Iridium complexes of dehydroamino acids: The kinetic resolution of racemic diphosphines and their application in catalytic asymmetric hydrogenation

The reaction of chiral diphosphines with a configurationally pure cationic bis-enamide complex of iridium, bis(menthyl (Z)-α-benzamidocinnamate)-iridium tetrafluoroborate, is described. When the reactant ligand is racemic then kinetic resolution occurs with high specificity under the appropriate conditions. Since the iridium diphosphine complex is catalytically inactive in homogeneous hydrogenation, the residual enantiomer may be reacted with bis(norbornadiene)-rhodium tetrafluoroborate to produce an active catalyst. This effects the hydrogenation of methyl (Z)-α-acetamidocinnamate in optical yields comparable with those obtained separately with the enantiomerically pure ligand rhodium complex. The reaction of pure (+)- or (-)-enantiomer of bis(menthyl (Z)-α-benzamidocinnamate)-iridium tetrafluoroborate with enantiomerically pure diphosphines has been studied. Invariably one hand of the diphosphine reacts rapidly with a given enantiomer of the iridium complex to give a stable diphosphine iridium enamide complex in which the original configuration of the coordinated olefin is maintained. The other combination of enantiomers reacts much more slowly, in keeping with the kinetic resolution work, and produces an enamide complex which is unstable in solution, isomerising to a second diastereomer. Since the absolute configuration of the iridium bis-enamide complex has been established by X-ray crystallography, this experiment affords a method of determining the configuration of rhodium enamide complexes in asymmetric hydrogenation (assuming structural homology between Rh and Ir). In all cases the disfavoured enamide complex was the one involved in the catalytic pathway.     

Tripodal oxygen and tripodal nitrogen ligands in hydroformylation reactions: formation of novel rhodium(III) carbonyl bis(acyl) complexes

The rhodium(I) complexes TpmsRh(CO)₂ (1) and TpmsRh(cod) (2) of the tripodal nitrogen ligand tris(pyrazolyl)methanesulfonate, Tpms⁻=[(pz)₃CSO₃]⁻, catalyze the hydroformylation of 1-hexene. Addition of phosphine has a negative effect on the activity. The hydroformylation activity reaches a maximum at about 60 °C. At temperatures above 80 °C hydrogenation becomes an important secondary reaction. When the catalysis is performed at 60 °C in acetone with 1 or 2 as catalyst precursor all of the rhodium is recovered in the form of the rhodium(III) bis(acyl) complex TpmsRh(CO)(COC₆H₁₃)₂ (9). A similar behaviour is observed with rhodium(I) complexes bearing the tripodal oxygen ligand L_OMe⁻=[(cyclopentadienyl)tris(dimethylphosphito-P) cobalt O,O^′,O″]⁻. In this case all of the rhodium is transformed into L_OMeRh(CO)(COC₆H₁₃)₂ (10). These hitherto unknown bis(acyl) rhodium(III) complexes show the same catalytic activity as the rhodium(I) starting compounds.     

Synthesis of rhodium(III), iridium(III) and osmium(III) complexes with tris(2-aminoethanethiolato)cobalt(III)

Polynuclear sulfur bridged complexes where the neutral complex tris(2-aminoethanethiolato)cobalt(III) acts as a tridentate ligand to rhodium(III), iridium(III) and osmium(III) have been prepared. These complexes have been characterized by electronic spectroscopy, vibrational spectroscopy and nuclear magnetic resonance spectroscopy. Along with the previously prepared complexes of iron(III), ruthenium(III) and cobalt(III), these complexes form two series of complexes with the group 8 and group 9 elements from all three transition series.     

Prochelators triggered by hydrogen peroxide provide hexadentate iron coordination to impede oxidative stress

