Elucidation of the Pyridine Ring-Opening Mechanism of 2,2'-Bipyridine or 1,10-Phenanthroline Ligands at Re(I) Carbonyl Complexes.

The cleavage of the C-N bonds of aromatic heterocycles, such as pyridines or quinolines, is a crucial step in the hydrodenitrogenation (HDN) industrial processes of fuels in order to minimize the emission of nitrogen oxides into the atmosphere. Due to the harsh conditions under which these reactions take place (high temperature and H2 pressure), the mechanism by which they occur is only partially understood, and any study at the molecular level that reveals new mechanistic possibilities in this area is of great interest. Herein, we unravel the pyridine ring-opening mechanism of 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen) ligands coordinated to the cis-{Re(CO)2(N-RIm)(PMe3)} (N-RIm= N-alkylimidazole) fragment under mild conditions. Computational calculations show that deprotonation of the pyridine ring, once dearomatized, is crucial to induce ring contraction, triggering extrusion of the nitrogen atom from the ring and cleavage of the C-N bond. It is noteworthy that different products (regioisomers) are obtained depending on whether the ligand used is bipy or phen due to the additional rigidity and stability conferred by the central ring of the phen ligand, an issue also addressed and clarified computationally. Strong support for the proposed mechanism is provided by the characterization and isolation, including three single-crystal X-ray diffraction structures, of several of the proposed reaction intermediates.

Dynamical effects on the O(3P) + D2 reaction and its impact on the Λ-doublet population.

The O(3P) + D2 → OD(2Π) + D reaction presents the peculiarity of taking place on two different potential energy surfaces (PESs) of different symmetry, 3A' and 3A'', which become degenerate for collinear configurations where the saddle-point of the reaction is located. The degeneracy is broken for non-collinear approaches with the energy on the 3A' PES rising more abruptly with the bending angle, making the frequency of this mode higher on the 3A' state. Consequently, the 3A' PES should be less reactive than the 3A'' one. Nevertheless, quantum scattering calculations show that the cross section is higher on the 3A' PES for energies close to the classical reaction threshold and rotationless reactant. It is found that the differences between the reactivity on the two PESs are greater for low values of total angular momentum, where the centrifugal barrier is lower and contribute to the higher population of the Π(A') Λ-doublet states of OD at low collision energies. At high collision energies, the Π(A') Λ-doublet state is also preferentially populated. Analysis of the differential cross sections reveals that the preponderance for the Π(A') Λ-doublet at low energies comes from backward scattering, originating from the reaction on the 3A' PES, while at high energies, it proceeds from a different mechanism that leads to sideways scattering on the 3A'' PES and that populates the Π(A') manifold.

Computational Design of Rhenium(I) Carbonyl Complexes for Anticancer Photodynamic Therapy.

New Re(I) carbonyl complexes are proposed as candidates for photodynamic therapy after investigating the effects of the pyridocarbazole-type ligand conjugation, addition of substituents to this ligand, and replacement of one CO by phosphines in [Re(pyridocarbazole)(CO)3(pyridine)] complexes by means of the density functional theory (DFT) and time-dependent DFT. We have found, first, that increasing the conjugation in the bidentate ligand reduces the highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy gap of the complex, so its absorption wavelength red-shifts. When the enlargement of this ligand is carried out by merging the electron-withdrawing 1H-pyrrole-2,5-dione heterocycle, it enhances even more the stabilization of the LUMO due to its electron-acceptor character. Second, the analysis of the shape and composition of the orbitals involved in the band of interest indicates which substituents of the bidentate ligand and which positions are optimal for reducing the HOMO-LUMO energy gap. The introduction of electron-withdrawing substituents into the pyridine ring of the pyridocarbazole ligand mainly stabilizes the LUMO, whereas the HOMO energy increases primarily when electron-donating substituents are introduced into its indole moiety. Each type of substituents results in a bathochromic shift of the lowest-lying absorption band, which is even larger if they are combined in the same complex. Finally, the removal of the π-backbonding interaction between Re and the CO trans to the monodentate pyridine when it is replaced by phosphines PMe3, 1,4-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA), and 1,4,7-triaza-9-phosphatricyclo[5.3.2.1]tridecane (CAP) causes another extra bathochromic shift due to the destabilization of the HOMO, which is low with DAPTA, moderate with PMe3, but especially large with CAP. Through the combination of the PMe3 or CAP ligands with adequate electron-withdrawing and/or electron-donating substituents at the pyridocarbazole ligand, we have found several complexes with significant absorption at the therapeutic window. In addition, according to our results on the singlet-triplet energy gap, all of them should be able to produce cytotoxic singlet oxygen.

