Gene Doping Control Analysis of Human Erythropoietin Transgene in Equine Plasma by PCR-Liquid Chromatography High-Resolution Tandem Mass Spectrometry.

Gene doping involves the misuse of genetic materials to alter an athlete's performance, which is banned at all times in both human and equine sports. Quantitative polymerase chain reaction (qPCR) assays have been used to control the misuse of transgenes in equine sports. Our laboratory recently developed and implemented duplex as well as multiplex qPCR assays for transgenes detection. To further advance gene doping control, we have developed for the first time a sensitive and definitive PCR-liquid chromatography high-resolution tandem mass spectrometry (PCR-LC-HRMS/MS) method for transgene detection with an estimated limit of detection of below 100 copies/mL for the human erythropoietin (hEPO) transgene in equine plasma. The method involved magnetic-glass-particle-based extraction of DNA from equine plasma prior to PCR amplification with 2'-deoxyuridine 5'-triphosphate (dUTP) followed by treatments with uracil DNA glycosylase and hot piperidine for selective cleavage to give small oligonucleotide fragments. The resulting DNA fragments were then analyzed by LC-HRMS/MS. The applicability of this method has been demonstrated by the successful detection of hEPO transgene in a blood sample collected from a gelding (castrated male horse) that had been administered the transgene. This novel approach not only serves as a complementary method for transgene detection but also paves the way for developing a generic PCR-LC-HRMS/MS method for the detection of multiple transgenes.

Identification of erythropoietin mimetic peptide 1 linear form in a sealed vial and its administration study in horses for doping control purpose.

The erythropoietin mimetic peptide 1 linear form (EMP1-linear), GGTYSCHFGPLTWVCKPQGG-NH2 , was identified in an unknown preparation consisting of white crystalline powder contained in sealed glass vials using ultrahigh performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). The white crystalline powder, allegedly used for doping racehorses, was found to contain around 2% (w/w) of EMP1-linear. EMP1-linear can be cyclised in equine plasma at physiological temperature of 37°C by forming an intramolecular disulfide bond to give EMP1, which is a well-known erythropoiesis stimulating agent that can bind to and activate the receptor for cytokine erythropoietin (EPO). Thus, EMP1-linear is a prodrug of EMP1, which is a performance-enhancing doping agent that can be misused in equine sports. In order to identify potential target(s) for detecting the misuse of EMP1-linear in horses, an in vitro metabolic study using horse liver S9 fraction was performed. After incubation, EMP1-linear mainly existed in its cyclic form as EMP1, and four N-terminus truncated in vitro metabolites TYSCHFGPLTWVCKPQGG-NH2 (M1), SCHFGPLTWVCKPQGG-NH2 (M2), WVCKPQGG-NH2 (M3) and VCKPQGG-NH2 (M4) were identified. An intravenous administration study with the preparation of white crystalline powder containing EMP1-linear was also conducted using three retired thoroughbred geldings. EMP1 was detectable only in the postadministration plasma samples, whereas the four identified in vitro metabolites were detected in both postadministration plasma and urine samples. For controlling the misuse of EMP1-linear in horse, its metabolite M3 gave the longest detection time in both plasma and urine and could be detected for up to 4 and 27 h postadministration, respectively.

Hydrodeoxygenative Coupling and Transformation of Aldehydes at a N2-Derived Tetranuclear Titanium Imide/Hydride Framework.

Carbon-carbon bond formation via coupling of two organic components is among the most important chemical transformations in organic synthesis. Herein, we report an unprecedented hydrodeoxygenative coupling of aromatic aldehydes to form bibenzyls by a N2-derived tetranuclear titanium imide/hydride complex [(Cp'Ti)4(µ3-NH)2(µ-H)4] (1; Cp' = C5Me4SiMe3). Further reactions with the corresponding aldehydes under air afford hydrobenzamides together with a titanium oxo complex. Both hydride and imide ligands play an important role for the reductive coupling, hydrogenation processes, as well as the functionalization of the N2-derived imide units without the need of sacrificial reagents. These results demonstrate that the tetranuclear titanium imide/hydride framework is not only applicable for N2 activation and functionalization but also providing a new platform for the C-C bond formation using carbonyl compounds.