Prochelators are agents that have little affinity for metal ions until they undergo a chemical conversion. Three new aryl boronate prochelators are presented that are responsive to hydrogen peroxide to provide hexadentate ligands for chelating metal ions. TRENBSIM (tris[(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylidene)-2-aminoethyl]amine), TRENBSAM (tris[(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl)-2-aminoethyl]amine), and TB (tris[(2-boronic acid-benzyl)2-aminoethyl]amine) convert to TRENSIM (tris[(salicylideneamino)ethyl]amine), TRENSAM (tris[(2-hydroxybenzoyl)-2-aminoethyl]amine), and TS (tris[2-hydroxybenzyl)2-aminoethyl]amine), respectively. The prochelators were characterized by ¹¹B NMR, and the structures of TRENBSAM, TRENBSIM, and the Fe(III) complex of TS were determined by X-ray crystallography. Of the three prochelator/chelator pairs, TB/TS was identified as the most promising for biological applications, as they prevent iron and copper-induced hydroxyl radical generation in an in vitro assay. TB has negligible interactions with metal ions, whereas TS has apparent binding constants (log K′) at pH 7.4 of 15.87 for Cu(II), 9.67 Zn(II) and 14.42 for Fe(III). Up to 1 mM TB was nontoxic to retinal pigment epithelial cells, whereas 10 μM TS induced cell death. TS protected cells against H₂O₂-induced death, but only within a 1-10 μM range. TB, on the other hand, had a much broader window of protection, suggesting that it may be a useful agent for preventing metal-promoted oxidative damage.     

Mononuclear rhodium and iridium compounds with pyridyl-pyrazole ligands

Neutral [MCl(L₂)(Hpzpy)], [M(L₂)(pzpy)] and cationic [M(L₂)(Hpzpy)]CF₃SO₃ rhodium(I) or iridium(I) complexes [M = Rh or Ir; L₂ = diolefin or (CO)₂; pzpy = 3-(2-pyridyl)pyrazolate] have been prepared; the pzpy and Hpzpy ligands coordinate to the metal as bidentate chelate groups through one pyrazole nitrogen and the pyridine nitrogen atom. The reactivity of these complexes towards oxidative addition reactions of halogens, methyl iodide or triflic acid and towards displacement reactions has been studied. The neutral and cationic iridium(I) complexes are modest catalysts for the hydrosilylation of phenylacetylene with triethylsilane at 60 °C. The complexes have been characterised by analytical and spectroscopic data; their configuration has been confirmed by COSY and NOESY experiments and the molecular structure of [Rh(COD)(Mepzpy)(PPh₃)]CF₃SO₃ has been established by an X-ray diffraction study.     

A highly enantioselective rhodium catalyst for the hydrogenation of aliphatic α-keto esters

The enantioselective hydrogenation of several α-keto acid derivatives with rhodium diphosphine catalysts has been investigated using a random screening approach. The neutral rhodium catalyst prepared in situ from bis(2,5-norbornadiene rhodium chloride) and NORPHOS has been found to be an excellent catalyst for preparing aliphatic α-hydroxy esters in high optical purities. The reaction parameters for the hydrogenation of ethyl 2-oxo-4-phenyl-butyrate, an intermediate for the ACE inhibitor Benazepril, were optimized and the best optical yields obtained were 96%.     

Synthesis and biological properties of the lipophilic technetium-99m complex 99mTc(acac)3

In the development of technetium-99m radiopharmaceuticals for the evaluation of regional cerebral perfusion, one series of complexes that has remained unexplored is the neutral lipophilic tris complexes formed with β-diketonato ligands. The prototype complex of this series, tris(2,4-pentanedionato) technetium(III), has been prepared via a new synthetic route and chemically characterized using ⁹⁹Tc and the biodistribution of the no-carrier-added ^99mTc complex has been determined. The ^99mTc complex was found to be distributed throughout the body with persistant high blood levels indicative of a high degree of protein binding. The primary route of excretion was the hepatobiliary system as indicated by the appearance of ^99mTc in the gut and feces at longer sample times post-injection. Although this complex was not retained by the brain, it does provide a starting point from which a more effective agent might be developed.     

Enhancing and inhibiting effects of benzenediols on chemiluminescence of a novel cyclometallated iridium(III) complex

A novel chemiluminescence (CL) system, including the cyclometallated iridium(III) complex {tris[1‐(2,6‐dimethylphenoxy)‐4‐(4‐chlorophenyl)phthalazine]iridium}, potassium permanganate and oxalic acid, is proposed for the determination of benzenediols. This method is based on the fact that hydroquinone and catechol exhibited an inhibiting effect, while resorcinol exhibited an enhancing effect on CL intensity. The optimum conditions for CL emission were investigated. Under optimal conditions, the detection limits of hydroquinone, catechol and resorcinol were 6.4 × 10^?8, 2.7 × 10^?9 and 8.1 × 10^?7 mol/L, respectively. The method has been successfully applied to the determination of benzenediols in different types of water sample. The luminophors of the CL systems were all identified as the metal–ligand charge‐transfer (MLCT) excited state of the iridium complex. Copyright © 2011 John Wiley & Sons, Ltd.     