Loss of p16 expression is a risk factor for recurrence in sinonasal inverted papilloma.

BACKGROUND: The purpose of this study was to evaluate p16, p53, EGFR, pEGFR protein expression and HPV infection as possible markers of tumor progression in a series of sinonasal inverted papilloma (SNIP) and sinonasal squamous cell carcinoma (SNSCC). METHODS: A series of 49 SNIP, 11 SNSCC associated with SNIP (SNIP-SNSCC) and 52 SNSCC not associated with SNIP were analyzed for p16, p53, EGFR, and phosphorylated EGFR (pEGFR) expression by immunohistochemistry. Human papillomavirus (HPV) infection status was evaluated by DNA-PCR. Results were correlated to clinical and follow-up data. RESULTS: Reduced or loss of p16 expression was observed in 18% SNIP, 64% SNIP-SNSCC and 87% of SNSCC. Reduced or loss p16 staining in SNIP correlated with shorter recurrent SNIP-free follow-up. In contrast, p16 expression was not predictive of recurrent SNSCC in cases with SNIP-SNSCC and SNSCC. P53, EGFR, and pEGFR expression did not differ between the tumor groups, nor were they related to recurrent SNIP-free follow-up or recurrent SNSCC. Oncogenic HPV types 16 and 18 were detected in 5% of SNIP and 18% of SNIP-SNSCC, but not in SNSCC. There was no correlation between HPV infection and >70% p16 immunostaining. CONCLUSIONS: HPV infection appears to play a minor role in SNIP and SNSCC and p16 immunostaining does not appear a valid surrogate marker for HPV. However, reduced or loss p16 expression may have prognostic value as a risk marker for recurrent SNIP.

Epidemiology of Bone Fractures in the Hand in Adult Population Using the ICD-10 Classification.

PURPOSE OF THE STUDY The purpose of this study was to conduct an epidemiological study of hand fractures in adult population. MATERIAL AND METHODS A retrospective observational study in a population of 470,000 habitants was performed. Over the course of three years, all patients over 16 years of age who were diagnosed with fracture or fracture-dislocation at the level of a carpal bone, metacarpal and/or phalange were included. These fractures were classified according to the International Classification of Diseases 10th edition (ICD-10). Incidence rates, along with gender and age distribution were also studied. RESULTS 1,267 patients with a total of 1,341 hand fractures were included. They represented 29.7% of all upper limb fractures and 7.6% of all traumatological emergencies involving a bone fracture during that period. The most frequent ICD-10 group was S62.3, with the fifth metacarpal as the most often affected bone (39.7%). The most frequent location at the level of the phalanges (S62.5) was the proximal third of the proximal phalanx of the fifth radius. The global incidence rate was 99 fractures per 100,000 persons/year. No seasonal variation was observed. Only 10.2% of hand fractures received surgical treatment. DISCUSSION Several epidemiological studies have been published on fractures in the hand, but none have used the ICD-10 classification. Although the distribution of our stratified sample by age and gender was similar to those previously published, the incidence rate in our study was much lower. We may possibly extrapolate our results to the rest of the Spanish population and even to the rest of the population of southern Europe, given the scarcity of epidemiological studies on this matter in these geographical areas. CONCLUSIONS The ICD-10 classification is useful for the description and classification of hand fractures. The most often affected group is that including metacarpals of the long fingers (S62.3), being the distal level of the fifth metacarpal in young male patients the most frequent one. Most fractures are treated conservatively and in case of surgical treatment, the preferred surgical techniques include K-wire fixation, interfragmentary compression screws and plate osteosynthesis. Key words: epidemiology, incidence, fracture, fracture dislocation, carpal bones, metacarpals, finger phalanges.