Flexible Coordination of the Bis(amino-oxazoline) Ligand in Rare-Earth Metal Complexes: Synthesis, Structure, and Their Reactivity and Polymerization Performance.

Mononuclear rare-earth metal alkyl complexes supported by tetradentate dianionic bis(amino-oxazoline) ligands have been synthesized, and their reactivity toward small molecules and catalytic performance on ring-opening polymerization have been studied. Treatment of Ln(CH2SiMe3)3(THF)2 (Ln = Sc, Y; THF = tetrahydrofuran) with the bis(amino-oxazoline) proligand H2L afforded the corresponding rare-earth metal monoalkyl complexes L-Ln(CH2SiMe3)(THF)x (Ln = Sc, x = 0 (1); Ln = Y, x = 1 (2)). The isopropyl-substituted Sc alkyl complex L'-Sc(CH2SiMe3) (3) and the analogue Y silylamide complex L-Y[N(SiHMe2)2] (4) have been prepared by a similar method. Complexes 1 and 2 were stable in solution at room temperature but transformed gradually at elevated temperature to give a nucleophilic addition product for Sc (5) and an oxazoline ring-opened dimeric complex for Y (6). Reactions of 1 with elemental sulfur and selenium each led to insertion of one chalcogen into the Sc-C bond, and the corresponding six-coordinate mononuclear chalcogenolate complexes L-Sc(ECH2SiMe3)(THF) (E = S (7), Se (8)) were isolated. Treatment of 1 with an equimolar amount of aniline yielded the Sc anilide complex L-Sc(NHC6H5) (9), whereas the reaction of 1 with [NHEt3][BPh4] afforded the Sc ion-pair [L-Sc][BPh4] (10), which upon recrystallization led to formation of a THF-solvated product [L-Sc(THF)][BPh4] (11). Single-crystal X-ray diffraction analyses of complexes 1-3, 7-9, and 11 revealed the flexible coordination capability of the tetradentate bis(amino-oxazoline) ligand of upholding a mononuclear metal center via a torsion of the diaminobiphenyl axis. Complexes 1-4 were active catalysts for initiating the ring-opening polymerization of rac-lactide with good activity (TOF up to 3204 h-1) and heteroselectivity (Pr = 0.65-0.71). This study highlights the applicability of the well-defined tetradentate bis(amino-oxazoline) ligands for mononuclear rare-earth metal complexation and shed light on the new potential of rare-earth metal catalysts bearing this type of easily derivatizable polydentate ligand.

Long-term monitoring of IOX4 in horse hair and its longitudinal distribution with segmental analysis using liquid chromatography/electrospray ionization Q Exactive high-resolution mass spectrometry for the purpose of doping control.

IOX4, a hypoxia-inducible factor stabilizer, is classified as a banned substance for horses in both horse racing and equestrian sports. We recently reported the pharmacokinetic profiles of IOX4 in horse plasma and urine and also identified potential monitoring targets for the doping control purpose. In this study, a long-term longitudinal analysis of IOX4 in horse hair after a nasoesophageal administration of IOX4 (500 mg/day for 3 days) to three thoroughbred mares is presented for the first time for controlling the abuse/misuse of IOX4. Six bunches of mane hair were collected at 0 (pre), 1, 2, 3, and 6 month(s) postadministration. Our results showed that the presence of IOX4 was identified in all postadministration horse hair samples, but no metabolite could be detected. The detection window for IOX4 could achieve up to 6-month postadministration (last sampling point) by monitoring IOX4 in hair. In order to evaluate the longitudinal distribution of IOX4 over 6 months, a validated quantification method of IOX4 in hair was developed for the analysis of the postadministration samples. Segmental analysis of 2-cm cut hair across the entire length of postadministration hair showed that IOX4 could be quantified up to the level of 1.84 pg/mg. In addition, it was found that the movement of the incorporated IOX4 band in the hair shaft over 6 months varied among the three horses due to individual variation and a significant diffusion of IOX4 band up to 10 cm width was also observed in the 6-month postadministration hair samples.

