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Biomedical subjects

K M Smith

Publications and source records attributed to K M Smith.

At least 19 recordsLinked to original sources
PubMed2006

Development of GnRH cells: Setting the stage for puberty.

Cells containing gonadotropin-releasing hormone (GnRH) are essential not only for reproduction but also for neuromodulatory functions in the adult animal. A variety of studies have hinted at multiple origins for GnRH-containing cells in the developing embryo. We have shown, using zebrafish as a model system, that GnRH cells originate from precursors lying outside the olfactory placode: the region of the anterior pituitary gives rise to hypothalamic GnRH cells and the cranial neural crest gives rise to the GnRH cells of the terminal nerve and midbrain. Cells of both the forming anterior pituitary and cranial neural crest are closely apposed to the precursors of the olfactory epithelium during early development. Disruption of kallmann gene function results in loss of the hypothalamic but not the terminal nerve GnRH cells during early development. The GnRH proteins are expressed early in development and this expression is mirrored by the onset of GnRH receptor (GnRH-R) expression during early development. Thus the signaling of the GnRH neuronal circuitry is set up early in development laying the foundation for the GnRH network that is activated at puberty leading to reproductive function in the mature animal.

Animals↗
PubMed2006

Passenger seating position and the risk of passenger death in traffic crashes: a matched cohort study.

OBJECTIVE: To estimate the association of passenger seating position with the risk of death for passengers in traffic crashes. DESIGN, SETTING, PARTICIPANTS: Matched cohort analysis of data from the National Highway Traffic Safety Administration Fatality Analysis Reporting System regarding 56 644 passengers in 23 308 passenger cars, light trucks, vans, and sport utility vehicles that crashed during 1990-2001. MAIN OUTCOME MEASURE: The adjusted risk ratio (aRR) for death of a rear seat passenger compared with a front seat passenger within 30 days of a crash. RESULTS: The aRR for all passengers in the rear seat in a crash was 0.79 (95% CI 0.77 to 0.82). This estimate varied by age, restraint use, and the presence of a front passenger airbag (p<0.001). For restrained passengers in cars with a front passenger airbag, the aRR was 0.62 (95% CI 0.48 to 0.81) for children 0-12 years, 0.96 (95% CI 0.88 to 1.06) for passengers 13-29 years, 1.03 (95% CI 0.93 to 1.15) for passengers 30-59 years, and 1.06 (95% CI 0.90 to 1.26) for passengers 60 years or older. The rear seat was associated with more protection in cars without front airbags and more protection for unrestrained passengers compared with restrained passengers. CONCLUSIONS: Previous studies have reported that the rear seat was safer for persons of all ages; thus seating a young child in the rear has often meant that older children and adults had to assume an increased risk of death by sitting in the front. These results suggest that when front passenger airbags are present and passengers are restrained, putting adults in front and children in back enhances child safety without sacrificing adult safety.

Accidents, Traffic↗
PubMed2006

Changes in traffic crash mortality rates attributed to use of alcohol, or lack of a seat belt, air bag, motorcycle helmet, or bicycle helmet, United States, 1982-2001.

OBJECTIVE: To estimate the contributions of five risk factors to changes in US traffic crash mortality: (1) alcohol use by drivers and pedestrians, (2) not wearing a seat belt, (3) lack of an air bag, (4) not wearing a motorcycle helmet, and (5) not wearing a bicycle helmet. DESIGN: Longitudinal study of deaths; attributable deaths were estimated using data from other studies. SETTING: US traffic crashes in 1982-2001. SUBJECTS: People who died in a crash. MAIN OUTCOME MEASURES: Counts of deaths attributed to each risk factor, change in rates of deaths, and counts of lives saved by changes in risk factor prevalence. RESULTS: There were 858 741 traffic deaths during the 20 year period. Estimated deaths attributed to each factor were: (1) alcohol use, 366 606; (2) not wearing a seat belt, 259 239; (3) lack of an air bag, 31 377; (4) no motorcycle helmet, 12 095; (5) no bicycle helmet, 10 552. Over the 20 years, mortality rates attributed to each risk factor declined: alcohol by 53%; not wearing a seat belt by 49%; lack of an air bag by 17%; no motorcycle helmet by 74%; no bicycle helmet by 39%. There were 153 168 lives saved by decreased drinking and driving, 129 297 by increased use of seat belts, 4305 by increased air bag prevalence, 6475 by increased use of motorcycle helmets, and 239 by increased use of bicycle helmets. CONCLUSIONS: Decreased alcohol use and increased use of seat belts were associated with substantial reductions in crash mortality from 1982 through 2001. Increased presence of air bags, motorcycle helmets, and bicycle helmets were associated with smaller reductions.