Unveiling shape resonances in H + HF collisions at cold energies.

Scattering resonances are pure quantum effects that appear whenever the collision energy matches the energy of a quasi-bound state of the intermolecular complex. Here we show that rotational quenching of HF(j = 1, 2) with H is strongly influenced by the presence of two resonance peaks, leading to up to a two-fold increase in the thermal rate coefficients at the low temperatures characteristic of the interstellar medium. Our results show that each resonance peak is formed by a cluster of shape resonances, each of them characterized by the same value of the orbital angular momentum but different values of the total angular momentum. The relative intensity of these resonances depends on the relative geometry of the incoming reactants, and our results predict that by changing the alignment of the HF rotational angular momentum it is possible to decompose the resonance peaks, disentangling the underlying resonance pattern and the contribution of different total angular momenta to the resonance.

Reclaiming the Autopsy as the Practice of Medicine: A Pathway to Remediation of the Forensic Pathology Workforce Shortage?

The historically constricted forensic pathology workforce pipeline is facing an existential crisis. Pathology residents are exposed to forensic pathology through the American Council of Graduate Medical Education autopsy requirement. In 1950, autopsies were conducted in one half of the patients dying in American hospitals and 90% in teaching hospitals, but they have dwindled to fewer than 5%. Elimination of funding for autopsies is a major contributor to the lack of support for autopsies in departments of pathology. Funding may require reclaiming the autopsy as the practice of medicine. Funding of autopsies would rekindle interest in hospital autopsies and strengthen the forensic pathology workforce pipeline.

EGFR mutation and HPV infection in sinonasal inverted papilloma and squamous cell carcinoma.

BACKGROUND: To evaluate the involvement of EGFR signalling and HPV infection in a cohort of inverted sinonasal papilloma (ISP) and sinonasal squamous cell carcinoma (SNSCC) and their value for prognosis and clinical treatment. METHODS: We analysed 55 ISP, 14 SNSCC associated with ISP (SNSCC-isp) and and 60 SNSCC not associated with ISP (SNSCC-novo) for EGFR gene mutation and copy number gain, protein expression of EGFR and phosporylated EGFR (pEGFR), and HPV-infection and KRAS mutation. Findings were correlated to clinico-pathological and follow-up data. RESULTS: We found EGFR exon 20 mutations in 38% (7/18) ISP, in 50% (6/12) SNSCC-isp and in 5% (1/19) SNSCC-novo. EGFR was expressed in 92% of ISP, while pEGFR was observed in 54% (21/39). SNSCC-isp and SNSCC-novo demonstrated comparable expression of EGFR (57% and 33%) and of pEGFR (44% and 38%). We observed an inverse relation between EGFR exon 20 mutation and pEGFR expression. Four of 39 (10%) ISP carried HPV-16. Oncogenic HPV was detected in 3/12 (25%) SNSSC-isp and in 1/8 (13%) SNSCC-novo. KRAS mutations were not detected in any of the samples. HPV infection was inversely correlated with pEGFR expression but not with EGFR mutation. ISP with EGFR activation by mutation or by phosphorylation had longer ISP-free survival, however, neither EGFR exon 20 mutation, pEGFR expression nor HPV infection demonstrated prognostic value in SNSCC. CONCLUSIONS: EGFR exon 20 mutation is frequent in ISP and SNSCC-isp, while activation of EGFR through phosphorylation also plays an important role. Our data indicate that a large proportion of SNSCC patients could benefit from therapy with modern EGFR inhibitors.

Influence of the Nucleophilic Ligand on the Reactivity of Carbonyl Rhenium(I) Complexes towards Methyl Propiolate: A Computational Chemistry Perspective.

