A critically important process in catalysis is the formation of an active catalyst from the combination of a metal precursor and a ligand, as the efficacy of this reaction governs the amount of active catalyst. This Review is a comprehensive overview of reactions catalyzed by nickel and an added bidentate phosphine, focusing on the steps transforming the combination of precatalyst and ligand into an active catalyst and the potential effects of this transformation on nickel catalysis. Reactions covered include common cross-coupling reactions, such as Suzuki, Heck, Kumada, and Negishi couplings, addition reactions, cycloadditions, C-H functionalizations, polymerizations, hydrogenations, and reductive couplings, among others. Overall, the most widely used nickel precatalyst with free bidentate phosphines is Ni(cod)2, which accounts for ∼50% of the reports surveyed, distantly followed by Ni(acac)2 and Ni(OAc)2, which account for ∼10% each. By compiling the reports of these reactions, we have calculated statistics of the usage and efficacy of each ligand with Ni(cod)2 and other nickel sources. The most common bidentate phosphines are simple, relatively inexpensive ligands, such as DPPE, DCPE, DPPP, and DPPB, along with others with more complex backbones, such as DPPF and Xantphos. The use of expensive chiral phosphines is more scattered, but the most common ligands include BINAP, Me-Duphos, Josiphos, and related analogs.

Trends in the Usage of Bidentate Phosphines as Ligands in Nickel Catalysis.

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

V-shaped bis-coumarin based fluorescent probe for detecting palladium in natural waters.

A series of new dinuclear platinum(ii) complexes with the general formula [Pt2(μ-HL)4] (1-4), where H2L is 4-[(5-chloro-2-hydroxy-benzylidene)-amino]-3-R-1,2,4-triazole-5-thione: R = H (1), methyl (2), ethyl (3) and propyl (4), were synthesized and characterized. The X-ray crystal structures of 2, 3 and 4 reveal that the two platinum atoms form a paddlewheel core with four chelating triazole ligands as bridges, revealing a radically different structure than those of the traditional anticancer platinum(ii) complexes. These complexes show higher in vitro antiproliferative activity against human liver hepatocellular carcinoma (HepG2) and human breast adenocarcinoma (MCF7) than human lung cancer (A549) and human normal hepatocyte (HL-7702) cell lines. In particular, 3 exhibits antiproliferative activity (IC50 = 5.5 μM) against HepG2 cells comparable to that of cisplatin. Different from the traditional anticancer platinum(ii) complexes with high DNA affinity, 3 binds very weakly to DNA. Upon comparison, it exhibits potent inhibiting activity against protein tyrosine phosphatases 1B (PTP1B, IC50 = 16 μM) through possible binding to its active sites and its binding constant is 5.28 × 104 M-1. The results suggest that the antiproliferative mechanism of 3 against HepG2 cells may be different from that of cisplatin.

Syntheses, crystal structures, and biological evaluations of new dinuclear platinum(II) complexes with 1,2,4-triazole derivatives as bridging ligands

For the development of anticancer drugs with higher activity and reduced toxicity, two approaches were combined: preparation of platinum(IV) complexes exhibiting higher stability compared to their platinum(II) counterparts and loading them into mesoporous silica SBA-15 with the aim to utilise the passive enhanced permeability and retention (EPR) effect of nanoparticles for accumulation in tumour tissues. Three conjugates based on a cisplatin scaffold bearing the anti-inflammatory drugs naproxen, ibuprofen or flurbiprofen in the axial positions (1, 2 and 3, respectively) were synthesised and loaded into SBA-15 to afford the mesoporous silica nanoparticles (MSNs) SBA-15|1, SBA-15|2 and SBA-15|3. Superior antiproliferative activity of both free and immobilised conjugates in a panel of four breast cancer cell lines (MDA-MB-468, HCC1937, MCF-7 and BT-474) with markedly increased cytotoxicity with respect to cisplatin was demonstrated. All compounds exhibit highest activity against the triple-negative cell line MDA-MB-468, with conjugate 1 being the most potent. However, against MCF-7 and BT-474 cell lines, the most notable improvement was found, with IC50 values up to 240-fold lower than cisplatin. Flow cytometry assays clearly show that all compounds induce apoptotic cell death elevating the levels of both early and late apoptotic cells. Furthermore, autophagy as well as formation of reactive oxygen species (ROS) and nitric oxide (NO) were elevated to a similar or greater extent than with cisplatin. 

Cisplatin−cyclooxygenase inhibitor conjugates, free and immobilised in mesoporous silica SBA-15, prove highly potent against triple-negative MDA-MB-468 breast cancer cell line

This review presents the main advances in the design of antitumor platinum complexes over the last five years. Particular attention is paid to unconventional antitumor platinum compounds (complexes in the trans configuration, Pt(IV) complexes with S and P donor ligands, multinuclear complexes).

Ya. M. Stanishevskii

Papers

Design and Antitumor Activity of Platinum Complexes