Accidents, Traffic↗
PubMed2005

Activation of 12-lipoxygenase in proinflammatory cytokine-mediated beta cell toxicity.

AIMS/HYPOTHESIS: Beta cell inflammation and cytokine-induced toxicity are central to autoimmune diabetes development. Lipid mediators generated upon lipoxygenase (LO) activation can participate in inflammatory pathways. 12LO-deficient mice are resistant to streptozotocin-induced diabetes. This study sought to characterise the cellular processes involving 12LO-activation lipid inflammatory mediator production in cytokine-treated pancreatic beta cells. METHODS: Islets and beta cell lines were treated with a combination of IL-1beta, IFN-gamma and TNF-alpha, or the 12LO product 12(S)-hydroxyeicosatetraenoic acid (HETE). Insulin secretion was measured using an enzyme immunoassay, and cell viability was evaluated using an in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay. 12LO activity was evaluated and 12LO protein levels were determined using immunoblotting with a selective leucocyte type 12LO antibody. Cellular localisation of 12LO was evaluated using immunocytochemistry. RESULTS: Basal expression of leucocyte type 12LO protein was found in human and mouse islets and in several rodent beta cell lines. In mouse beta-TC3 cells, and in human islets, cytokines induced release of 12-HETE within 30 min. Cytokine addition also induced a rapid translocation of 12LO protein from the cytosol to the nucleus of beta-TC3 cells as shown by subcellular fractionation and immunostaining. Cytokine-induced cell death and inhibition of insulin secretion were partially reversed by baicalein, a 12LO inhibitor. 12(S)-HETE inhibited beta-TC3 cell insulin release in a time- and concentration-dependent manner. Incubating beta-TC3 cells with 100 nmol/l of 12(S)-HETE resulted in a 57% reduction in basal insulin release (6 h), and a 17% increase in cell death (18 h) as compared with untreated cells. 12(S)-HETE activated the stress-activated protein kinase c-Jun N-terminal kinase and p38 within 15 min, as judged by increased kinase protein phosphorylation. CONCLUSIONS/INTERPRETATION: The data suggest that inflammatory cytokines rapidly activate 12LO and show for the first time that cytokines induce 12LO translocation. The effects of 12-HETE on insulin secretion, cytotoxicity and kinase activation were similar to the effects seen with cytokines. The results provide mechanistic information of cytokine-induced toxic effects on pancreatic beta cells and support the hypothesis that blocking 12LO activation could provide a new therapeutic way to protect pancreatic beta cells from autoimmune injury.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2004

Tension free vaginal tape: is the intra-operative cough test necessary?

The tension-free vaginal tape (TVT) procedure is recognised as an effective treatment for genuine stress incontinence. It was first described using local anaesthesia, with an intra-operative cough test helping to correctly position the tape. Many patients prefer general anaesthesia and often, patients with genuine stress incontinence do not leak when supine. This aim of this study was to compare the outcome in TVTs performed under general anaesthesia with those performed under spinal anaesthesia. Retrospective analysis of 105 patients, all of whom had urodynamically proven genuine stress incontinence and underwent TVT procedure, was performed: 52 under spinal anaesthesia and 53 under general anaesthesia. The primary and secondary outcome measures were the success or failure of the procedure and the complication rate, respectively. There was no significant difference in outcome or complication rate between the two groups. The type of anaesthetic used does not influence the outcome and we question the necessity of an intra-operative cough test.

Cough↗
PubMed2004

Synthesis of novel carboranylchlorins with dual application in boron neutron capture therapy (BNCT) and photodynamic therapy (PDT).

