ABSTRACT
After optimization for retention of catalytic activity, 4-chlorobenzoic acid emerged as the optimal catalyst for the aliphatic ketone Claisen rearrangement. The optimal catalyst enables a one-pot, metal-free, catalytic protocol from allylic alcohols to γ,δ-unsaturated ketones. The optimized process tolerates a range of substrates, including substituents with acid-labile protecting groups. Reaction monitoring and DFT studies of the aliphatic ketone Claisen process agree that the ultimate rearrangement step typically has the highest activation barrier.
ABSTRACT
Early invasive skin melanoma (EISM) associated with partial tumor invasion to the thin and optically complex papillary dermis (PD) represents a critical stage before the onset of metastasis. EISM lesions may be accompanied by angiogenesis, which can alter the PD's blood and fibril contents. A comprehensive understanding about these interconnected processes is essential for enhancing the efficacy of EISM optical evaluation methodologies. Employing a first-principles computational approach supported by measured data, we systematically assess the impact that angiogenesis can have on the EISM's spectral responses. Our findings indicate that these responses are discernibly affected by angiogenesis under distinct physiological conditions, with more substantial tissue alterations leading to accentuated spectral changes in the 550-600 nm region. Accordingly, we propose the use of a customized low-cost spectral index to monitor these processes. Furthermore, our investigation provides a high-fidelity in silico platform for interdisciplinary research on the photobiology of evolving skin melanomas.
ABSTRACT
One of the overarching goals in nuclear science is to understand how the nuclear chart emerges from the underlying fundamental interactions. The description of the structure of nuclei from first principles, using ab initio methods for the solution of the many-nucleon problem with inputs from chiral effective field theory, has advanced dramatically over the past two decades. We present an overview over the available ab initio tools with a specific emphasis on electromagnetic observables, such as multipole moments and transition strengths. These observables still pose a challenge for ab initio theory and are one of the most exciting domains to exploit synergies with modern experiments. Precise experimental data are vital for the validation of the theory predictions and the refinement of ab initio methods. We discuss some of the past and future experimental efforts highlighting these synergies. This article is part of the theme issue 'The liminal position of Nuclear Physics: from hadrons to neutron stars'.
ABSTRACT
Humilisin E is a diterpenoid possessing a rare epoxidized cyclononene trans-fused with a bicyclo[3.2.0]heptane core. We have identified the P atropisomer of the corresponding cyclononadiene as a potential biosynthetic/synthetic precursor to humilisin E and reported two different strategies for the stereocontrolled synthesis of the appropriately functionalized bicyclic cores of humilisin E. The first route involves a Stork epoxynitrile cyclization via a Mg alkoxide, and the second, more stereoselective approach utilizes the Wolff rearrangement as the key step.
ABSTRACT
Pyridoxal hydrochloride, a vitamin B6 vitamer, was synthetically converted to a series of diverse redox-active benzoyl pyridinium salts. Cyclic voltammetry studies demonstrated redox reversibility under basic conditions, and two of the most promising salts were subjected to laboratory-scale flow battery tests involving galvanostatic cycling at 10â mM in 0.1â M NaOH. In these tests, the battery was charged completely, corresponding to the transfer of two electrons to the electrolyte, but no discharge was observed. Both CV analysis and electrochemical simulations confirmed that the redox wave observed in the experimental voltammograms corresponds to a two-electron process. To explain the irreversibility in the battery tests, we conducted bulk electrolysis with the benzoyl pyridinium salts, affording the corresponding benzylic secondary alcohols. Computational studies suggest that the reduction proceeds in three consecutive steps: first electron transfer (ET), then proton-coupled electron transfer (PCET) and finally proton transfer (PT) to give the secondary alcohol. 1Hâ NMR deuterium exchange studies indicated that the last PT step is not reversible in 0.1â M NaOH, rendering the entire redox process irreversible. The apparent reversibility observed in CV at the basic media likely arises from the slow rate of the PT step at the timescale of the measurement.
ABSTRACT
A carboxylate-catalyzed, metal-free C-silylation protocol for terminal alkynes is reported using a quaternary ammonium pivalate as the catalyst and commercially available N,O-bis(silyl)acetamides as silylating agents. The reaction proceeds under mild conditions, tolerates a range of functionalities, and enables concomitant O- or N-silylation of acidic OH or NH groups. A Hammett ρ value of +1.4 ± 0.1 obtained for para-substituted 2-arylalkynes is consistent with the proposed catalytic cycle involving a turnover-determining deprotonation step.
