Hydrogen Isotope Labeling of Pharmaceuticals Via Dual Hydrogen Isotope Exchange Pathways Using CdS Quantum Dot Photocatalyst.

Isotopic labeling is a powerful technique extensively used in the pharmaceutical industry. By tracking isotope-labeled molecules, researchers gain unique and invaluable insights into the pharmacokinetics and pharmacodynamics of new drug candidates. Hydrogen isotope labeling is particularly important as hydrogen is ubiquitous in organic molecules in biological systems, and it can be introduced effectively through late-stage hydrogen isotope exchange (HIE).

Homogenous Palladium-Catalyzed Dehalogenative Deuteration and Tritiation of Aryl Halides with D/T Gas.

Hydrogen isotopically labeled compounds have extensive utility across diverse domains, especially in drug discovery and development. However, synthesis of the labeled compounds with exclusive site selectivity and/or high isotope incorporation is challenging. One widely employed method is heterogeneous palladium(0)-catalyzed (such as Pd/C) dehalogenative deuteration and tritiation with D/T gas.

Interplay between interparental relationship quality and infant temperament predicts toddler transdiagnostic psychopathology.

Although exposure to interparental conflict (IPC) in late childhood and adolescence appears to be a robust risk factor for the development of child psychopathology, less work has examined how very early exposure to IPC poses risk for the development of psychopathology in the first 2 years of life. Further, it is unclear whether IPC is uniquely related to child psychopathology relative to other critical dimensions of the interparental relationship. This study aimed to investigate the unique effects of IPC and low levels of emotional intimacy in the interparental relationship during pregnancy and infancy on toddler psychopathology and whether children with higher negative emotionality during infancy were most vulnerable to these conditions.

A General Strategy for N-(Hetero)arylpiperidine Synthesis Using Zincke Imine Intermediates.

Methods to synthesize diverse collections of substituted piperidines are valuable due to the prevalence of this heterocycle in pharmaceutical compounds. Here, we present a general strategy to access -(hetero)arylpiperidines using a pyridine ring-opening and ring-closing approach via Zincke imine intermediates. This process generates pyridinium salts from a wide variety of substituted pyridines and (heteroaryl)anilines; hydrogenation reactions and nucleophilic additions then access the -(hetero)arylpiperidine derivatives.

Early executive control buffers risk for adolescent psychopathology during the COVID-19 pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a global impact on youth mental health, and there is a critical need for research examining individual factors that contribute to increased psychopathology during the pandemic. The current study explored whether executive control (EC) abilities in early childhood interact with COVID-related stress to attenuate risk for adolescent psychopathology during the first 6 months of the pandemic.

Methods: Participants were 337 youth (49% female) living in a small midwestern city in the United States.

Does preschool executive control mediate the impact of early environmental unpredictability and deprivation on the general factor of psychopathology a decade later?

Background: Although deprivation has been consistently shown to increase risk for psychopathology through impaired executive control, the unique effects of other dimensions of early adversity, such as unpredictability, on executive control development are poorly understood. The current study evaluated whether deprivation and/or unpredictability early in life have unique effects on the general factor of psychopathology through impaired preschool executive control.

Methods: Participants included 312 children (51% female) oversampled for greater sociodemographic risk.

Learning from adversity: What the COVID-19 pandemic can teach us about family resiliency.

The present study aimed to characterize the immediate impacts of the COVID-19 pandemic on families with preschool age children and to identify pre-pandemic factors that explained unique family experiences. We leveraged an ongoing longitudinal study of relatively well-resourced community families who had reported on family functioning prior to the pandemic and completed surveys 6 months after pandemic onset. Both parents of dual parenting households endorsed significant hardships as a direct result of the pandemic (e.

Empirical support for a dual process model of the p-factor: Interaction effects between preschool executive control and preschool negative emotionality on general psychopathology.

Recent work indicates that a general factor, often referred to as the p-factor, underlies nearly all forms of psychopathology. Although the criterion validity and utility of this general factor have been well supported, questions remain about the substantive meaning of the p-factor. The purpose of the present longitudinal study was to empirically test the hypothesis that the p-factor reflects dysregulation arising from a combination of high dispositional negative emotionality and low executive control.

A Diastereoselective Method for the Construction of -2'-Deoxy-2'-fluoronucleosides.

A general and diastereoselective fluorination/glycosylation strategy for the synthesis of 2'-fluorinated nucleosides has been developed. Electrophilic fluorination of a glycal with NFSI provided the 1',2'-difunctionalized furanoside intermediate with high diastereoselectivity. The TBS-protected 2'-deoxyfluorosulfonimide sugar was prepared on an 80 g scale and isolated as a crystalline, bench-stable single diastereomer.

A chemoenzymatic strategy for site-selective functionalization of native peptides and proteins.

The emergence of new therapeutic modalities requires complementary tools for their efficient syntheses. Availability of methodologies for site-selective modification of biomolecules remains a long-standing challenge, given the inherent complexity and the presence of repeating residues that bear functional groups with similar reactivity profiles. We describe a bioconjugation strategy for modification of native peptides relying on high site selectivity conveyed by enzymes.

Diverse Catalytic Reactions for the Stereoselective Synthesis of Cyclic Dinucleotide MK-1454.

As practitioners of organic chemistry strive to deliver efficient syntheses of the most complex natural products and drug candidates, further innovations in synthetic strategies are required to facilitate their efficient construction. These aspirational breakthroughs often go hand-in-hand with considerable reductions in cost and environmental impact. Enzyme-catalyzed reactions have become an impressive and necessary tool that offers benefits such as increased selectivity and waste limitation.

