Helge Müller-Bunz

Water Oxidation Catalyzed by Strong Carbene-Type Donor-Ligand Complexes of Iridium†

Title Water oxidation catalyzed by strong carbene-type donor ligand complexes of iridium Authors(s) Lalrempuia, Ralte; McDaniel, Neal Donald; Müller-Bunz, Helge; Bernhard, Stefan; Albrecht, Martin Publication date 2010-12 Publication information Angewandte Chemie International Edition, 49 (50): 9765-9768 Publisher Wiley Item record/more information http://hdl.handle.net/10197/3627 Publishers statement This is the authors version of the following article: Lalrempuia, R., McDaniel, N. D., Müller-Bunz, H., Bernhard, S. and Albrecht, M. (2010), Water Oxidation Catalyzed by Strong Carbene-Type Donor-Ligand Complexes of Iridium. Angew. Chem. Int. Ed., 49: þÿ 9 7 6 5 9 7 6 8 w h i c h h a s b e e n p u b l i s h e d i n f i n a l f o r m a t http://dx.doi.org/10.1002/anie.201005260 Publishers version (DOI) 10.1002/anie.201005260

PEPPSI‐Type Palladium Complexes Containing Basic 1,2,3‐Triazolylidene Ligands and Their Role in Suzuki–Miyaura Catalysis

A series of PEPPSI-type palladium(II) complexes was synthesized that contain 3-chloropyridine as an easily removable ligand and a triazolylidene as a strongly donating mesoionic spectator ligand. Catalytic tests in Suzuki-Miyaura cross-coupling reactions revealed the activity of these complexes towards aryl bromides and aryl chlorides at moderate temperatures (50 °C). However, the impact of steric shielding was the inverse of that observed with related normal Nheterocyclic carbenes (imidazol-2-ylidenes) and sterically congested mesityl substituents induced lower activity than small alkyl groups. Mechanistic investigations, including mercury poisoning experiments, TEM analyses, and ESI mass spectrometry, provide evidence for ligand dissociation and the formation of nanoparticles as a catalyst resting state. These heterogeneous particles provide a reservoir for soluble palladium atoms or clusters as operationally homogeneous catalysts for the arylation of aryl halides. Clearly, the substitution of a normal N-heterocyclic carbene for a more basic triazolylidene ligand in the precatalyst has a profound impact on the mode of action of the catalytic system.

Synthesis and structure-activity relationships of the first ferrocenyl-aryl-hydantoin derivatives of the nonsteroidal antiandrogen nilutamide.

We present here the first synthesis of organometallic complexes derived from the nonsteroidal antiandrogen nilutamide, bearing a ferrocenyl substituent at position N(1) or at C(5) of the hydantoin ring; for comparison, we also describe the C(5) p-anisyl organic analogue. All of these complexes retain a modest affinity for the androgen receptor. The N-substituted complexes show a weak or moderate antiproliferative effect (IC 50 around 68 microM) on hormone-dependent and -independent prostate cancer cells, while the C(5)-substituted compounds exhibit toxicity levels 10 times higher (IC 50 around 5.4 microM). This strong antiproliferative effect is probably due to a structural effect linked to the aromatic character of the ferrocene rather than to its organometallic feature. In addition, it seems connected to a cytotoxic effect rather than an antihormonal one. These results open the way toward a new family of molecules that are active against both hormone-dependent and hormone-independent prostate cancer cells.

A symmetry-breaking spin-state transition in iron(III)

Stepping up: A two-step magnetic spin transition with accompanying structural phase transitions is reported for the first time for Fe III. The transitions are observed at 187 K and 90 K on cooling with a hysteretic transition recorded upon heating during the first crossover at 106 K. The intermediate phase persists over 97 K and contains an unprecedented [HS-HS-LS] motif with tripling of the unit cell. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Axially chiral P-N ligands for the copper catalyzed beta-borylation of alpha,beta-unsaturated esters.

The synthesis and resolution of a new axially chiral Quinazolinap ligand are reported. The application of this and other related P-N ligands to the copper catalyzed beta-borylation of alpha,beta-unsaturated esters resulted in conversions of up to 100% and ee values of up to 79%. A diastereomerically pure palladacycle of the new ligand was characterised by X-ray crystallography.

Synthesis, photo-, and electrochemistry of ruthenium bis(bipyridine) complexes comprising a N-heterocyclic carbene ligand.