ABSTRACT
Material appearance is largely determined by complex light attenuation processes. The distinct bluish colorations that can be observed when light is transmitted through snow are among the most striking outcomes of these processes. In this article, we present a method for the predictive rendering of this phenomenon taking into account the variability of snow's physical and morphological characteristics. To achieve that, we employ an approach centered on the effective use of spectral transmittance data obtained using a first-principles light transport model for snow. The suitability of the proposed method to rendering applications is illustrated through the synthesis of images depicting the bluish appearance of snow under different illumination conditions.
ABSTRACT
A mild catalytic variant of the aldol reaction between ethyl diazoacetate and aldehydes is described using a combination of N,O-bis(trimethylsilyl)acetamide and catalytic tetramethylammonium pivalate as catalyst. The reaction proceeds rapidly at ambient temperature to afford the O-silylated aldol products in good to excellent yield, and the acetamide byproducts can be removed by simple filtration.
ABSTRACT
N-functionalized pyridinium frameworks derived from the three major vitamers of vitamin B6, pyridoxal, pyridoxamine and pyridoxine, have been screened computationally for consideration as negative electrode materials in aqueous organic flow batteries. A molecular database including the structure and the one-electron standard reduction potential of related pyridinium derivatives has been generated using a computational protocol that combines semiempirical and DFT quantum chemical methods. The predicted reduction potentials span a broad range for the investigated pyridinium frameworks, but pyridoxal derivatives, particularly those involving electron withdrawing substituents, have potentials compatible with the electrochemical stability window of aqueous electrolytes. The stability of radicals formed upon one-electron reduction has been analyzed by a new computational tool proposed recently for large-scale computational screening.
ABSTRACT
The atomic masses of ^{55}Sc, ^{56,58}Ti, and ^{56-59}V have been determined using the high-precision multireflection time-of-flight technique. The radioisotopes have been produced at RIKEN's Radioactive Isotope Beam Factory (RIBF) and delivered to the novel designed gas cell and multireflection system, which has been recently commissioned downstream of the ZeroDegree spectrometer following the BigRIPS separator. For ^{56,58}Ti and ^{56-59}V, the mass uncertainties have been reduced down to the order of 10 keV, shedding new light on the N=34 shell effect in Ti and V isotopes by the first high-precision mass measurements of the critical species ^{58}Ti and ^{59}V. With the new precision achieved, we reveal the nonexistence of the N=34 empirical two-neutron shell gaps for Ti and V, and the enhanced energy gap above the occupied νp_{3/2} orbit is identified as a feature unique to Ca. We perform new Monte Carlo shell model calculations including the νd_{5/2} and νg_{9/2} orbits and compare the results with conventional shell model calculations, which exclude the νg_{9/2} and the νd_{5/2} orbits. The comparison indicates that the shell gap reduction in Ti is related to a partial occupation of the higher orbitals for the outer two valence neutrons at N=34.
Subject(s)
Neutrons , TitaniumABSTRACT
Changes in skin appearance are among the most recognizable symptoms of a number of medical conditions. The interpretation of such changes, however, may be inadvertently biased by normal physiological processes affecting skin optical properties. In this paper, we assess the impact of one of the most common of these processes, tanning, on variations in skin chromatic attributes elicited by two ubiquitous and serious medical conditions, anemia and hyperbilirubinemia. We employ a first-principles investigation approach centered on the use of predictive computer simulations of light and skin interactions, and on well-established colorimetry methods. In our in silico experiments, we considered skin chromatic attributes resulting from distinct anemia severity levels and hyperbilirubinemia tox-icity stages. Our findings highlight qualitative and quantitative aspects that need to be considered in the visual screening and monitoring of these conditions, notably when they occur with the concomitant presence of tanning-induced changes in the cutaneous tissues' melanin pigmentation and thickness.
Subject(s)
Anemia , Skin Pigmentation , Colorimetry , Humans , Hyperbilirubinemia , SkinABSTRACT
Dithienosilole moiety is an electron donating unit, and it has been applied, for example, as a part of small molecular and polymeric electron donors in high performance organic photovoltaic cells. Herein, we report efficient synthetic routes to two symmetrical, dithienosilolo-central-unit-based A-D-A type organic semiconducting materials DTS(Th 2 FBTTh) 2 and DTS(ThFBTTh) 2 . Fine-tuned conditions in Suzuki-Miyaura couplings were tested and utilized. The effect of inserting additional hexylthiophene structures symmetrically into the material backbone was investigated, and it was noted that contrary to commonly accepted fact, the distance between electron donor and acceptor seems to play a bigger role in lowering the E gap value of the molecule than just extending the length of the conjugated backbone. We searched for precedent cases from the literature, and these are compared to our findings. The optical properties of the materials were characterized with UV-vis spectroscopy. Majority of the intermediate compounds along the way to final products were produced with excellent yields. Our results offer highly efficient routes to many heterocyclic structures but also give new insights into the design of organic semiconducting materials.
