The platinum drugs, cisplatin, carboplatin, and oxaliplatin, prevail in the treatment of cancer, but new platinum agents have been very slow to enter the clinic. Recently, however, there has been a surge of activity, based on a great deal of mechanistic information, aimed at developing nonclassical platinum complexes that operate via mechanisms of action distinct from those of the approved drugs. The use of nanodelivery devices has also grown, and many different strategies have been explored to incorporate platinum warheads into nanomedicine constructs. In this Review, we discuss these efforts to create the next generation of platinum anticancer drugs. The introduction provides the reader with a brief overview of the use, development, and mechanism of action of the approved platinum drugs to provide the context in which more recent research has flourished. We then describe approaches that explore nonclassical platinum(II) complexes with trans geometry or with a monofunctional coordination mode, polynuclea...

The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

: The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

The nature and characteristics of the CH/π interaction are discussed by comparison with other weak molecular forces such as the CH/O and OH/π interaction. The CH/π interaction is a kind of hydrogen bond operating between a soft acid CH and a soft base π-system (double and triple bonds, C6 and C5 aromatic rings, heteroaromatics, convex surfaces of fullerenes and nanotubes). The consequences of CH/π hydrogen bonds in supramolecular chemistry are reviewed on grounds of recent crystallographic findings and database analyses. The topics include intramolecular interactions, crystal packing (organic and organometallic compounds), host/guest complexes (cavity-type inclusion compounds of cyclodextrins and synthetic macrocyclic hosts such as calixarenes, catenanes, rotaxanes and pseudorotaxanes), lattice-inclusion type clathrates (including liquid crystals, porphyrin derivatives, cyclopentadienyl compounds and C60 fullerenes), enantioselective clathrate formation, catalytic enantioface discriminating reactions and solid-state photoreaction. The implications of the CH/π concept for crystal engineering and drug design are evident.

CH/π hydrogen bonds in crystals

6.1.2. Aqueous V(III) Chemistry 877 6.1.3. Oxidation State of Vanadium in Tunicates 878 6.1.4. Uptake of Vanadate into Tunicates 879 6.1.5. Vanadium Binding Proteins: Vanabins 879 6.1.6. Model Complexes and Their Chemistry 880 6.1.7. Catechol-Based Model Chemistry 880 6.1.8. Vanadium Sulfate Complexes 881 6.2. Fan Worm Pseudopotamilla occelata 883 7. Vanadium Nitrogenase 883 7.1. Nitrogenases 883 7.2. Biochemistry of Nitrogenase 884 7.3. Clusters in Nitrogenase and Model Systems: Structure and Reactivity 885

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The chemistry and biochemistry of vanadium and the biological activities exerted by vanadium compounds.

Triggered by the resounding success of cisplatin, the past decades have seen tremendous efforts to produce clinically beneficial analogues. The recent achievement of oxaliplatin for the treatment of colon cancer should, however, not belie the imbalance between a plethora of investigated complexes and a very small number of clinically approved platinum drugs. Strategies opening up new avenues are increasingly being sought using complexes of metals other than platinum such as ruthenium or gallium. Based on the chemical differences between these metals, the spectrum of molecular mechanisms of action and potential indications can be broadened substantially. Other approaches focus on complexes with tumour-targeting properties, thereby maximizing the impact on cancer cells and minimizing the problem of adverse side effects, and complexes with biologically active ligands.

Antitumour metal compounds: more than theme and variations.

Heavy metals in drinking waters from Mount Amiata (Tuscany, Italy). Possible risks from arsenic for public health in the Province of Siena

Metal complexes of the antiinflammatory drug piroxicam

Mechanistic and Stereochemical Investigation of Imino Ethers Formed by Alcoholysis of Coordinated Nitriles: X-ray Crystal Structures of cis- and trans-Bis(1-imino-1-methoxyethane)dichloroplatinum(II)

Mono- and bisnitrile platinum complexes, [PtCl 3 (NCR)] - and cis- and trans-[PtCl 2 (NCR) 2 ] (R=Bu', Me and Ph), hydrolyze to amidate amide and mixed amide-nitrile complexes. The amide ligands generally adopt the enol tautomeric form and coordinate to platinum through nitrogen. The presence of two amides cis to one another plays a critical role in favoring the association of platinum units in dimers. For example, molecules of cis-[PtCl 2 (HN=C-(OH)Bu t } 2 ] 2 , 7b, comprise two monomeric units, placed face to face, with a Pt-Pt distance of 3.165(1) A and four interplanar N-H...Cl hydrogen bonds

Platinum amides from platinum nitriles: x-ray crystal structures of the unbridged dinuclear compounds bis[bis(1-imino-1-hydroxy-2,2-dimethylpropane)dichloroplatinum(II)] and bis[bis(1-imino-1-hydroxy-2,2-dimethylpropane)(1-amino-1-oxo-2,2-dimethylpropane)dichloroplatinum(II)]

Unusual coordinating behavior by three non-steroidal anti-inflammatory drugs from the oxicam family towards copper(II). Synthesis, X-ray structure for copper(II)–isoxicam, –meloxicam and –cinnoxicam-derivative complexes, and cytotoxic activity for a copper(II)–piroxicam complex

Renzo Cini

Papers

Heavy metals in drinking waters from Mount Amiata (Tuscany, Italy). Possible risks from arsenic for public health in the Province of Siena

Metal complexes of the antiinflammatory drug piroxicam

Mechanistic and Stereochemical Investigation of Imino Ethers Formed by Alcoholysis of Coordinated Nitriles: X-ray Crystal Structures of cis- and trans-Bis(1-imino-1-methoxyethane)dichloroplatinum(II)

Platinum amides from platinum nitriles: x-ray crystal structures of the unbridged dinuclear compounds bis[bis(1-imino-1-hydroxy-2,2-dimethylpropane)dichloroplatinum(II)] and bis[bis(1-imino-1-hydroxy-2,2-dimethylpropane)(1-amino-1-oxo-2,2-dimethylpropane)dichloroplatinum(II)]

Unusual coordinating behavior by three non-steroidal anti-inflammatory drugs from the oxicam family towards copper(II). Synthesis, X-ray structure for copper(II)–isoxicam, –meloxicam and –cinnoxicam-derivative complexes, and cytotoxic activity for a copper(II)–piroxicam complex