A comparative theoretical study on the reactivity of the complexes [ReY(CO)3(bipy)] (Y = NH2, NHMe, NHpTol, OH, OMe, OPh, PH2, PHMe, PMe2, PHPh, PPh2, PMePh, SH, SMe, SPh; bipy = 2,2'-bipyridine) towards methyl propiolate was carried out to analyze the influence of both the heteroatom (N, O, P, S) and the alkyl and/or aryl substituents of the Y ligand on the nature of the product obtained. The methyl substituent tends to accelerate the reactions. However, an aromatic ring bonded to N and O makes the reaction more difficult, whereas its linkage to P and S favour it. On the whole, ligands with O and S heteroatoms seem to disfavour these processes more than ligands with N and P heteroatoms, respectively. Phosphido and thiolato ligands tend to yield a coupling product with the bipy ligand, which is not the general case for hydroxo, alcoxo or amido ligands. When the Y ligand has an O/N and an H atom the most likely product is the one containing a coupling with the carbonyl ligand, which is not always obtained when Y contains P/S. Only for OMe and OPh, the product resulting from formal insertion into the Re-Y bond is the preferred.

Regiochemistry Control by Bipyridine Substituents in the Deprotonation of ReI and MoII N-Alkylimidazole Complexes.

Compounds containing N-alkylimidazoles (N-RIm) and 4,4'-disubstituted 2,2'-bipyridines (4,4'-R'2 bipy) coordinated to cationic {Mo(η3 -C4 H7 )(CO)2 } and {Re(CO)3 } fragments undergo deprotonation of the C2-H group of the N-RIm ligands in their reactions with KN(SiMe3 )2 . The resulting internal nucleophile adds either to one pyridyl ring, which becomes dearomatized and can undergo ring opening in the subsequent reaction with excess MeOTf, or to the metal center, yielding imidazol-2-yl complexes, which in turn add HOTf or MeOTf, affording N-heterocyclic carbene complexes. Which pathway is followed is dictated by the metal and the nature of the imidazole (R) and bipyridine (R') substituents. For ReI compounds, addition to pyridine is found with R'=tBu and OMe, whereas for R=Me and R'=NMe2 , imidazolyl formation is preferred. Coordination of 4,7-Cl2 -1,10-phenanthroline to MoII favors C-C coupling, in contrast to the analogous parent bipy or phenanthroline complexes, for which formation of the imidazol-2-yl complexes had been found. DFT calculations showed the theoretically expected products in each case, and following their predictions new types of products were obtained experimentally.

Epidemiology, molecular characterisation and antimicrobial susceptibility of Neisseria gonorrhoeae isolates in Madrid, Spain, in 2016.

With the aim to elucidate gonococcal antimicrobial resistance (AMR)-risk factors, we undertook a retrospective analysis of the molecular epidemiology and AMR of 104 Neisseria gonorrhoeae isolates from clinical samples (urethra, rectum, pharynx and cervix) of 94 individuals attending a sexually transmitted infection clinic in Madrid (Spain) from July to October 2016, and explored potential links with socio-demographic, behavioural and clinical factors of patients. Antimicrobial susceptibility was determined by E-tests, and isolates were characterised by N. gonorrhoeae multi-antigen sequence typing. Penicillin resistance was recorded for 15.4% of isolates, and most were susceptible to tetracycline, cefixime and azithromycin; a high incidence of ciprofloxacin resistance (~40%) was found. Isolates were grouped into 51 different sequence types (STs) and 10 genogroups (G), with G2400, ST5441, ST2318, ST12547 and G2992 being the most prevalent. A significant association (P = 0.015) was evident between HIV-positive MSM individuals and having a ciprofloxacin-resistant strain. Likewise, a strong association (P = 0.047) was found between patient age of MSM and carriage of isolates expressing decreased susceptibility to azithromycin. A decrease in the incidence of AMR gonococcal strains and a change in the strain populations previously reported from other parts of Spain were observed. Of note, the prevalent multi-drug resistant genogroup G1407 was represented by only three strains in our study, while the pan-susceptible clones such as ST5441, and ST2318, associated with extragenital body sites were the most prevalent.

Unexpected dynamical effects change the lambda-doublet propensity in the tunneling region for the O(3P) + H2 reaction.