ABSTRACT
We demonstrate herein the capacity of simple carboxylate salts - tetrametylammonium and tetramethylguanidinium pivalate - to act as catalysts in the isomerization of ß,γ-unsaturated thioesters to α,ß-unsaturated thioesters. The carboxylate catalysts gave reaction rates comparable to those obtained with DBU, but with fewer side reactions. The reaction exhibits a normal secondary kinetic isotope effect (k1H /k1D =1.065±0.026) with a ß,γ-deuterated substrate. Computational analysis of the mechanism provides a similar value (k1H /k1D =1.05) with a mechanism where γ-reprotonation of the enolate intermediate is rate determining.
Subject(s)
Carboxylic Acids , Isotopes , Catalysis , Isomerism , KineticsABSTRACT
BACKGROUND: In SLE, low complement is an important serological manifestation. Recent classification criteria include hypocomplementemia and one gives additional weight if both C3 and C4 are low. We evaluated patients with a history of, and those with persistently, low complement. As complement activation occurs in the antiphospholipid antibody syndrome, an analysis was also performed on those with positive antiphospholipid antibodies to evaluate thrombotic outcomes. METHODS: In a longitudinal SLE cohort, organ manifestations, damage, C3, C4 and antiphospholipid antibodies were assessed quarterly. Using univariate and multivariate methods we compared those with and without a history of low C3, low C4 and both. We evaluated those who had a history of low complement at any time point, and those who had persistent hypocomplementemia. Further analysis considered thrombotic outcomes in patients with positive antiphospholipid antibodies and a history of low complement. RESULTS: 2399 patients were evaluated. Fifty-five percent had a history of low C3 and 47% low C4; 83 (4%) had persistently low C3 and 65 (3.2%) had persistently low C4. Hematological, renal and serological abnormalities associated with a history of low C3 but not low C4. With anticardiolipin antibodies, a history of hypocomplementemia (both C3 and C4 low) associated with stroke and deep venous thrombosis. CONCLUSION: Low C4 was a weak marker in terms of the associated clinical and serological manifestations. Low C3 associated with renal involvement and poor renal outcomes. A history of both low C3 and C4 associated with stroke in the presence of lupus anticoagulant or anticardiolipin antibodies, and low C4 with digital gangrene (with lupus anticoagulant).
Subject(s)
Complement C4 , Lupus Erythematosus, Systemic , Antibodies, Antiphospholipid , Complement C3 , Humans , Lupus Coagulation Inhibitor , Lupus Erythematosus, Systemic/complicationsABSTRACT
A stereoselectivity model inspired by the total synthesis of stemona alkaloids is developed to explain why enolate-derived 3,4-fused butyrolactones are methylated with a preference for syn alkylation. The model shows how conformational locking present in nonplanar enolate structures favors syn over anti methylation, due to less significant structural distortions in the syn pathway. The developed model was also successfully used to rationalize selectivities of previously documented methylation reactions.
ABSTRACT
A concise enantio- and stereocontrolled synthesis of (+)-lycoperdic acid is presented. The stereochemical control is based on iminium-catalyzed Mukaiyama-Michael reaction and enamine-catalyzed organocatalytic α-chlorination steps. The amino group was introduced by azide displacement, affording the final stereochemistry of (+)-lycoperdic acid. Penultimate hydrogenation and hydrolysis afforded pure (+)-lycoperdic acid in seven steps from a known silyloxyfuran.
Subject(s)
Imines/chemistry , Lactones/chemical synthesis , Catalysis , Lactones/chemistry , Molecular Structure , StereoisomerismABSTRACT
Photoactivation in the Photoactive Yellow Protein, a bacterial blue-light photoreceptor, proceeds via photoisomerization of the double CâC bond in the covalently attached chromophore. Quantum chemistry calculations, however, have suggested that in addition to double-bond photoisomerization, the isolated chromophore and many of its analogues can isomerize around a single C-C bond as well. Whereas double-bond photoisomerization has been observed with X-ray crystallography, experimental evidence of single-bond photoisomerization is currently lacking. Therefore, we have synthesized a chromophore analogue, in which the formal double bond is covalently locked in a cyclopentenone ring, and carried out transient absorption spectroscopy experiments in combination with nonadiabatic molecular dynamics simulations to reveal that the locked chromophore isomerizes around the single bond upon photoactivation. Our work thus provides experimental evidence of single-bond photoisomerization in a photoactive yellow protein chromophore analogue and suggests that photoisomerization is not restricted to the double bonds in conjugated systems. This insight may be useful for designing light-driven molecular switches or motors.