Rare-Earth-Metal Complexes Bearing an Iminodibenzyl-PNP Pincer Ligand: Synthesis and Reactivity toward 3,4-Selective Polymerization of 1,3-Dienes.

A PNP-pincer ligand provides a versatile ligation framework, which is highly useful in organometallic chemistry and catalytic chemistry. In this work, by a de novo strategy, a simple and efficient synthetic pathway, has been developed to prepare the new iminodibenzyl-based PNP pincer proligand imin-RPNP(Li or H) (R = isopropyl, phenyl). By employing salt metathesis or direct alkyl elimination, we successfully synthesized a series of iminodibenzyl-PNP rare-earth-metal (Ln = Sc, Y, Dy, Ho, Er, Tm, Lu) complexes and characterized them by NMR and X-ray diffraction analyses. Upon addition of a borate and triisobutylaluminum (TIBA), the rare-earth-metal complexes 2-Y, 2-Dy, 2-Ho, 2-Er, and 2-Tm bearing the imin-PhPNP ligand exhibited unexpectedly high 3,4-selectivity (up to 95%) for the polymerization of 1,3-dienes (isoprene and myrcene); in particular, the chosen yttrium complex 2-Y promoted the 1,3-diene polymerization in a living manner. A computational study suggested that the sterically congested configuration around the metal center imposed by the imin-RPNP ligand might be the main reason for this unusual selectivity.

Access to Derivatizable Octahydrofluorenyl Ligand: Half-Sandwich Rare-Earth Metal Complexes for Highly Syndiospecific (Co)Polymerization of Styrene.

A simple and facile synthetic pathway for accessing new derivatizable bulky-demanding octahydrofluorenyl (OHF) ligands has been developed, and a series of half-sandwich rare-earth metal (Sc, Y, Lu) complexes bearing the OHF ancillary ligands have been synthesized. In conjunction with a borate, the OHF-ligated Sc complexes exhibited high catalytic activity for styrene (co)polymerization to afford polymers with highly syndiotactic polystyrene sequence (>99% rrrr).

Comprehensive metabolic study of IOX4 in equine urine and plasma using liquid chromatography/electrospray ionization Q Exactive high-resolution mass spectrometer for the purpose of doping control.

IOX4 is a hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitor, which was developed for the treatment of anemia by exerting hematopoietic effects. The administration of HIF-PHD inhibitors such as IOX4 to horses is strictly prohibited by the International Federation of Horseracing Authorities and the Fédération Équestre Internationale. To the best of our knowledge, this is the first comprehensive metabolic study of IOX4 in horse plasma and urine after a nasoesophageal administration of IOX4 (500 mg/day, 3 days). A total of four metabolites (three mono-hydroxylated IOX4 and one IOX4 glucuronide) were detected from the in vitro study using homogenized horse liver. As for the in vivo study, post-administration plasma and urine samples were comprehensively analyzed with liquid chromatography/electrospray ionization high-resolution mass spectrometry to identify potential metabolites and determine their corresponding detection times. A total of 10 metabolites (including IOX4 glucuronide, IOX4 glucoside, O-desbutyl IOX4, O-desbutyl IOX4 glucuronide, four mono-hydroxylated IOX4, N-oxidized IOX4, and N-oxidized IOX4 glucoside) were found in urine and three metabolites (glucuronide, glucoside, and O-desbutyl) in plasma. Thus, the respective quantification methods for the detection of free and conjugated IOX4 metabolites in urine and plasma with a biphase enzymatic hydrolysis were developed and applied to post-administration samples for the establishment of elimination profiles of IOX4. The detection times of total IOX4 in urine and plasma could be successfully prolonged to at least 312 h.

Oxidizing Cerium(IV) Alkoxide Complexes Supported by the Kläui Ligand [Co(η5-C5H5){P(O)(OEt)2}3]-: Synthesis, Structure, and Redox Reactivity.