One of the most relevant features of the O(3P) + H2 reaction is that it occurs on two different potential energy surfaces (PESs) of symmetries A' and A'' that correlate reactants and products. The respective saddle points, which correspond to a collinear arrangement, are the same for both PESs, whilst the barrier height rises more abruptly on the 3A' PES than on the 3A'' PES. Accordingly, the reactivity on the 3A'' PES should be always higher than on the 3A' PES. In this work, we present accurate quantum-scattering calculations showing that this is not always the case for rotationless reactants, where dynamical factors near the reaction threshold cause the 3A' PES to dominate at energies around the barrier. Further calculation of cross sections and Λ-doublet populations has allowed us to establish how the reaction mechanism changes from the deep tunneling regime to hyperthermal energies.

How reactant polarization can be used to change the effect of interference on reactive collisions.

It is common knowledge that integral and differential cross sections (DCSs) are strongly dependent on the spatial distribution of the molecular axis of the reactants. Hence, by controlling the axis distribution, it is possible to either promote or hinder the yield of products into specific final states or scattering angles. This idea has been successfully implemented in experiments by polarizing the internuclear axis before the reaction takes place, either by manipulating the rotational angular distribution or by the Stark effect in the presence of an orienting field. When there is a dominant reaction mechanism, characterized by a set of impact parameters and angles of attack, it is expected that a preparation that helps the system to reach the transition state associated with that mechanism will promote the reaction, whilst a different preparation would generally impair the reaction. However, when two or more competing mechanisms via interference contribute to the reaction into specific scattering angles and final states, it is not evident which would be the effect of changing the axis preparation. To address this problem, throughout this article we have simulated the effect that different experimental preparations have on the DCSs for the H + D2 reaction at relatively high energies, for which it has been shown that several competing mechanisms give rise to interference that shapes the DCS. To this aim, we have extended the formulation of the polarization dependent DCS to calculate polarization dependent generalized deflection functions of ranks greater than zero. Our results show that interference is very sensitive to changes in the internuclear axis preparation, and that the shape of the DCS can be controlled exquisitely.

New Stress Test for Ring Polymer Molecular Dynamics: Rate Coefficients of the O(3P) + HCl Reaction and Comparison with Quantum Mechanical and Quasiclassical Trajectory Results.

In the past decade, ring polymer molecular dynamics (RPMD) has emerged as a very efficient method to determine thermal rate coefficients for a great variety of chemical reactions. This work presents the application of this methodology to study the O(3P) + HCl reaction, which constitutes a stringent test for any dynamical calculation due to rich resonant structure and other dynamical features. The rate coefficients, calculated on the 3A' and 3A″ potential energy surfaces (PESs) by Ramachandran and Peterson [ J. Chem. Phys. 2003 , 119 , 9590 ], using RPMD and quasiclassical trajectories (QCT) are compared with the existing experimental and the quantum mechanical (QM) results by Xie et al. [ J. Chem. Phys. 2005 122 , 014301 ]. The agreement is very good at T > 600 K, although RPMD underestimates rate coefficients by a factor between 4 and 2 in the 200-500 K interval. The origin of these discrepancies lies in the large contribution from tunneling on the 3A″ PES, which is enhanced by resonances due to quasibound states in the van der Waals wells. Although tunneling is fairly well accounted for by RPMD even below the crossover temperature, the effect of resonances, a long-time effect, is not included in the methodology. At the highest temperatures studied in this work, 2000-3300 K, the RPMD rate coefficients are somewhat larger than the QM ones, but this is shown to be due to limitations in the QM calculations and the RPMD are believed to be more reliable.

Λ-Doublet Propensities for Reactions on Competing A' and A″ Potential Energy Surfaces: O(3 P) + N2 and O(3 P) + HCl.

This work presents scattering calculations for the O(3 P) + N2(1Σ) → NO(2Π) + N(4S) and for the O(3 P) + HCl(1Σ) → OH(2Π) + Cl(2P) reactions with a focus on the prediction of the Λ-doublet populations in which NO and OH are produced. Both reactions can take place on two competing potential energy surfaces of symmetries 3 A' and 3 A″ that correlate reagents with products but with very distinct topographies. As a result, they exhibit very different dynamical behaviors and total reactivity. Using a method that relates the reaction yield on the two competing surfaces to the Λ-doublet populations through the explicit consideration of the stereodynamics of the reaction, we predict that the population of NO and OH on the two Λ-doublet sates is surprisingly similar for both systems. These results contradict the model that assumes that collisions on the 3 A' and 3 A″ would give rise to products in the Π( A') and Π( A″) states, respectively.