Total synthesis of carboranylchlorins 3 and 4, from readily available starting materials, are described and the molecular structures of two key intermediates are presented. Chlorins 3 and 4 show similar spectroscopic behavior but differ considerably in their solubility properties; whereas closo-carboranylchlorin 3 is completely insoluble in water, its nido derivative 4 has good water-solubility. Carboranylchlorin 3 absorbs in the red region of the optical spectrum (at lambda(max)=642 nm) six times more strongly than porphyrin 1, and displays a fluorescence emission band at lambda(max)=651 nm, upon excitation at 642 nm. The water-soluble carboranylchlorin 4 also displays intense absorption and emission bands at lambda(max)=642 and 651 nm, respectively, in ethanol solution. It is concluded that carboranylchlorins 3 and 4 have higher promise for the dual application in PDT and BNCT than do comparable porphyrins.

Boron Neutron Capture Therapy↗
PubMed2004

Inflammation blockade improves pancreatic islet function.

Pancreatic islet transplantation can replace insulin-secreting beta cells in patients with diabetes mellitus. However, current methodology for isolating islets from a pancreas only retrieves a portion of the total islets. Within these limited number of islets, nearly 50% of beta cells lose biological function before transplantation. Protecting and improving beta-cell viability and function was the goal of this study. Previously we observed that an anti-inflammatory compound, lisofylline (LSF), protects beta cells from cytotoxicity during diabetes development. In this study, we demonstrated that human islets treated in vitro with LSF retained beta-cell glucose responsiveness and insulin secretion in the presence of multiple proinflammatory cytokines. In addition, LSF treatment in vitro enhanced basal insulin production in beta cells, suggesting that LSF can directly improve beta-cell function. LSF reduced beta-cell apoptosis induced by proinflammatory cytokines by 50%. Importantly, 30% fewer LSF-treated islets were sufficient to achieve insulin independence in a murine islet transplantation model. These results demonstrate the ability of LSF-like compounds to protect and enhance beta-cell function, suggesting the potential of using LSF or its analogs in islet transplantation.

Animals↗
PubMed2004

Impact of donor immune cells in pancreatic islet transplantation.

Autoimmune-mediated cytotoxicity may cause pancreatic islet transplant failure, leading to recurrent diabetes. Protection of islet grafts depends on immunosuppressive control, which may also prevent autoimmune recurrence of diabetes. In this study, we compared the survival of syngeneic islet transplants using different strains of donor mice. We observed extended functional survival in the islet grafts from donors lacking the genetic background and potential of autoimmunity. Without immunosuppression, the islet grafts of NOR and immune-deficient NOD. Scid donors functioned up to 3 weeks in syngeneic islet transplants compared to 3-day survivals with the grafts from NOD donors. T-cell proliferation and activation markers, CD44 and CD69, were upregulated in NOD donors, suggesting that T-cell activation had occurred prior to pancreas procurement. Systemic delivery of a recombinant adenoassociated viral vector (AAV) encoding the viral (vIL-10) IL-10 gene (AAV vIL-10) in NOD recipients protected syngeneic islets from autoimmune destruction. Alternatively, pretreatment of NOD donor mice with AAV vIL-10 prolonged islet graft survival in untreated NOD recipients. Both studies indicate the effectiveness of vIL-10 gene therapy in autoimmune regulation. These results suggest that a donor factor may exist in autoimmune-prone donors. Therefore, autoimmune recurrence of diabetes may result from donor immune cells transferred during islet transplantation. The AAV vIL-10 gene therapy suppressed previously activated donor T cells and protected the grafted islets from autoimmune-mediated destruction.

Animals↗
PubMed2001

1H and 13C NMR investigation of the influence of nonligated residue contacts on the heme electronic structure in cyanometmyoglobin complexes reconstituted with centro- and pseudocentrosymmetric hemins.

The 1H and 13C chemical shifts for the heme methyls of low-spin, ferric sperm whale cyanometmyoglobin reconstituted with a variety of centrosymmetric and pseudocentrosymmetric hemins have been recorded and analyzed to shed light on the nature of heme-protein contacts, other than that of the axial His, that modulate the rhombic perturbation to the heme's in-plane electronic asymmetry. The very similar 1H dipolar shifts for heme pocket residues in all complexes yield essentially the same magnetic axes as in wild type, and the resultant dipolar shifts allow the direct determination of the heme methyl proton and 13C contact shifts in all complexes. It is demonstrated that, even when the magnetic axes and anisotropies are known, the intrinsic uncertainties in the orientational parameters lead to a sufficiently large uncertainty in dipolar shift that the methyl proton contact shifts are inherently significantly less reliable indicators of the unpaired electron spin distribution than the methyl 13C contact shifts. The pattern of the noninversion symmetry in 13C contact shifts in the centro- or pseudocentrosymmetric hemes is shown to correlate with the positions of aromatic rings of Phe43(CD1) and His97(FG3) parallel to, and in contact with, the heme. These results indicate that such pi-pi interactions significantly perturb the in-plane asymmetry of the heme pi spin distribution and cannot be ignored in a quantitative interpretation of the heme methyl 13C contact shifts in terms of the axial His orientation in b-type hemoproteins.

