties of Na(I/Mg(II)-inositol-1,3,4,5,6-pentakisphosphate complexes, which complex stability studies were coupled with several molecular modeling tools (DOI: 10.1039/C2DT31807E).

I am very grateful to Dr Jamie Humphrey, who allowed the association of this special issue of the prestigious journal Dalton Transactions to ISMEC2012. I also thank the Dalton Transactions Editorial team for their professionalism in handling all these manuscripts. I take this opportunity to thank all the colleagues who contributed to this issue and, again, special thanks are due to the ISMEC2012 organizing committee. I hope that you, the readers, enjoy reading the articles in this issue and find them interesting and inspiring.

ISMEC2013 will be held in Burgos, Spain, June 6th to 20th, 2013.

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