Analogues of [Ru(bpy)3](2+) were prepared in which one pyridine ligand site is substituted by a N-heterocyclic carbene (NHC) ligand, that is, either by an imidazolylidene with a variable wingtip group R (R = Me, 3a; R = Et, 3b; R = iPr, 3c), or by a benzimidazolylidene (Me wingtip group, 3d), or by a 1,2,3-triazolylidene (Me wingtip group, 3e). All complexes were characterized spectroscopically, photophysically, and electrochemically. An increase of the size of the wingtip groups from Me to Et or iPr groups distorts the octahedral geometry (NMR spectroscopy) and curtails the reversibility of the ruthenium oxidation. NHC ligands with methyl wingtip groups display reversible ruthenium oxidation at a potential that reflects the donor properties of the NHC ligand (triazolylidene > imidazolylidene > benzimidazolylidene). The most attractive properties were measured for the triazolylidene ruthenium complex 3e, featuring the smallest gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) in the series (2.41 eV), a slightly red-shifted absorption profile, and reasonable excited-state lifetime (188 ns) when compared to [Ru(bpy)3](2+). These features demonstrate the potential utility of triazolylidene ruthenium complexes as photosensitizers for solar energy conversion.

Gold(I)-NHC complexes of antitumoral diarylimidazoles: structures, cellular uptake routes and anticancer activities.

Five new heterocyclic gold carbene complexes were prepared, four chlorido-[1,3-dimethyl-4,5-diarylimidazol-2-ylidene]gold complexes 6a-d and a chlorido-[1,3-dibenzylimidazol-2-ylidene]gold complex 11, and three of them were characterised by X-ray single crystal analyses. They were tested for cytotoxicity against a panel of four human cancer cell lines and non-malignant fibroblasts, for tubulin interaction, and for the pathways of their uptake into 518A2 melanoma cells. All complexes showed cytotoxic activity in the micromolar IC(50) range with distinct selectivities for certain cell lines. In stark contrast to related metal-free 1-methyl-4,5-diarylimidazoles, the complexes 6 and 11 did not noticeably inhibit the polymerisation of tubulin to give microtubules. The cellular uptake of complexes 6 occurred mainly via the copper transporter (Ctr1) and the organic cation transporters (OCT-1/2). Complex 11 was accumulated preferentially via the organic cation transporters and by Na(+)/K(+)-dependent endocytosis. The new gold carbene complexes seem to operate by a mechanism different from that of the parent 1-methylimidazolium ligands.

Carbene iridium complexes for efficient water oxidation: scope and mechanistic insights

Iridium complexes of Cp* and mesoionic carbene ligands were synthesized and evaluated as potential water oxidation catalysts using cerium(IV) ammonium nitrate as a chemical oxidant. Performance was evaluated by turnover frequency at 50% conversion and by absolute turnover number, and the most promising precatalysts were studied further. Molecular turnover frequencies varied from 190 to 451 per hour with a maximum turnover number of 38 000. While the rate of oxygen evolution depends linearly on iridium concentration, concurrent spectroscopic and manometric observations following stoichiometric oxidant additions suggest oxygen evolution is limited by two sequential first-order reactions. Under the applied conditions, the oxygen evolving species appears to be a well-defined and molecular species based on kinetic analyses, effects of careful ligand design, reproducibility, and the absence of persistent dynamic light scattering signals. Outside of these conditions, the complex mechanism is highly dependent on reaction conditions. While confident characterization of the catalytically active species is difficult, especially under high-turnover conditions, this work strongly suggests the primary active species under these conditions is a molecular species.