Subject(s)
Photochemistry/methods , Proteins/chemistry , Bisphenol A-Glycidyl Methacrylate , HumansABSTRACT
Spectroscopic factors of neutron-hole and proton-hole states in ^{131}Sn and ^{131}In, respectively, were measured using one-nucleon removal reactions from doubly magic ^{132}Sn at relativistic energies. For ^{131}In, a 2910(50)-keV γ ray was observed for the first time and tentatively assigned to a decay from a 5/2^{-} state at 3275(50) keV to the known 1/2^{-} level at 365 keV. The spectroscopic factors determined for this new excited state and three other single-hole states provide first evidence for a strong fragmentation of single-hole strength in ^{131}Sn and ^{131}In. The experimental results are compared to theoretical calculations based on the relativistic particle-vibration coupling model and to experimental information for single-hole states in the stable doubly magic nucleus ^{208}Pb.
ABSTRACT
P25 comprising of mixed anatase and rutile phases is known to be highly photocatalytically active compared to the individual phases. Using a facile wet chemical method, we demonstrate a ternary nanocomposite consisting of Ni and Ag nanoparticles, decorated on the surface of XTiO2 (X: P25, rutile (R)) as an efficient visible-light-driven photocatalyst. Contrary to the current perspective, RTiO2-based Ni-Ag-RTiO2 shows the highest activity with the H2 evolution rate of â¼86 µmol g-1 W-1 h-1@535 nm. Together with quantitative assessment of active Ni, Ag and XTiO2 in these ternary systems using high energy synchrotron X-ray diffraction, transmission electron microscopy coupled energy dispersive spectroscopy mapping evidences the metal to semiconductor contact via Ag. The robust photocatalytic activity is attributed to the improved visible light absorption, as noted by the observed band edge of â¼2.67 eV corroborating well with the occurrence of Ti3+ in Ti 2p XPS. The effective charge separation due to intimate contact between Ni and RTiO2 via Ag is further evidenced by the plasmon loss peak in Ag 3d XPS. Moreover, density functional theory calculations revealed enhanced adsorption of H2 on Ti8O16 clusters when both Ag and Ni are simultaneously present, owing to the hybridization of the metal atoms with d orbitals of Ti and p orbitals of O leading to enhanced bonding characteristics, as substantiated by the density of states. Additionally, the variation in the electronegativity in Bader charge analysis indicates the possibility of hydrogen evolution at the Ni sites, in agreement with the experimental observations.
ABSTRACT
AIM: The Lupus Low Disease Activity State (LLDAS) is a potential treat to target goal in systemic lupus erythematosus (SLE). SLE patients in LLDAS for more than half of the observation time have about a 50% lower risk of new organ damage and have reduced mortality. We identified predictors of being in LLDAS ≥50% of the observation time. METHODS: A total of 2228 SLE patients who had at least three clinical visits were included. Percentage of time in LLDAS was calculated based on the proportion of days under observation. LLDAS-50 was defined as being in LLDAS for ≥50% of the observation time. We used the stepwise selection procedure in logistic regression to identify predictors of LLDAS-50. RESULTS: A total of 1169 (52.5%) SLE patients, but only 37.6% of African Americans, achieved LLDAS-50. In the multivariable model, African American ethnicity, hypocomplementemia, serositis, renal activity, arthritis, anti-RNP, anti-dsDNA, vasculitis, malar rash, discoid rash, thrombocytopenia, and immunosuppressive use were negative predictors of LLDAS-50. Older age at diagnosis, longer disease duration, higher education level, and greater percentage of time taking hydroxychloroquine remained positive predictors of LLDAS-50. CONCLUSION: In this large cohort, only 52.5% achieved LLDAS-50. This proportion was even less in African Americans. A higher percentage of time taking hydroxychloroquine was a modifiable positive predictor of LLDAS-50. Anti-RNP, anti-dsDNA, and low complement were negatively associated with LLDAS-50. Our findings further emphasize the importance of inclusion of African Americans in clinical trials and hydroxychloroquine adherence in both clinical practice and clinical trials.