Phosphinous Acid-Assisted Hydration of Nitriles: Understanding the Controversial Reactivity of Osmium and Ruthenium Catalysts.

The synthesis and catalytic behavior of the osmium(II) complexes [OsCl2 (η6 -p-cymene)(PR2 OH)] [R=Me (2 a), Ph (2 b), OMe (2 c), OPh (2 d)] in nitrile hydration reactions is presented. Among them, the best catalytic results were obtained with the phosphinous acid derivative [OsCl2 (η6 -p-cymene)(PMe2 OH)] (2 a), which selectively provided the desired primary amides in excellent yields and short times at 80 °C, employing directly water as solvent, and without the assistance of any basic additive (TOF values up to 200 h-1 ). The process was successful with aromatic, heteroaromatic, aliphatic, and α,ß-unsaturated organonitriles, and showed a high functional group tolerance. Indeed, complex 2 a represents the most active and versatile osmium-based catalyst for the hydration of nitriles reported so far in the literature. In addition, it exhibits a catalytic performance similar to that of its ruthenium analogue [RuCl2 (η6 -p-cymene)(PMe2 OH)] (4). However, when compared to 4, the osmium complex 2 a turned out to be faster in the hydration of less-reactive aliphatic nitriles, whereas the opposite trend was generally observed with aromatic substrates. DFT calculations suggest that these differences in reactivity are mainly related to the ring strain associated with the key intermediate in the catalytic cycle, that is, a five-membered metallacyclic species generated by intramolecular addition of the hydroxyl group of the phosphinous acid ligand to the metal-coordinated nitrile.

Insights on the Reactivity of Terminal Phosphanido Metal Complexes toward Activated Alkynes from Theoretical Computations.

Herein we present a theoretical study on the reaction of [Re(PPh2) (CO)3(phen)] (phen = 1,10-phenanthroline) and [Re(PPh2) (CO)3(bipy)] (bipy = 2,2'-bipyridine) toward methyl propiolate. In agreement with experimental results for the phen ligand, the coupling of the substituted acetylenic carbon with the nonsubstituted ortho carbon of the phen ligand is the preferred route from both kinetic and thermodynamic viewpoints with a Gibbs energy barrier of 18.8 kcal/mol and an exoergicity of 11.1 kcal/mol. There are other two routes, the insertion of the acetylenic fragment into the P-Re bond and the coupling between the substituted acetylenic carbon and a carbonyl ligand in cis disposition, which are kinetically less favorable than the preferred route (by 2.8 and 1.9 kcal/mol, respectively). Compared with phen, the bipy ligand shows less electrophilic character and also less π electron delocalization due to the absence of the fused ring between the two pyridine rings. As a consequence, the route involving the coupling with a carbonyl ligand starts to be kinetically competitive, whereas the product of the attack to bipy is still the most stable and would be the one mainly obtained after spending enough time to reach thermal equilibrium.

The dynamics of the Hg + Br2 reaction: elucidation of the reaction mechanism for the Br exchange reaction.

In spite of its importance in the Hg atmospheric chemistry, the dynamics of the Hg + Br2 → HgBr + Br reaction is poorly understood. In this article, we have carried out a comprehensive study of the reaction mechanism of this reaction by means of quasiclassical trajectories (QCTs) on an existing ab initio potential energy surface (PES). The reaction has a non trivial dynamics, as a consequence of its large endothermicity, the presence of a deep potential well, and the competition between the Br exchange and the collision induced dissociation processes. Our calculations demonstrate that insertion is only relevant at energies just above the reaction threshold and that, at energies above 2.3 eV, HgBr formation typically takes place via a sort of frustrated dissociation. In order to compare directly with the results obtained in extensive cross molecular beam experiments for the homologous reaction with I2, angular distributions in the laboratory frame for Hg + Br2 have been simulated under similar experimental conditions. The lack of agreement at the highest energies considered suggests that either the two reactions have substantially different mechanisms or that calculations on a single PES cannot account for the dynamics at those energies.