Current status of platinum-based antitumor drugs.

Light-Emitting Self-Assembled Materials Based on d(8) and d(10) Transition Metal Complexes.

Chromium− and Manganese−salen Promoted Epoxidation of Alkenes

Theoretical studies on reactions of transition-metal complexes.

ion and completion of the cyclometalation reaction are feasible and produce the cyclometalated complex 205. Notably, addition of a strong acid reverts the cyclometalation and regenerates the agostic species 204. Small changes in the rhodium precursor significantly modify the product outcome and lead at fast rates to the cyclometalated complex 203, that is, the final oxidative addition product S. Similarly, alkene C-H bond activation has been observed to occur readily in a PCP ligand setting.348 Milstein and co-workers developed a procedure for preparing the cyclometalated PCP, PCN, or PCO pincer complexes 209 by rhodium-mediated cleavage of a strong Caryl-Calkyl bond (Scheme 87).32,349,350 Kinetically, Calkyl-H bond activation is competitive and complex 208 is formed as a second product at essentially similar rates. However, C-C bond cleavage appears to be the thermodynamically more favored process. Obviously, the higher energy required for Caryl-Calkyl bond activation (bond dissociation energy 427 kJ mol-1) compared to C-H bond breaking (368 kJ mol-1) is compensated by the stronger Rh-Caryl bond and the formation of two fiverather than six-membered metallacycles. Because rhodium-mediated Caryl-Calkyl and Calkyl-H bond activations in 206 are thermodynamically and kinetically very similar processes,351 subtle changes in the ligand parameters strongly affect the reaction outcome. For example, PPh2 donors induce C-H bond cleavage to afford 208d exclusively at ambient temperatures. C-C activation and formation of 209d is only induced upon heating under H2 atmosphere,352 presumably because these conditions allow the product selectivity to be controlled thermodynamically. In contrast, bulky PtBu2 donors as in 206a promote C-C bond activation already at room temperature, and the aryl complex 209a is the only product observed. Similarly, replacing one phosphine donor by a harder NEt2 group or the use of less basic phosphinite donors results in selective C-C bond cleavage at room temperature. These preferences suggest steric factors to play a more dominant role than electronic differences in determining the C-C vs C-H selectivity. Steric congestion induced by the donor substituents has been proposed to arrange the orbitals of the metal center to be directed toward the C-C bond rather than toward the C-H bond.353 Kinetic investigations have identified the coordination compound 207 as a common intermediate of Calkyl-H and the Caryl-Calkyl bond activation. On the basis of the similar rates for both cleavage processes and because of the absence of any detectable intermediate, formation of 207 and not C-H or C-C bond activation appears to be rate-limiting. While displacement of a weakly bound olefin ligand in the metal precursor may be fast, formation of the 8-membered metallacycle in 207 may be less favored, especially due to the potential for forming diand polymeric coordination compounds. It is worth noting that, upon substituting the PCP pincer ligand to a PCN donor array, the coordination complex 207c becomes stable at low temperature and has been spectroscopically characterized.354 As a consequence, the rate-determining step is shifted to a later stage on the reaction coordinate. Notably, slight modifications in the metal precursor, that is, utilization of [Rh(C2H4)(CO)(solv)2]BF4 instead of [RhCl(C2H4)2]2, alters the stability of the intermediates and produces complex 210 (Scheme 88).355 This complex may be represented by an agostic interaction of the C-C bond with the rhodium center, or alternatively by an arenium structure including an sp3-hybridized ipso carbon. Because of only weak Cipso-Rh interactions in solution (e.g., the absence of any 103Rh coupling), the agostic description is favored. The different product outcome has been presumed to originate from the reduced electron density at the cationic rhodium(I) center due to the strongly withdrawing CO ligand and the relatively weak Rh-N bond. This configuration Scheme 87 Scheme 86 Cyclometalation Using d-Block Transition Metals Chemical Reviews, 2010, Vol. 110, No. 2 603

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Cyclometalation Using d-Block Transition Metals: Fundamental Aspects and Recent Trends