Animals↗
PubMed2001

Outcomes and costs of coronary artery bypass grafting: comparison between octogenarians and septuagenarians at a tertiary care centre.

BACKGROUND: Decision-making related to coronary artery bypass grafting (CABG) in elderly patients is hampered by inadequate outcome data. We compared the clinical outcomes of octogenarians with those of septuagenarians who underwent CABG. Our secondary objective was to compare the costs associated with CABG in these groups. METHODS: We conducted a retrospective database review of patients 70 years of age and older who had undergone CABG at a regional cardiac surgical centre in Hamilton, Ont., between July 1, 1997, and Apr. 30, 2000. A total of 1034 patients were divided into 3 age groups: young septuagenarians (aged 70-74 years), old septuagenarians (aged 75-79) and those 80 and older. Costs were determined in a subset of 773 patients with the use of a case-costing system for cardiac surgery developed at our institution. RESULTS: The 3 groups were similar with respect to sex distribution and preoperative risk factors. Urgency scores at referral differed significantly between the groups, with the young septuagenarians demonstrating the lowest risk (mean score [and standard deviation] 4.48 [1.3] in that group, 4.28 [1.4] in the old septuagenarian group and 4.11 [1.2] in the octogenarian group). The rates of all complications combined were similar between the 3 groups (27.1%, 28.1% and 29.6% in the young and old septuagenarian groups and the octogenarian group respectively). There were no significant differences between the 3 groups in the mean number of grafts per patient (3.0, 3.1 and 3.0 respectively), the rate of postoperative death (3.3%, 5.7% and 4.2%), the mean length of stay (11.7, 13.4 and 12.6 days) or the incidence of postoperative myocardial infarction (4.5%, 3.4% and 4.2%). The total cost of CABG per patient did not differ significantly between the 3 groups. INTERPRETATION: Given that patients who are accepted for CABG represent a selected population, our findings suggest that, with careful triage, CABG in octogenarians is as safe as, and no more costly than, CABG in septuagenarians.

Age Factors↗
PubMed2001

Preparation, characterization, and luminescence properties of gallium-metal face-to-face diporphyrins (M = H(2), GaL, Ru(CO)(OH), Co).

The preparation and characterization of a new series of mixed metal cofacial anthracene-bridged diporphyrins (DPA) containing a GaL fragment (L = OMe, OH) and another metallic center (M = GaL, Ru(CO)(OH), Co, and H(2) (i.e. free base)) are reported. The luminescence properties at 298 and 77 K, in degassed EtOH solution, are also reported, and are characterized by a weak pipi fluorescence (2 < tau(F) < 7 ns) arising from the low energy Q-bands (S(1)-->S(0)). In the mixed diporphyrin systems, a strong pipi fluorescence is detected from the free base, while the transition metalloporphyrins of Co(II) and Ru(II) do not emit. The homobimetallic di[Ga(OMe)] species exhibits an unprecedented double (pi)(pi) fluorescence arising from the two lowest energy absorption Q-bands. On the basis of a comparison with photophysical data on GaL monoporphyrins, the weak fluorescence and absence of phosphorescence for most cases indicate efficient intramolecular quenching. To define structural features, the X-ray structures of (DPA)[Ga(OMe)](2) (2), (DPA)[Ga-(OH)-Ru(CO)] (5a), and (DPA)[Ga(OMe)-Ru(MeOH)(CO)] (5b) have been obtained. The structures of 5a and 5b demonstrate an interesting aspect of the structural chemistry of these ligands related to the internal methoxide and methanolic ligands in 5b (resulting in a large interplanar separation and center-to-center distance) and the internal metal-bridging hydroxyl ligand in 5a (resulting in a small interplanar separation and center-to-center distance). These data support previously reported discussions on the ability of the DPA and the DPB analogue (diporphyrinylbiphenylenyl) ligands to open and close their "bite" around the binding pocket between the porphyrin macrocycles.