Tetravalent cerium alkoxide complexes supported by the Kläui tripodal ligand [Co(η5-C5H5){P(O)(OEt)2}3]- (LOEt-) have been synthesized, and their nucleophilic and redox reactivity have been studied. Treatment of the Ce(IV) oxo complex [CeIV(LOEt)2(O)(H2O)]·MeCONH2 (1) with iPrOH or reaction of [CeIV(LOEt)2Cl2] (2) with Ag2O in iPrOH afforded the Ce(IV) dialkoxide complex [CeIV(LOEt)2(OiPr)2] (3-iPr). The methoxide and ethoxide analogues [CeIV(LOEt)2(OR)2] (R = Me (3-Me), Et (3-Et)) have been prepared similarly from 2 and Ag2O in ROH. Reaction of 3-iPr with an equimolar amount of 2 yielded a new Ce(IV) complex that was formulated as the chloro-alkoxide complex [CeIV(LOEt)2(OiPr)Cl] (4). Treatment of 3-iPr with HX and methyl triflate (MeOTf) afforded [Ce(LOEt)2X2] (X- = Cl-, NO3-, PhO-) and [CeIV(LOEt)2(OTf)2], respectively, whereas treatment with excess CO2 in hexane led to isolation of the Ce(IV) carbonate [CeIV(LOEt)2(CO3)]. 3-iPr reacted with water in hexane to give a Ce(III) complex and a Ce(IV) species, presumably the reported tetranuclear oxo cluster [CeIV4(LOEt)4(O)5(OH)2]. The Ce(IV) alkoxide complexes are capable of oxidizing substituted phenols, possibly via a proton-coupled electron transfer pathway. Treatment of 3-iPr with ArOH afforded the Ce(III) aryloxide complexes [CeIII(LOEt)2(OAr)] (Ar = 2,4,6-tri-tert-butylphenyl (5), 2,6-diphenylphenyl (6)). On the other hand, a Ce(III) complex containing a monodeprotonated 2,2'-biphenol ligand, [CeIII(LOEt)2(tBu4C12H4O2H)] (7) (tBu4C12H4O2H2 = 4,4',6,6'-tetra-tert-butyl-2,2'-biphenol), was isolated from the reaction of 3-iPr with 2,4-di-tert-butylphenol. The crystal structures of complexes 3-iPr, 3-Me, 3-Et, and 5-7 have been determined.

Unsymmetrical diarylamido-based rare-earth alkyl complexes: their synthesis and catalytic performance in isoprene polymerization.

A family of rare-earth complexes bearing diarylamido-based pincer ligands with phosphino-, phenylthio- and quinolino-sidearms have been synthesized and fully characterized. Upon activation by [Ph3C][B(C6F5)4], the scandium (P-Sc and S-Sc) and yttrium complexes (P-Y and S-Y) could catalyze the polymerization of isoprene with cis-1,4 selectivity (up to 98.8%), while the lutetium analogues P-Lu and S-Lu produced trans-1,4 selective polyisoprene (up to 83.3%). Density functional theory (DFT) calculations were carried out to clarify the mechanisms for the metal-dependent stereoselective (cis to trans) polymerization of isoprene catalyzed by P-Sc, P-Y and P-Lu, suggesting that kinetically and thermodynamically more favorable insertion-isomerization during chain propagation is the key reason for P-Lu catalyzed trans-stereoselective isoprene polymerization.

Rigid Acridane-Based Pincer Supported Rare-Earth Complexes for cis-1,4-Polymerization of 1,3-Conjugated Dienes.