Self-compassion mediates the link between attachment security and intimate relationship quality for couples navigating pregnancy.

Millions of couples navigate the transition from pregnancy to postpartum in a given year, and this period of change and adjustment in the family is associated with elevated risk for intimate relationship dysfunction. Self-compassion has the potential to promote skills that are essential for healthy adaptation (e.g.

Feasibility, effectiveness and patient satisfaction of telerehabilitation after thumb carpometacarpal arthroplasty and reverse total shoulder arthroplasty: A pilot study.

Introduction: Telemedicine is an effective, emerging interface to connect practitioners with patients. It facilitates access to healthcare expertise, reduces costs, time demands and health disparities while improving satisfaction. This pilot study evaluated the feasibility, effectiveness and patient satisfaction of telerehabilitation for thumb carpometacarpal (CMC) arthroplasty and reverse shoulder arthroplasty (rTSA).

Synthesis of a CGRP Receptor Antagonist via an Asymmetric Synthesis of 3-Fluoro-4-aminopiperidine.

A practical and efficient enantioselective synthesis of the calcitonin gene-related peptide receptor antagonist 1 has been developed. The key structural component of the active pharmaceutical ingredient is a syn-1,2-amino-fluoropiperidine 4. Two approaches were developed to synthesize this important pharmacophore.

Rheological Properties, Dissolution Kinetics, and Ocular Pharmacokinetics of Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38.

To evaluate rheological properties, dissolution, and ocular pharmacokinetics of loteprednol etabonate (LE) (submicron) ophthalmic gel 0.38%. The viscosity of the LE gel 0.

Pd-Catalyzed Synthesis of Aryl and Heteroaryl Triflones from Reactions of Sodium Triflinate with Aryl (Heteroaryl) Triflates.

A novel method for Pd-catalyzed triflination of aryl and heteroaryl triflates using NaSO2CF3 as the nucleophile is described. The combination of Pd2(dba)3 and RockPhos formed the most effective catalyst. A broad range of functional groups and heteroaromatic compounds were tolerated under the neutral reaction conditions.

Rh(I)-Catalyzed Cycloisomerization of 1,6-Enynes.

A new and unexpected Rh(I)-catalyzed cycloisomerization of 1,6-enynes is reported. Several different alkyne substitution patterns were evaluated under the reaction conditions, including a deuterated derivative that provides some insight into the reaction mechanism.

Synthesis of ent-ketorfanol via a C-H alkenylation/torquoselective 6π electrocyclization cascade.

The asymmetric synthesis of ent-ketorfanol from simple and commercially available precursors is reported. A Rh(I) -catalyzed intramolecular CH alkenylation/torquoselective 6π electrocyclization cascade provides a fused bicyclic 1,2-dihydropyridine as a key intermediate. Computational studies were performed to understand the high torquoselectivity of the key 6π electrocyclization.

Catalytic dynamic kinetic resolutions with N-heterocyclic carbenes: asymmetric synthesis of highly substituted β-lactones.

New DKR type: An N-heterocyclic carbene (NHC)-catalyzed dynamic kinetic resolution of racemic α-substituted β-keto esters has been developed. This method relies on the epimerization of an NHC-enol intermediate before subsequent aldol/acylation events. Highly substituted β-lactones are produced in good yield with good to excellent selectivities (see scheme).

Single-molecule surface-enhanced Raman spectroscopy of crystal violet isotopologues: theory and experiment.

Single-molecule surface-enhanced Raman spectroscopy (SMSERS) of crystal violet (CV) has been reported since 1997, yet others have offered alternative explanations that do not necessarily imply SMSERS. Recently, the isotopologue approach, a statistically significant method to establish SMSERS, has been implemented for members of the rhodamine dye family. We provide the first demonstration of SMSERS of a triphenylmethane dye using the isotopologue approach.

Determination of multiresidue pesticides in green tea by using a modified QuEChERS extraction and ion-trap gas chromatography/mass spectrometry.

The pesticide residues in exported and imported tea products must not exceed the maximum residue limits (MRLs) regulated by the import countries. Tea is a complex matrix that obfuscates the determination of pesticide residues. Many available methods for multiresidue pesticide analysis of tea are time-consuming and require many cleanup steps.

N-heterocyclic carbene-catalyzed conjugate additions of alcohols.

An efficient intermolecular conjugate addition of alcohols to activated alkenes catalyzed by N-heterocyclic carbenes has been developed. With 5 mol % of the free carbene derived from IMes·HCl, unsaturated ketones and esters are competent substrates, and a variety of primary and secondary alcohols can be employed as the nucleophile. No oligomerization is observed under these mild conditions for effective hydroalkoxylation.

Catalytic enantioselective total syntheses of bakkenolides I, J, and S: application of a carbene-catalyzed desymmetrization.

A general strategy for the catalytic asymmetric syntheses of the bakkenolides is reported. The key bond-forming step involves an N-heterocyclic carbene catalyzed desymmetrization of a 1,3-diketone to form three new bonds in one step with excellent enantio- and diastereoselectivity. This intramolecular reaction allows direct access to the hydrindane core of the bakkenolide family and enables a facile synthesis of these natural products.

N-Heterocyclic Carbene-Catalyzed Oxidations.

N-Heterocyclic carbenes catalyze the oxidation of allylic and benzylic alcohols as well as saturated aldehydes to esters with manganese(IV) oxide in excellent yields. A variety of esters can be synthesized, including protected carboxylates. The oxidation proceeds under mild conditions, with low loadings of a simple triazolium salt pre-catalyst in the presence of base.