Syn vs. Anti? What Controls Addition Stereochemistry in Chlorolactonization.

The stereochemistry of the uncatalyzed chlorolactonization of 4-phenylpent-4-enoic acid at room temperature was examined to probe the reaction's intrinsic diastereoselectivities as a function of chlorenium ion donor, solvent polarity, and reactant concentration ranges. Kinetic studies using Variable Time Normalization Analysis (VTNA) revealed differing reaction orders for the syn and anti alkene addition processes. Aided and illustrated by quantum chemical modeling, this detailed mechanistic analysis of the substrate's intrinsic chlorolactonization reactions points to concerted Ad3-type paths for both syn and anti additions.

Mechanistic Insight into the Thermal "Blueing" of Cyanine Dyes.

In recent work to develop cyanine dyes with especially large Stokes shifts, we encountered a "blueing" reaction, in which the heptamethine cyanine dye (IUPAC: 1,3,3-trimethyl-2-((1,3,5)-7-(()-1,3,3-trimethylindolin-2-ylidene)hepta-1,3,5-trien-1-yl)-3-indol-1-ium) undergoes shortening in two-carbon steps to form the pentamethine () and trimethine () analogs. Each step blue-shifts the resulting absorbance wavelength by ca. 100 nm.

Bronchial artery embolization using small particles is safe and effective: a single center 12-year experience.

Background: Bronchial artery embolization (BAE) using particles is an established treatment for hemoptysis. The use of polyvinyl alcohol (PVA) with a particle size of 300 µm or larger is thought to reduce the risk of non-target embolization but may result in more proximal vessel occlusion than is ideal, resulting in a high rate of early recurrent hemorrhage.

Objective: This study evaluates the safety and efficacy of BAE using PVA particles with a size of less than 300 µm.

Patient-Reported Symptom Severity, Health-Related Quality of Life, and Emotional Distress Trajectories During and After Radiation Therapy for Human Papillomavirus-Associated Oropharyngeal Cancer: A TROG 12.01 Secondary Analysis.

Purpose: This secondary analysis of clinical trial TROG 12.01, involving patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma, aimed to identify patient-reported outcome (PRO) trajectories before, during, and after chemoradiotherapy.

Methods And Materials: Head and neck cancer symptom severity (HNSS) and interference (HNSI), generic health-related quality of life (HRQL), and emotional distress were assessed with the MD Anderson Symptom Inventory-Head and Neck, Functional Assessment of Cancer Therapy-General, and Hospital Anxiety and Depression Scale questionnaires, respectively.

Structure-Enantioselectivity Relationship (SER) Study of Cinchona Alkaloid Chlorocyclization Catalysts.

Various structural elements of the Cinchona alkaloid dimers are interrogated to establish a structure-enantioselectivity relationship (SER) in three different halocyclization reactions. SER for chlorocyclizations of a 1,1-disubstituted alkenoic acid, a 1,1-disubstituted alkeneamide, and a -1,2-disubstituted alkeneamide showed variable sensitivities to linker rigidity and polarity, aspects of the alkaloid structure, and the presence of two or only one alkaloid side group defining the catalyst pocket. The conformational rigidity of the linker-ether connections was probed via DFT calculations on the methoxylated models, uncovering especially high barriers to ether rotation out of plane in the arene systems that include the pyridazine ring.

Infrared quantification of ethanol and 1-butanol hydrogen bonded hydroxyl distributions in cyclohexane.

Quantifying the mid-range infrared hydroxyl stretch absorbance region has traditionally been a challenge due to the wavenumber dependence of the attenuation coefficient. Interpretation often assigns a single attenuation coefficient to each type of hydrogen-bonded aggregate. This work leverages a recently developed technique of scaling hydroxyl stretching absorbances in the mid-infrared region with a continuous attenuation coefficient function that produces integrated areas which directly correlate to hydroxyl concentrations.

Patient- and Clinician-Reported Outcomes in Human Papillomavirus-Associated Tonsillar Carcinoma Treated With Unilateral and Bilateral Intensity Modulated Radiation Therapy-A Substudy From TROG 12.01.

Purpose: The aim of this TROG 12.01 substudy was to report longitudinal variations in patient- (PRO) and clinician-reported outcomes based on receipt of unilateral (URT) or bilateral radiation therapy (BRT).

Methods And Materials: Patients with lateralized T1-2 N1-2b human papillomavirus-associated tonsillar carcinoma (AJCC7) enrolled on TROG 12.