A convenient synthetic route has been developed for preparing the novel rigid 4,5-(PR2)2-2,7,9,9-tetramethylacridane-based pincer ligands (acri-RPNP; R = iPr and Ph), and the first rare-earth (Ln = Y, Lu) alkyl complexes bearing the acri-RPNP ligands were synthesized by a salt metathesis reaction (for the isopropyl-substituent acri-iPrPNP complexes, 1-Ln) or direct alkylation (for the phenyl-substituent acri-PhPNP complexes, 2-Ln). For both 1-Ln and 2-Ln, the NMR spectroscopy and X-ray diffraction study confirmed the successful coordination of the acri-RPNP ligand to the central metal ion in a tridentate manner via the two phosphine and the nitrogen donors. In contrast to 1-Ln that are solvent-free complexes, the metal centers in 2-Ln are each coordinated with one tetrahydrofuran molecule. Upon activation by [Ph3C][B(C6F5)4], 1-Y and 2-Lu could catalyze the living polymerization of isoprene and ß-myrcene with high catalytic activity and high cis-1,4-selectivity (up to 92.3% for isoprene and 98.5% for ß-myrcene). Moreover, the 1-Y/[Ph3C][B(C6F5)4] catalytic system also could promote the polymerization of butadiene and its copolymerization with isoprene to produce copolymers with high cis-1,4-selectivity and narrow polydispersity.

Metabolic studies of selective androgen receptor modulators RAD140 and S-23 in horses.

This paper describes the studies of the in vitro biotransformation of two selective androgen receptor modulators (SARMs), namely, RAD140 and S-23, and the in vivo metabolism of RAD140 in horses using ultra-high performance liquid chromatography-high resolution mass spectrometry. in vitro metabolic studies of RAD140 and S-23 were performed using homogenised horse liver. The more prominent in vitro biotransformation pathways for RAD140 included hydrolysis, hydroxylation, glucuronidation and sulfation. Metabolic pathways for S-23 were similar to those for other arylpropionamide-based SARMs. The administration study of RAD140 was carried out using three retired thoroughbred geldings. RAD140 and the majority of the identified in vitro metabolites were detected in post-administration urine samples. For controlling the misuse of RAD140 in horses, RAD140 and its metabolite in sulfate form gave the longest detection time in hydrolysed urine and could be detected for up to 6 days post-administration. In plasma, RAD140 itself gave the longest detection time of up to 13 days. Apart from RAD140 glucuronide, the metabolites of RAD140 described herein have never been reported before.

Tiludronic acid can be detected in blood and urine samples from Thoroughbred racehorses over 3 years after last administration.

BACKGROUND: Administration of bisphosphonates, including tiludronic acid, to Thoroughbred racehorses below 3 and a half years of age is prohibited in most racing jurisdictions. OBJECTIVES: To determine if evidence of administration of tiludronic acid could be obtained from analysis of blood and urine samples beyond 40 days after administration. STUDY DESIGN: Retrospective cohort. METHODS: Horses maintained in a highly controlled environment and treated with Tildren®a were selected from clinical records. Twenty-four horses were identified, 21 of which were still in race training. Blood and urine samples were collected and analysed for the presence of tiludronic acid using ultra-high-performance liquid chromatography-high-resolution mass spectrometry. RESULTS: Tiludronic acid was detected in samples from every horse, including two that had been given a therapeutic dose of the drug 3 years prior to sample collection. The estimated concentrations of tiludronic acid in the blood collected at least 2 years post-administration were consistently very low (less than 0.3 ng/mL). The estimated concentrations in urine were less consistent and were generally lower than those in blood, although higher levels were inconsistently detected in individual horses (up to about 16 ng/mL almost 1 year post-administration in 1 horse and about 3.7 ng/mL at almost 3 years post-administration in another). MAIN LIMITATIONS: The study was performed in horses that are older than the primary target group. A single sample was obtained from most horses and so we cannot comment on elimination profiles. CONCLUSIONS: Evidence that a therapeutic dose of tiludronic acid has been administered to a horse can be obtained from detection of the drug in blood and urine samples over 3 years after it was administered.

4-Coordinated, 14-electron ruthenium(ii) chalcogenolate complexes: synthesis, electronic structure and reactions with PhICl2 and organic azides.