Thermostable enzymes for industrial applications

Summary The variety of thermostable (TS) enzymes has been steadily increasing for use in industrial applications, mainly as replacements for thermolabile (TL) enzymes. For example, TS amylases fromBacillus licheniformis andBacillus stearothermophilus have replaced TL amylases fromBacillus subtilis. TS enzymes also have advantages in new areas such as cyclodextrin production. The TS cyclodextrin glycosyl transferase (CGTase) fromThermoanaerobacter sp. (95°C optimum) gives a higher productivity than the CGTase fromBacillus macerans (55°C optimum). In the area of enzymatic bleach boosting of wood pulps, a TS xylanase (Myceliophera thermophila) would be advantageous over a TL xylanase (Trichoderma reesei), due to the high temperature of the incoming pulp. Not all TS enzymes are from thermophiles; the mesophileCandida antarctica produces a TS lipase which has a temperature optimum of 90°C when immobilized. The characterization of these enzymes will be described along with comparisons to some newly described TS enzymes.     

Dehydrogenation of alkanes catalyzed by an iridium phosphinito PCP pincer complex

The novel phosphinito iridium PCP pincer complex, IrH₄{C₆H₃-2,6-(OPPrⁱ₂)₂} can be conveniently synthesized and isolated in 74% overall yield. The complex catalyzes the dehydrogenation of linear alkanes to alkenes at the rate of 13 turnovers min⁻¹ at 200 °C. This catalytic activity is slightly higher than that exhibited by iridium complexes of analogous bis(phosphino) PCP ligands. The bis(phosphinito) complex is resistant to decomposition for periods up to 7 days at temperatures as high as 200 °C thus matching the thermal stability of the bis(phosphino) pincer complexes.     

Equilibrium, solid state behavior and reactions of four and five co-ordinate carbonyl stibine complexes of rhodium. Crystal Structures of trans-[Rh(Cl)(CO)(SbPh3)2], trans-[Rh(Cl)(CO)(SbPh3)3] and trans-[Rh(I)2(CH3)(CO)(SbPh3)2]

The crystal structures of the four-coordinate trans-[Rh(Cl)(CO)(SbPh₃)₂] (1) and the five-coordinate trans-[Rh(Cl)(CO)(SbPh₃)₃] (2) are reported, as well as the unexpected oxidative addition product, trans-[Rh(I)₂(CH₃)(CO)(SbPh₃)₂] (3), obtained from the reaction of 2 with CH₃I. The formation constants of the five-coordinate complex were determined in dichloromethane, benzene, diethyl ether, acetone and ethyl acetate as 163±8, 363±10, 744±34, 1043±95 and 1261±96 M⁻¹, respectively. While coordinating solvents facilitate the formation of the five-coordinate complex, the four-coordinate complex could be obtained from diethyl ether due to the favorable low crystallization energy. The tendency of stibine ligands to form five-coordinate rhodium(I) complexes is attributed mainly to electron deficient metal centers in these systems, with smaller contributions by the steric effects. The average effective cone angle for the SbPh₃ ligand in the three crystallographic studies was determined as 139° with individual values ranging from 133 to 145°.     

The search for new hydrogenation catalyst motifs based on N-heterocyclic carbene ligands

A series of new iridium complexes containing N-heterocyclic carbene ligands (NHCs) has been prepared and tested for hydrogenation of primary (1-octene), secondary (cyclohexene), tertiary (1-methylcyclohexene) and quartenary (2,3-dimethyl-2-butene) alkenes. Taking inspiration from Crabtree’s catalyst, [Ir(COD)(PCy₃)(py)]PF₆, the labile pyridine ligand was exchanged with an NHC ligand, and was found to produce catalysts with similar activities and rates. Further refinement of the ligands produced the optimal version of the iridium phosphine/NHC combination: Using a smaller phosphine, tri-n-butylphosphine, a saturated NHC and the non-coordinating anion, tetrakis(3,5-bis(trifluoromethylphenyl))borate (BARF), a highly active catalyst that has substantially better longevity and stability, but similar activity, to the parent Crabtree’s catalyst was prepared in three steps. The effect of the BARF counteranion was explored, and was shown to improve even Crabtree’s catalyst, and is thus a general phenomenon for iridium catalysts in non-polar solvents. Mechanistic studies suggest that the catalyst resting state is a dimeric complex, presumably hydride-bridged, that dissociates into catalytically active species under catalytic conditions. Thus, the catalyst dead-end for Crabtree’s catalyst, hydride-bridged dimers and trimers, may in fact be a reversible resting state for the iridium complexes described here.     