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown.

Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC.

Design, Setting, And Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020.

Skeletal Ni electrode-catalyzed C-O cleavage of diaryl ethers entails direct elimination via benzyne intermediates.

Diaryl ethers undergo electrocatalytic hydrogenolysis (ECH) over skeletal Ni cathodes in a mild, aqueous process that achieves direct C-O cleavage without initial benzene ring saturation. Mechanistic studies find that aryl phenyl ethers with a single para or meta functional group (methyl, methoxy, or hydroxy) are selectively cleaved to the substituted benzene and phenol, in contrast to recently reported homogeneous catalytic cleavage processes. Ortho positioning of substituents reverses this C-O bond selectivity, except for the 2-phenoxyphenol case.

Contemporary Multimodality Imaging of Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a disorder characterized by hypercalcemia and an elevated or inappropriately normal parathyroid hormone level. Classic features include bone pain, fractures, renal impairment, nephrolithiasis, and mental disturbance. However, most cases of PHPT are now asymptomatic at diagnosis or associated with nonspecific neurocognitive changes.

Intramolecular Relaxation Dynamics Mediated by Solvent-Solute Interactions of Substituted Fluorene Derivatives. Solute Structural Dependence.

Several fluorene derivatives exhibit excited-state reactivity and relaxation dynamics that remain to be understood fully. We report here the spectral relaxation dynamics of two fluorene derivatives to evaluate the role of structural modification in the intramolecular relaxation dynamics and intermolecular interactions that characterize this family of chromophores. We have examined the time-resolved spectral relaxation dynamics of two compounds, NCy- and MK-, in protic and aprotic solvents using steady-state and time-resolved emission spectroscopy and quantum chemical computations.

Excited-State Dynamics of a Substituted Fluorene Derivative. The Central Role of Hydrogen Bonding Interactions with the Solvent.

Substituted fluorene structures have demonstrated unusual photochemical properties. Previous reports on the substituted fluorene Schiff base -SB demonstrated super photobase behavior with a Δp of ∼14 upon photoexcitation. In an effort to understand the basis for this unusual behavior, we have examined the electronic structure and relaxation dynamics of the structural precursor of -SB, the aldehyde , in protic and aprotic solvents using time-resolved fluorescence spectroscopy and quantum chemical calculations.

Femtosecond dynamics and coherence of ionic retro-Diels-Alder reactions.

Ultrafast tunnel ionization enables femtosecond time-resolved dynamic measurements of the retro-Diels-Alder reactions of positively charged cyclohexene, norbornene, and dicyclopentadiene. Unlike the reaction times of 500-600 ps that are observed following UV excitation of neutral species, on the ionic potential energy surfaces, these reactions occur on a single picosecond timescale and, in some cases, exhibit vibrational coherence. In the case of norbornene, a 270 cm vibrational mode is found to modulate the retro-Diels-Alder reaction.

A chiroptical approach for the absolute stereochemical determination of -stereogenic centers.

A simple chiroptical solution for the absolute stereochemical determination for asymmetric phosphorus V stereocenters is presented. Strong coordination of the phosphorus oxide with the Zn-metallo center of the racemic host Zn-MAPOL leads to an induced axial chirality of the host, yielding a strong ECCD signal. A mnemonic is proposed to correlate the asymmetry of the guest molecule with the observed ECCD signal.

Randomized Trial of Radiation Therapy With Weekly Cisplatin or Cetuximab in Low-Risk HPV-Associated Oropharyngeal Cancer (TROG 12.01) - A Trans-Tasman Radiation Oncology Group Study.

Purpose: The excellent prognosis of patients with low-risk human papillomavirus (HPV)- associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiation therapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an epidermal growth factor receptor targeting antibody, when combined with radiation therapy would result in a decrease in symptom burden and toxicity with similar efficacy compared with weekly cisplatin.

Methods And Materials: TROG12.

Isoenergetic two-photon excitation enhances solvent-to-solute excited-state proton transfer.

Two-photon excitation (TPE) is an attractive means for controlling chemistry in both space and time. Since isoenergetic one- and two-photon excitations (OPE and TPE) in non-centrosymmetric molecules are allowed to reach the same excited state, it is usually assumed that they produce similar excited-state reactivity. We compare the solvent-to-solute excited-state proton transfer of the super photobase FR0-SB following isoenergetic OPE and TPE.

Steric effects in light-induced solvent proton abstraction.