The 4-coordinated RuII chalcogenolate complexes [Ru(STipp)2(PPh3)2] (Tipp = 2,4,6-triisopropylphenyl, 1) and [Ru(SeMes)2(PPh3)2] (Mes = 2,4,6-trimethylphenyl, 2) have been synthesized, and their reactions with PhICl2 and organic azides have been studied. Complex 2 synthesized from [RuII(PPh3)3Cl2] and NaSeMes displays a seesaw structure with P-Ru-P and Se-Ru-Se bond angles of 103.43(13) and 145.26(6)°, respectively. Natural bond order analyses revealed that in each of 1 and 2, there are two n →σ* (donor-acceptor) π interactions between the chalcogen lone pairs and the Ru-P antibonding molecular orbitals. The calculated second-order perturbation interaction energies of the two interactions for 1 (20.5 and 18.3 kcal mol-1) are stronger than those of 2 (13.6 and 11.0 kcal mol-1), suggesting the thiolate ligand (TippS-) is a stronger π-donor than the selenolate ligand (MesSe-) with respect to RuII. Chlorination of 1 with PhICl2 afforded the dichloride complex [Ru(STipp)2Cl2(PPh3)] (3), which was hydrolyzed to the hydroxo complex [Ru(STipp)2(OH)Cl(PPh3)] (4) after column chromatography on silica in air. Treatment of 4 with HCl and methyl triflate gave 3 and [Ru(STipp)2(OH)(OTf)(PPh3)] (OTf = triflate, 5), respectively. Reactions of 1 and 2 with p-tolyl azide (p-tolN3) afforded the tetrazene complexes [Ru{N4(p-tol)2}(ER)2(PPh3)] (ER = STipp (6), SeMes (7)), whereas that with tosyl azide (TsN3) gave the imido complexes [Ru(κ2-NTs)(STipp)2(PPh3)] (ER = STipp (8), SeMes (10)). The short Ru-Nimido distances in 8 [1.883(3) Å] and 10 [1.892(2) Å] are indicative of multiple bond character. Treatment of 8 with TsN3 afforded the tetrazene complex [Ru(N4Ts2)(STipp)2(PPh3)] (9), but no cycloaddition was found between 10 and TsN3. Nucleophilic attack of the imido ligand in 10 with methyl triflate yielded the amido complex [Ru(κ2-NMeTs)(SeMes)2(PPh3)](OTf) (11). The crystal structures of 2, 4, 6, and 8-11 have been determined.

Reactions of cerium complexes with transition metal nitrides: synthesis and structure of heterometallic cerium complexes containing bridging catecholate ligands.

In an attempt to synthesize heterometallic cerium nitrido complexes, we studied the reactions of cerium complexes supported by the Kläui tripodal ligand [Co(η5-C5H5){PO(OEt)2}3]- (LOEt-) with transition-metal nitrides. Whereas no reactions were found between Ce-LOEt complexes and [RuVI(LOEt)(N)Cl2] (2), treatment of the Ce(iv) oxo complex [CeIV(LOEt)2(O)(H2O)]·MeCONH2 (1) with 2 resulted in reduction of both the Ce(iv) and Ru(vi) complexes, and formation of a heterometallic Ce(iii)/Ru(iii) complex with a bridging deprotonated acetamide ligand, [(LOEt)2(H2O)CeIII{µ-O,N-MeC(O)NH}RuIII(LOEt)Cl2] (4), along with a minor product, [CeIII(LOEt)2(NO3)]. Ce(iv)-LOEt complexes such as [CeIV(LOEt)2Cl2] (3) can oxidize [ReV(LOEt)(N)(PPh3)Cl] to give the Re(vi) nitride [ReVI(LOEt)(N)(PPh3)Cl]+. Chloride abstraction of 3 by TlPF6 followed by reaction with [PPh4]2[MnV(N)(CN)4] afforded a diamagnetic red solid that is tentatively formulated as a heterometallic Ce(iv)/Mn(v) complex, [Ce(LOEt)2(H2O){Mn(N)(CN)4}] (5). Reactions of 3 with [nBu4N][MVI(N)(cat)2] (cat2- = catecholate(2-)) afforded the Ce(iii)/M(vi) complexes [(LOEt)2CeIII{(µ-cat)2MVI(N)}] [M = Ru (6), Os (7)], in which the Ce(iii) and M(vi) centers are bridged by two oxygen atoms of the two catecholate ligands. Similarly, the catecholate-bridged Ce(iii)/Re(v) complex [(LOEt)2CeIII{(µ-cat)2ReV(O)}] (8) was prepared from 3 and [Me4N][ReV(O)(cat)2]. In CH2Cl2, 8 was air-oxidized to the Ce(iii)/Re(vii) complex [CeIII(LOEt)2(H2O)2][cis-{ReVII(O)2(cat)2}] (9) with a cis-dioxo-Re(vii) counter-anion. The crystal structures of 4, 6, and 9 have been determined.