The clinical success of cisplatin (cis -diamminedichloroplatinum(II)) in antitumor chemotherapy has encouraged an all-out search for analogues with lower toxicity, improved therapeutic index and increased activity. Literally thousands of analogues, obtained by replacement of the ammine- and chloro-ligands by other amines and anionic ligands, respectively, have been systematically screened for activity in experimental tumor models. Some of these analogues have been selected for clinical evaluation, but only very few of them appear to be promising antitumor agents. More recently, cisplatin analogues have been designed and synthesized on the basis of, inter alia, the following considerations: 1) platinum complexes with carrier molecules as ligands should prove useful for achieving increasing drug concentration in tumor tissues; 2) platinum complexes with chemotherapeutic agents as ligands could afford polyfunctional drugs with synergistic action; 3) complexes containing more than one platinum atom might be more effective than complexes containing only one platinum atom; 4) platinum complexes could be used as sensitizers in radiation therapy. In this paper, we shall give a brief account of the “traditional” analogues, and then critically discuss what we believe could be the new trends in the design of cisplatin analogues.

New Cisplatin Analogues—On the Way to Better Antitumor Agents

This paper presents some copper(II) complexes of salen analogues in which the two salicylaldehyde moieties carry different (electron donor, D, and acceptor, A) substituents in position 5, producing a push−pull charge asymmetry. The X-ray structures of some compounds show the presence of pairs of stacked molecules with head-to-tail intermolecular associations. The geometries of all complexes have been optimized through density functional theory (DFT) studies, which have shown that a major influence on the coordination bond lengths is given by the presence of the electron acceptor NO2 group. Such an influence operates mainly on the Cu−phenolato bonds:  elongation of the Cu−O distance of the 5-nitrosalicylaldehyde moiety, with a concomitant decrease of the other Cu−O distance; the Cu−N bonds are less affected. The D groups have only a minor influence. The nonlinear optical responses, μgβvec, of some molecules have been determined by EFISH measurements, and the βvec values have been obtained using the DFT-cal...

Copper(II) complexes of salen analogues with two differently substituted (push-pull) salicylaldehyde moieties. A study on the modulation of electronic asymmetry and nonlinear optical properties

Kinetic investigation of some electronic and steric factors in oxidative addition reactions to Vaska's compound

Homogeneous catalysis by transition metal complexes I. The homogeneous cyclohexene oxidation catalysed by low valent tertiary phosphine-transition metal complexes

The relevance of cis and trans influences of some anionic ligands X and Y in cis-[PtX(2)(PPh(3))(2)] and cis-[PtXY(PPh(3))(2)] complexes have been studied by the X-ray crystal structures of several derivatives (X(2) = (AcO)(2) (3), (NO(3))(2) (5), Br(2) (7), I(2) (11); and XY = Cl(AcO) (2), Cl(NO(3)) (4), and Cl(NO(2)) (13)), density functional theory (DFT) calculations, and one bond Pt-P coupling constants, (1)J(PtP). The latter have allowed an evaluation of the relative magnitude of both influences. It is concluded that such influences act in a cooperative way and that the cis influence is not irrelevant when rationalizing the (1)J(PtP) values, as well as the experimental Pt-P bond distances. On the contrary, in the optimized geometries, evaluated through B3LYP/def2-SVP calculations, the cis influence was not observed, except for compounds ClPh (21), Ph(2) (22), and, to a lesser extent, Cl(NO(2)) (13) and (NO(2))(2) (14). A natural bond order analysis on the optimized structures, however, has shown how the cis influence can be related to the s-character of the Pt hybrid orbital involved in the Pt-P bonds and the net atomic charge on Pt. We have also found that in the X-ray structures of cis-[PtX(2)(PPh(3))(2)] complexes the two Pt-X and the two Pt-P bond lengths are different each other and are related to the conformation of the phosphine groups, rather than to the crystal packing, since this feature is observed also in the optimized geometries.

Alessandro Pasini

Papers

New Cisplatin Analogues—On the Way to Better Antitumor Agents

Copper(II) complexes of salen analogues with two differently substituted (push-pull) salicylaldehyde moieties. A study on the modulation of electronic asymmetry and nonlinear optical properties

Kinetic investigation of some electronic and steric factors in oxidative addition reactions to Vaska's compound

Homogeneous catalysis by transition metal complexes I. The homogeneous cyclohexene oxidation catalysed by low valent tertiary phosphine-transition metal complexes

Cooperation between Cis and Trans Influences in cis-PtII(PPh3)2 Complexes: Structural, Spectroscopic, and Computational Studies