The significance of solvent structural factors in the excited-state proton transfer (ESPT) reactions of Schiff bases with alcohols is reported here. We use the super photobase FR0-SB and a series of primary, secondary, and tertiary alcohol solvents to illustrate the steric issues associated with solvent to photobase proton transfer. Steady-state and time-resolved fluorescence data show that ESPT occurs readily for primary alcohols, with a probability proportional to the relative -OH concentration.

Validation of local p16 testing for determination of human papilloma virus status eligibility on a low risk oropharyngeal cancer trial - A Trans-Tasman Radiation Oncology Group study.

Objective: Accurate determination of human papilloma virus (HPV) status is critical when identifying patients with oropharyngeal squamous cell carcinoma (OPSCC) who may be candidates for de-escalation trials. In this study we investigated whether local p16 screening, by immunohistochemistry (IHC), has high positive predictive value (PPV) for HPV status in a good prognosis HPV positive OPSCC (HPVOPSCC) population treated on a clinical trial.

Methods And Materials: Patients enrolled on the TROG 12.

Gastrointestinal Bleeding in a Pancreas Transplant Recipient: A Case to Remember.

BACKGROUND Pancreas transplantation has proven to be the most effective therapeutic option for insulin-dependent diabetes mellitus. However, despite advances in surgical technique and continuously improving outcomes, pancreas transplantation has the highest complication rate among all solid-organ transplants. Vascular complications in particular can be catastrophic, with graft- and life-threatening potential.

Nucleophilic Thiols Reductively Cleave Ether Linkages in Lignin Model Polymers and Lignin.

Lignin may serve as a renewable feedstock for the production of chemicals and fuels if mild, scalable processes for its depolymerization can be devised. The use of small organic thiols represents a bioinspired strategy to cleave the β-O-4 bond, the most common linkage in lignin. In the present study, synthetic β-O-4 linked polymers were treated with organic thiols, yielding up to 90 % cleaved monomer products.

Greener Routes to Biomass Waste Valorization: Lignin Transformation Through Electrocatalysis for Renewable Chemicals and Fuels Production.

Lignin valorization is essential for biorefineries to produce fuels and chemicals for a sustainable future. Today's biorefineries pursue profitable value propositions for cellulose and hemicellulose; however, lignin is typically used mainly for its thermal energy value. To enhance the profit potential for biorefineries, lignin valorization would be a necessary practice.

Mechanistic Insights into the Origin of Stereoselectivity in an Asymmetric Chlorolactonization Catalyzed by (DHQD)PHAL.

Electrophilic halofunctionalization reactions have undergone a resurgence sparked by recent discoveries in the field of catalytic asymmetric halocyclizations. To build mechanistic understanding of these asymmetric transformations, a toolbox of analytical methods has been deployed, addressing the roles of catalyst, electrophile (halenium donor), and nucleophile in determining rates and stereopreferences. The test reaction, (DHQD)PHAL-catalyzed chlorocyclization of 4-arylpent-4-enoic acid with 1,3-dichloro-5,5-dimethylhydantoin (DCDMH), is revealed to be first order in catalyst and chlorenium ion donor and zero order in alkenoic acid substrate under synthetically relevant conditions.

Quantitative Analysis of Infrared Spectra of Binary Alcohol + Cyclohexane Solutions with Quantum Chemical Calculations.

Hydrogen bonding has profound effects on the behavior of molecules. Fourier-transform infrared spectroscopy is the technique most commonly used to qualitatively identify hydrogen-bonding moieties present in a chemical sample. However, quantitative analysis of infrared (IR) spectra is nontrivial for the hydroxyl stretching region where hydrogen bonding is most prominently expressed in organic alcohols and water.

Is prospective MRI mapping of the changes in the volume of the prostate gland in prostate cancer patients undergoing 6 months of neo-adjuvant androgen deprivation therapy a step towards a trial to determine those who may benefit from treatment intensification or extended duration?

Introduction: Neo-adjuvant androgen deprivation therapy prior to radiotherapy (RT) causes shrinkage of the prostate gland, but the changes in volume have never been mapped over time in detail, nor have the associations between volume reduction and testosterone escape or prostate-specific antigen (PSA) kinetics been determined.

Methods: Fifty consecutive patients with prostate cancer were treated with 6 months of triptorelin prior to definitive RT. The volume of the prostate gland was measured at the outset and every 6-7 weeks thereafter using MRI scans.