A Combined Experimental and Theoretical Study of the Versatile Reactivity of an Oxocerium(IV) Complex: Concerted Versus Reductive Addition.

A combined experimental and theoretical investigation on the cerium(IV) oxo complex [(LOEt )2 Ce(=O)(H2 O)]⋅MeC(O)NH2 (1; LOEt - =[Co(η5 -C5 H5 ){P(O)(OEt)2 }3 ]- ) demonstrates that the intermediate spin-state nature of the ground state of the cerium complex is responsible for the versatility of its reactivity towards small molecules such as CO, CO2 , SO2 , and NO. CASSCF calculations together with magnetic susceptibility measurements indicate that the ground state of the cerium complex is of multiconfigurational character and comprised of 74 % of CeIV and 26 % of CeIII . The latter is found to be responsible for its reductive addition behavior towards CO, SO2 , and NO. This is the first report to date on the influence of the multiconfigurational ground state on the reactivity of a metal-oxo complex.

Highly active rare-earth metal catalysts for heteroselective ring-opening polymerization of racemic lactide.

Rare-earth metal complexes usually exhibit high activities in the ring-opening polymerization (ROP) of lactide, yet only a few scandium complexes have shown satisfactory activity. Herein, we report the synthesis of a series of chiral anilido-oxazoline-supported scandium and yttrium complexes that exhibit high activity in the ROP of racemic lactide (rac-LA). Complexes La-f-Ln(CH2SiMe3)2THF (La-f = 2-(2,6-R2PhN)-phenyl-4-(S)-R'-oxazoline; for 1a-f: L = La-f, Ln = Sc; for 2a-d: L = La-d, Ln = Y) were synthesized via the convenient one-pot reaction of Ln(CH2SiMe3)3(THF)2 (Ln = Sc, Y) with the corresponding proligands. The crystal structures of 1a, 1d, 1e, and 1f were isostructural, adopting a distorted trigonal bipyramidal configuration. Sc complexes 1 showed outstanding activity in the ROP of rac-LA with heteroselectivity. TOFs of up to 720 h-1 and 2910 h-1 were obtained in THF at room temperature and toluene at 60 °C, respectively. To our knowledge, these are the highest activities reported for Sc systems. Y complexes 2 showed higher activity and heteroselectivity than the Sc complexes, with TOFs of up to 1176 h-1 in THF at room temperature. Compared with the ortho-substituent on the anilido moiety, the bulky substituent at the chiral center of the oxazoline ring had a greater effect on controlling the heteroselectivity.

Anilido-oxazoline-ligated rare-earth metal complexes: synthesis, characterization and highly cis-1,4-selective polymerization of isoprene.