Journal Article↗
PubMed2001

Molecular structures and magnetic resonance spectroscopic investigations of highly distorted six-coordinate low-spin iron(III) porphyrinate complexes.

Three bis-axially ligated complexes of iron(III) octaethyltetraphenylporphyrin, (OETPP)Fe(III), have been prepared, which are low-spin complexes, each with two axial nitrogen-donor ligands (N-methylimidazole (N-MeIm), 4-(dimethylamino)pyridine (4-NMe(2)Py), and 2-methylimidazole (2-MeImH)). The crystal and molecular structure of the bis-(2-MeImH) complex shows the macrocycle to be in a saddled conformation, with the ligands in perpendicular planes aligned at 14 degrees to the porphyrin nitrogens so as to relieve the steric interaction between the 2-methyl groups and the porphyrin. The Fe-N(por) bond lengths are typical of nonplanar six-coordinate low-spin Fe(III) complexes, while the axial Fe-N(ax) bond lengths are substantially longer than those of [(TPP)Fe(2-MeImH)(2)](+) (2.09(2) A as compared to 2.015(4) and 2.010(4) A). The crystal and molecular structure of the bis-(4-NMe(2)Py) complex also shows the macrocycle to be in a mainly saddled conformation, but with a significant ruffled component. As a result, the average Fe-N(por) bonds are significantly shorter (1.951 A as compared to 1.974 A) than those of the bis-(2-MeImH) complex. One ligand is aligned at 9 degrees to two trans porphyrin nitrogens, while the other is at 79 degrees to the same porphyrin nitrogens, producing a dihedral angle of 70 degrees between the ligand planes. The EPR spectrum of this complex, like that of the bis-(2-MeImH) complex, is of the "large g(max)" type, with g(max) = 3.29 and 3.26, respectively. However, in frozen CD(2)Cl(2), [(OETPP)Fe(N-MeIm)(2)](+) exhibits both "large g(max)" and normal rhombic signals, suggesting the presence of both "perpendicular" and "parallel" ligand orientations. The 1- and 2D (1)H NMR spectra of each of these complexes, as well as the chloroiron(III) starting material, were investigated as a function of temperature. The COSY and NOESY/EXSY spectra of the chloride complex are consistent with the expected J-coupling and saddle inversion dynamics, respectively. Complete spectral assignments for the bis-(N-MeIm) and -(4-NMe(2)Py) complexes have been made using 2D (1)H NMR techniques. In each case, the number of resonances due to methylene (two) and phenyl protons (one each) is consistent with D(2)(d)() symmetry, and therefore an effective perpendicular orientation of the axial ligands on the time scale of the NMR experiments. The temperature dependences of the (1)H resonances of these complexes show significant deviations from Curie behavior, and also evidence of extensive ligand exchange and rotation. Spectral assignment of the eight methylene resonances of the bis-(2-MeImH) complex to the four ethyl groups was possible through the use of 2D (1)H NMR techniques. The complex is fluxional, even at -90 degrees C, and ROESY data suggest that the predominant process is saddle inversion accompanied by simultaneous rotation of the axial ligands. Saddle inversion becomes slow on the 2D NMR time scale as the temperature is lowered in the ligand order of N-MeIm > 4-NMe(2)Py > 2-MeImH, probably due mainly to progressive destabilization of the ground state rather than progressive stabilization of the transition state of the increasingly "hindered" bis-ligand complexes.

Electron Spin Resonance Spectroscopy↗
PubMed2001

Effect of meso-substituents on the osmium tetraoxide reaction and pinacol-pinacolone rearrangement of the corresponding vic-dihydroxyporphyrins.