Oxali‐Titanocene Y: A Potent Anticancer Drug

Outside of platinum and ruthenium anticancer drugs, there is significant unexplored space for further metal-based drugs that target cancer, such as titanocene dichloride. One of these promising drug candidates is bis-[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride (titanocene Y, 1), which is accessible via the hydridolithiation reaction of 6-anisylfulvene and subsequent transmetallation with titanium tetrachloride. Compound 1 exhibits an IC50 value of 21 mm toward the LLC-PK cell line, which has proven to be a good mimic of a kidney carcinoma cell line and a reliable tool for the optimisation of titanocenes against this type of cancer. Additionally, the antiproliferative activity of 1 and other titanocenes has been studied in 36 human tumour cell lines and against explanted human tumours. 6] These in vitro and ex vivo experiments showed that renal cell cancer is the prime target for this novel class of titanocenes, but there is significant activity against ovarian, prostate, cervical, lung, colon, and breast cancers as well. Furthermore, titanocene derivatives give a positive immune response by up-regulating the number of natural killer (NK) cells in mice. These results were underscored by initial mechanistic studies of the effects of these titanocenes on apoptosis and the apoptotic pathway in prostate and cervical cancer cells. Recently, animal studies demonstrated the successful treatment of mice bearing xenografted A431, Caki-1, and MCF-7 tumours with 1. Herein the synthesis and initial cytotoxicity studies of titanocene oxalate and oxali-titanocene Y (2) are presented. The structures and syntheses of 1 and 2 are shown in Scheme 1. A simple anion-exchange reaction in THF employing silver oxalate eliminates insoluble silver chloride and produces 2 or titanocene oxalate. An X-ray crystallographic study established the molecular structure of 2 (Figure 1). Despite the addition of the oxalate bidentate ligand in replacement of the two chlorides on the titanium centre, there is almost no apparent variance in the molecular structures of 1 and 2. The length of the bond between the titanium centre and the carbon atoms of the cyclopentadienide rings are very similar for both 1 and 2. They vary from 2.34 to 2.41 C for 1 and from 2.33 to 2.40 C for 2. Very slight differences can be observed in comparing the titanium centroid distances in 1 (2.06 C) and 2 (2.04 C). The centroid–titanium–centroid angle is 130.78 for 1, whereas the corresponding angle in 2 is 134.88. This widening goes nicely with the more blade-like shape of the oxalate anion, compared with the spherical chloride anions. As expected, the average titanium–chloride bond in 1 is considerably longer (2.37 C) than the average titanium–oxygen bond in 2 (1.99 C). The average carbon–oxygen single and double bonds in 2 are, with 1.30 C and 1.21 C, quite close to those found in free carboxylic acids, showing that there is very little, if any, negative charge located on the oxygen atoms that are not bonded to titanium. In 1 the chloride–titanium–chloride angle is 95.98, which is in the range of other titanocene dichlorides. In 1, however, the oxygen atoms are part of a chelate ring which forces the oxygen–titanium–oxygen angle to 79.08. Despite the addition of the bidentate oxalate ligand. minimal structural change incurred. In tests against LLC-PK cells, which have proven to be a valuable in vitro model for kidney cancer, titanocene oxalate shows an IC50 value of 140 mm, which is a significant improvement (14-fold) relative to titanocene dichloride, with an IC50 value of 2000 mm. Similar behaviour is observed for the p-dimethoxybenzyl-substituted species; 2 is 13-fold more cytotoxic against LLC-PK than 1 and exhibits an IC50 value of 1.6 mm (see Figure 2), which is twice as cytotoxic as cisplatin (3.3 mm). The Scheme 1. Structures and syntheses of titanocene Y (1) and oxali-titanocene Y (2): a) 2LiBEt3H, Et2O, 2BEt3 ; b) TiCl4, THF, 2LiCl(s) ; c) Ag2C2O4, THF, 2AgCl(s).

Molecular Dials: Hindered Rotations in Mono- and Diferrocenyl Anthracenes and Triptycenes

The syntheses, X-ray crystal structures, and molecular dynamics of 9-ferrocenylanthracene, 3, 9,10-diferrocenylanthracene, 4, 9-ferrocenyltriptycene, 7, and 9,10-diferrocenyltriptycene, 8, are reported. At 193 K, 3 exhibits C(s) symmetry via oscillation of the ferrocenyl only about the anthracene plane; at higher temperatures, complete rotation about the C(9)-ferrocenyl linkage becomes evident with a barrier of 10.6 kcal mol(-1). At 193 K, the ferrocenyls in 4 give rise to syn (C(2v)) and anti (C(2h)) rotamers that also interconvert at room temperature. In the corresponding triptycyl systems, 7 and 8, these rotational barriers increase to 17 kcal mol(-1); 9,10-diferrocenyltriptycene exists as slowly interconverting meso and racemic rotamers, in which the ferrocenyl moieties are, respectively, eclipsed (C(2v)) or staggered (C2). 2D-EXSY NMR data recorded with different mixing times indicate clearly that these interconversions proceed in a stepwise manner, for example, rac→meso→rac, thus behaving as a set of molecular dials.