Chemiluminescence of a cyclometallated iridium(III) complex and its application in the detection of cysteine

Chemiluminescence (CL) of a cyclometallated iridium (III) complex {tris[1‐(2,6‐dimethylphenoxy)‐4‐(4‐chlorophenyl)phthalazine]iridium(III)} in the presence of potassium permanganate and oxalic acid is reported for the first time. Cysteine exhibits sufficient enhancing effect on the CL generated from the cyclometallated iridium(III) complex, which make it possible for the sensitive detection of cysteine using a flow‐injection–chemiluminescence (FI–CL) method. The optimum conditions for the chemiluminescence emission were investigated. Under the optimal condition, the linear range for the determination of cysteine was 1.0 × 10^–9–5.0 × 10^–6 mol/L with a detection limit of 6.9 × 10^–10 mol/L. A relative standard deviation of 1.6% was obtained for eight replicate determinations. The mechanisms of CL are proposed and the emitting species was identified as the metal‐to‐ligand charge‐transfer (MLCT) excited states of the iridium complex. Copyright © 2011 John Wiley & Sons, Ltd.     

Recognition of G-U mismatches by tris(4,7-diphenyl-1,10-phenanthroline)rhodium(III).

The coordination complex tris(4,7-diphenyl-1,10-phenanthroline)rhodium(III) [Rh(DIP)3(3+)], which promotes RNA cleavage upon photoactivation, has been shown to target specifically guanine-uracil (G-U) mismatches in double-helical regions of folded RNAs. Photoactivated cleavage by Rh(DIP)3(3+) has been examined on a series of RNAs that contain G-U mismatches, yeast tRNA(Phe) and yeast tRNA(Asp), as well as on 5S rRNAs from Xenopus oocytes and Escherichia coli. In addition, a "microhelix" was synthesized, which consists of seven base pairs of the acceptor stem of yeast tRNA(Phe) connected by a six-nucleotide loop and contains a mismatch involving residues G4 and U69. A U4.G69 variant of this sequence was also constructed, and cleavage by Rh(DIP)3(3+) was examined. In each of these cases, specific cleavage is observed at the residue which lies to the 3'-side of the wobble-paired U; some cleavage by the rhodium complex is also evident in several structured RNA loops. The remarkable site selectivity for G-U mismatches within double-helical regions is attributed to shape-selective binding by the rhodium complex. This binding furthermore depends upon the orientation of the G-U mismatch, which produces different stacking interactions between the G-U base pair with the Watson-Crick base pair following it on the 5'-side of U compared to the Watson-Crick pair preceding it on the 3'-side of U. Rh(DIP)3(3+) therefore serves as a unique probe of G-U mismatches and may be useful both as a model and in probing RNA-protein interactions as well as in identifying G-U mismatches within double-helical regions of folded RNAs.     

Ultrastructure of the spermatozoon of Anomotaenia quelea (Mettrick, 1961) (Cestoda,Cyclophyllidea, Dilepididae), an intestinal parasite of Quelea quelea (Aves,Ploceidae) in Senegal

The mature spermatozoon of Anomotaenia quelea exhibits an apical cone of electron-dense material and two helicoidal crest-like bodies. The apical cone near its base is surrounded by a lucent cytoplasm and a spiraled layer of cortical microtubules. The crest-like bodies are of different lengths, spiraled and make an angle of 30–40° to the hypothetical spermatozoon axis. The axoneme is of the 9 + ‘1’ trepaxonematan pattern and is surrounded by a periaxonemal sheath of electron-dense material. The cytoplasm contains in regions III and IV numerous electron-dense granules situated between the periaxonemal sheath and the cortical microtubules. The posterior extremity of the spermatozoon of A. quelea exhibits a nucleus and a disorganized axoneme and cortical microtubules. This type of posterior extremity of the mature spermatozoon has never been described previously in a Dilepididae. Similarly, two crest-like bodies have not been observed before in a dilepidid cestode.     