To investigate the effects of electron-donating and electron-withdrawing substituents upon the reaction of porphyrins with osmium tetraoxide, and the pinacol-pinacolone rearrangement of the resulting diols, a series of meso-substituted porphyrins were prepared by total synthesis. Porphyrins with electron-donating substitutents at the meso-positions gave vic-dihydroxychlorins in which the adjacent pyrrole subunit was predominantly oxidized. No such selectivity was observed in a porphyrin containing a methoxycarbonyl as the electron-withdrawing group, whereas a formyl substituent again resulted in oxidation at the pyrrole unit adjacent to the meso-substituent. Under pinacol-pinacolone conditions, vic-dihydroxy chlorins containing 4-methoxyphenyl or 3,5-dimethoxyphenyl groups at the meso-position showed preferential migration of the ethyl group over the methyl group to give 8-ketochlorins, whereas the diol with an n-heptyl substituent under similar reaction conditions gave both 7- and 8-ketochlorins. In contrast, the diol containing a meso-formyl substituent produced the corresponding 7-ketochlorin exclusively. These results indicate that it is not possible to predict the reactivity of meso-substituted porphyrins in the osmium tetraoxide reaction nor the general substituent migratory aptitudes in the pinacol-pinacolone rearrangement based on simple electronic arguments, most likely because many parameters (e.g., meso-beta-pyrrolic steric crowding and long-range electronic effects) ultimately determine the reactivity. The structural assignments of the porphyrin diols and the keto-analogues were confirmed by extensive (1)H NMR studies; some of the dihydroxychlorins and ketochlorins were found to display unusual features in their (1)H NMR spectra.

Alkylation↗
PubMed2001

Activation of c-Abl kinase activity and transformation by a chemical inducer of dimerization.

c-Abl is a non-receptor tyrosine kinase that is activated in human leukemias by the fusion of Bcr or Tel sequences to the Abl NH(2) terminus. Although Bcr and Tel have little in common, both contain oligomerization domains. To determine whether oligomerization alone is sufficient to activate c-Abl, we have generated and characterized an Abl protein that can be activated selectively with the chemical inducer of dimerization, AP1510. Mutant Abl proteins with one (c4F1) or two (c4F2) copies of the AP1510 binding motif (FKBP) transformed NIH 3T3 cells in a ligand-dependent manner with the c4F2 protein 60-fold more potent than c4F1. Both chimeric proteins exhibited ligand-dependent dimerization in vivo, suggesting that the increased transformation efficiency of the c4F2 mutant reflects more effective dimerization rather than formation of higher order oligomers. In the absence of ligand, c4F2-expresssing fibroblasts morphologically reverted and arrested in G(1). In Ba/F3 cells, the c4F2 chimera exhibited ligand-dependent kinase activation, transformation to interleukin 3-independent growth, and relocalization of the fusion protein from nucleus to cytoplasm. These results demonstrate that dimerization alone is sufficient to activate the Abl kinase and provide a method to regulate conditionally c-Abl activity that will be useful for studying the normal physiological role of c-Abl and the mechanism of transformation and leukemogenesis.

3T3 Cells↗
PubMed2001

A computational study of ethylene C-H bond activation by.

It has previously been demonstrated that both [(C5Me5)Ir(PMe3)(CH=CH2)H] and [(C5Me5)Ir(PMe3)(H2C=CH2)] are formed when [(C5Me5)Ir(PMe3)] is thermolytically generated in the presence of ethylene. At higher temperatures, the vinyl hydride is converted to the eta2-ethylene adduct. Density functional theory has now been used to investigate this reaction, using the B3LYP functional, two types of basis sets (LanL2DZ and TZV*), and two models of the [(C5R5)Ir(PR3)] species (R=H and CH3). The study consists of full optimizations of local minima, first-order saddle points, and minimum energy crossing points (MECP). The experimental results are best accounted for by considering both singlet and triplet spin surfaces. The relative energies of singlet [(C5R5)Ir(PR3)(CH3)H], [(C5R5)Ir(PR3)(CH=CH2)H], and [(C5R5)Ir(PR3)(H2C=CH2)] are in good agreement with experiment, as is the calculated barrier for the conversion from the vinyl hydride to the eta2-alkene complex. However, the singlet surface alone fails to explain the experimentally observed product ratio, or the intermediate inferred from experimental isotope effect studies. Locating the MECP between singlet and triplet surfaces indicates that the thermolysis of the singlet alkyl hydride precursor directly forms triplet [(C5R5)Ir(PR3)]. The weak vanderWaals adduct of triplet [(C5R5)Ir(PR3)] and ethylene is proposed to be the key intermediate in the overall reaction. The interchanging of the available ethylene C-H bonds in this triplet sigma complex accounts for the observed kinetic isotope effects, and partitioning between alkene pi-complexation and C-H bond activation may also occur from this common intermediate. The possible role of steric factors and molecular dynamics are also discussed.

Journal Article↗