Anilido-oxazoline-ligated rare-earth metal dialkyl complexes have been synthesized and structurally characterized. The complexes exhibited strong fluorescence emissions and good catalytic performance on isoprene polymerization with high cis-1,4-selectivity. The treatment of anilido-oxazoline precursors ortho-C6H4[NH(2,6-R12C6H3)][C[double bond, length as m-dash]NC(R2,R3)CH2O] (R1 = R2 = R3 = Me (HL1); R1 = iPr, R2 = R3 = Me (HL2); R1 = R2 = iPr, R3 = H (HL3); and R1 = iPr, R2 = R3 = H (HL4)) with an equimolar amount of Ln(CH2SiMe3)3(THF)2 (Ln = Sc, Y) afforded rare-earth metal complexes L1-4-Ln(CH2SiMe3)2(THF)n (L1-Sc (1), n = 1; L2-Sc (2), n = 0; L1-Y (3), n = 1; L2-Y (4), n = 1; L3-Y (5), n = 1; and L4-Y (6), n = 1) in good yields. The complexes are stable in both the solid state and solution. Single crystal X-ray diffraction study showed that complexes 1, 3 and 4 exhibit a distorted trigonal bipyramidal configuration, while complex 2 is pseudo-tetrahedral without coordinated THF. The luminescence properties of complexes 1-4 were investigated and the emission maxima were found in the range of 465-477 nm. DFT and TD-DFT studies were carried out to explore their characteristic electronic structures and gain insight into their optical properties. Upon activation with organic borates, the reported complexes exhibited high activity and cis-1,4-selectivity for isoprene polymerization. The nature of the central metal and substituent groups in oxazoline have an influence on the cis-1,4-selectivity.

Bis(oxazoline)-derived N-heterocyclic carbene ligated rare-earth metal complexes: synthesis, structure, and polymerization performance.

Bis(oxazoline)-derived N-heterocyclic carbene (IBiox) supported rare-earth (Sc, Y, Lu) trialkyl complexes have been synthesized and structurally characterized, and their catalytic activity in the (co)polymerization of α-olefins has been studied. The treatment of Ln(CH2SiMe3)3(THF)2 with one equivalent of freshly prepared IBiox afforded the rare-earth metal complexes (IBiox)Ln(CH2SiMe3)3THFn (Ln = Sc (1), n = 0; Y (2), n = 1; and Lu (3), n = 1) in good yields. Single crystal X-ray diffraction study showed that 1 is pseudo tetrahedral, while 2 and 3 are distorted trigonal bipyramidal with coordinated THF. The Ln-C(carbene) bond distances in 1, 2, and 3 are 2.352, 2.550, and 2.479 Å, respectively. DFT calculations were performed to study the bonding scheme and the structural stability. Complex 1 showed a high activity for 1-hexene polymerization by activation with 2 equivalents of [Ph3C][B(C6F5)4], and the resultant polymers are predominantly vinylene end groups (ca. 95%). Moreover, the catalyst system based on 1 proved to be effective for the copolymerization of 1-hexene with 1,7-octadiene, affording the copolymers with about 20% pendant vinyl groups. The hydrophilicity of the copolymers was improved by modifying the vinyl groups with carboxyls via a thiol-ene reaction.

Tetravalent cerium pseudohalide complexes supported by the Kläui tripodal ligand [Co(η5-C5H5){P(O)(OEt)2}3].

Cerium(iv) pseudohalide complexes supported by the Kläui tripodal ligand [Co(η5-C5H5){P(O)(OEt)2}3]- (LOEt-) have been synthesized and structurally characterized. The treatment of [CeIV(LOEt)2Cl2] (1) with 2 equivalents of [AgX] in acetonitrile afforded [CeIV(LOEt)2X2] [X- = NCS- (2), N3- (3), F- (4)]. The reaction of 1 with [AgCN] in dichloromethane at -40 °C led to formation of a bimetallic CeIV/AgI cyanide complex that decomposed in solution at room temperature. In the presence of BPh3, 1 reacted with [AgCN] to yield the cyanoborate complex [CeIV(LOEt)2(NCBPh3)2] (6) that is stable in solution. The chlorination of [CeIII(LOEt)2(NO3)] with PhICl2 afforded [CeIV(LOEt)2(NO3)Cl] (7) that reacted with [AgCN] to yield the heterometallic CeIV/AgI cyanide complex [{Ce(LOEt)2(NO3)}2{µ-Ag(CN)2}][AgCl2] (8). The reaction of [CeIV(LOEt)Cl3] with [AgN3] afforded the tetranuclear CeIV oxo azido cluster [Ce4(LOEt)4(µ4-O)(µ2-O)2(µ2-N3)6] (9). The structures of complexes 2, 3, 6 and 9 have been established by X-ray crystallography.