Preparation of anti-2,4-dichlorophenol and 2,4-dichlorophenoxyacetic acid monoclonal antibodies

The ratios of hapten and bovine serum albumin (BSA) in an antigen conjugate were determined by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Hybridomas secreting monoclonal antibodies against 2,4-dichlorophenoxyacetic acid (2,4-D) were produced by fusing 2,4-D-BSA conjugate-immunized splenocytes with a HAT-sensitive mouse myeloma cell line, P3-X63-Ag8-653. A substantial cross-reaction was observed for 2,4-dichlorophenol (2,4-DP) when compared with that observed for 2,4-D. The full measurement range for this assay is 0.2–3 μg ml⁻¹ for 2,4-DP. On the other hand, the range for 2,4-D is between 1 and 20 μg ml⁻¹. This revised version was published online in July 2006 with corrections to the Cover Date.     

Determination of the Enantiomerization Barrier of the Residual Enantiomers of C3‐Symmetric Tris[3‐(1‐Methyl‐2‐Alkyl)Indolyl]Phosphane Oxides: Case Study of a Multitasking HPLC Investigation Based on an Immobilized Polysaccharide Stationary Phase

The residual enantiomers of three tris‐(3‐indolyl)‐phosphane oxides bearing different alkyl groups (methyl, ethyl or i‐propyl) in position 2 of the indole rings constituting the blades were separated on the immobilized type Chiralpak IC column in polar organic and reversed‐phase modes. The good enantioselectivity and versatility of the IC CSP allowed easy isolation of the enantiomerically highly enriched samples suitable for configurational stability studies. The enantiomerization barriers of residual phosphane oxides were evaluated both by off‐column techniques (CD signal and enantiomeric purity decay kinetics) and by dynamic enantioselective high‐performance liquid chromatography (HPLC). Chirality 27:888–899, 2015. © 2015 Wiley Periodicals, Inc.     

Synthesis and chiroptical properties of organometallic complexes of helicenic N‐heterocyclic carbenes

Novel [4, 6]helicenes ( 4a,b ) bearing a fused imidazolium unit have been prepared from [4, 6]helicene‐2,3‐di‐n‐propyl‐amines 3a,b . The in situ formation of N‐heterocyclic carbene (NHC) derivatives followed by their complexation to iridium(I) or rhodium(I) gave access to complexes 1a , 1′a , and 1b , containing mono‐coordinated helicene‐NHC, chloro and COD (COD = 1,5‐cyclooctadiene) ligands. Ir and Rh complexes 1a and 1′a were characterized by X‐ray crystallography. HPLC and NMR analyses showed that Ir(I) complex 1b existed as a mixture of two diastereomeric complexes corresponding to enantiomeric pairs M‐(?)/P‐(+)‐ 1b ¹ and M‐(?)/P‐(+)‐ 1b ² which differ by the position of COD through space. The chiroptical properties (electronic circular dichroism and optical rotation) of the four stereoisomers were measured. These complexes were also tested as catalysts in a transfer hydrogenation reaction.     

Reaction of a bulky phosphite with [Ru3(CO)12]: The molecular structure of one of the decomposition products

Mono- and bis-substituted phosphite complexes [Ru₃(CO)_12−x L_x] (L = tris(2,4-di-tert-butylphenyl) phosphite; x = 1, 2) were synthesized by simple substitution reactions, and were characterized by spectroscopic methods. The monosubstituted ruthenium complex disproportionates in acetone producing a mononuclear ruthenium complex as one of the decomposition products. Single crystal X-ray diffraction analysis established the molecular structure of this new compound.     

Novel α-pinene-derived mono- and bisphosphinite ligands: Synthesis and application in catalytic hydrogenation

Novel mono- and bisphosphinite (−)-pinane-based ligands have been synthesized from (−)-α-pinene. Mixed with [(COD)₂Rh]⁺[BF₄]⁻, these ligands displayed moderate up to high catalytic activity in hydrogenation of dimethyl itaconate with dihydrogen. It has been observed that the structure of the ligand, the reaction temperature and solvent are important to define productivity of the phosphinite-based Rh-catalysts. Bisphosphinite ligands in hydrogenation reactions suffered from an Arbuzov rearrangement, leading to fast deactivation of the hydrogenation catalyst. In contrast, monophosphinite-derived Rh-catalysts showed increased productivity as well as thermal stability. An almost quantitative conversion of dimethyl itaconate has been achieved at elevated temperatures in toluene. Alternatively, hydrogenation of dimethyl itaconate with monophosphinite ligands has been carried out in MeOH at room temperature or 40 °C and has led to a nearly quantitative conversion.