First and second-order properties of charge-localized and Frost-localized orbitals

Two methods of localization of Frost-model molecular orbitals are considered, both of which are extremely easy to apply, requiring the evaluation of only one-election integrals. The chargelocalization criterion can be used with any single-determinant wavefunction, but when applied to the Frost model it yields similar orbitals to those got by orthonormalizing the basis of floating spherical gaussians, while maintaining their localized feature. Properties of charge-localized orbitals are calculated for NH₃, H₂O, CH₄, C₂H₆.     

Synthesis and purification of a metallic nitride fullerene bisadduct: exploring the reactivity of Gd3N@C80

This research represents initial functionalization of a Gd3N@C80 metallic nitride fullerene (MNF). Results demonstrate that a bisadduct can be prepared in an isolable yield for this MRI precursor MNF. This Gd3N@C80 bisadduct is synthesized and purified, and preliminary characterization is reported. This is a significant finding as, to date, only MNF monoadducts have been purified.     

Type II Anion Relay Chemistry: Exploiting Bifunctional Weinreb Amide Linchpins for the One‐Pot Synthesis of Differentiated 1,3‐Diketones,Pyrans, and Spiroketals

The design, synthesis, and validation of new highly effective bifunctional linchpins for type II anion relay chemistry (ARC) has been achieved. The mechanistically novel negative‐charge migration that comprises the Brook rearrangement is now initiated by a stabilized tetrahedral intermediate, which is generated by nucleophilic addition to a Weinreb amide, rather than by a simple oxyanion that is generated from an epoxide. As a result, the linchpin preserves the carbonyl functionality in the ARC adducts, thus permitting access to functionally complex systems in a single flask without the need for further chemical manipulations. This tactic was validated with the one‐pot preparation of monoprotected 1,3‐diketones as well as pyran and spiroketal scaffolds, depending on the choice of nucleophile, electrophile, and work‐up conditions.     

A mechanistic study on the oxidation of hydrazides: application to the tuberculosis drug isoniazid

Herein we report radical trapping experiments that support the formation of an acyl radical as the active species from the oxidation of isoniazid; these data provide insight into the mechanism of hydrazide oxidation.     

Molecular docking of cathepsin L inhibitors in the binding site of papain

The papain/CLIK-148 coordinate system was employed as a model to study the interactions of a nonpeptide thiocarbazate inhibitor of cathepsin L ( 1). This small molecule inhibitor, a thiol ester containing a diacyl hydrazine functionality and one stereogenic center, was most active as the S-enantiomer, with an IC 50 of 56 nM; the R-enantiomer ( 2) displayed only weak activity (33 microM). Correspondingly, molecular docking studies with Extra Precision Glide revealed a correlation between score and biological activity for the two thiocarbazate enantiomers when a structural water was preserved. The molecular interactions between 1 and papain were very similar to the interactions observed for CLIK-148 ( 3a and 3b) with papain, especially with regard to the hydrogen-bonding and lipophilic interactions of the ligands with conserved residues in the catalytic binding site. Subsequent docking of virtual compounds in the binding site led to the identification of a more potent inhibitor ( 5), with an IC 50 of 7.0 nM. These docking studies revealed that favorable energy scores and correspondingly favorable biological activities could be realized when the virtual compound design included occupation of the S2, S3, and S1' subsites by hydrophobic and aromatic functionalities of the ligand, and at least three hydrogen bonding contacts between the ligand and the conserved binding site residues of the protein.     

Exploring Photoredox-Catalyzed (Re)functionalizations with Core-Modified Benziodoxolones

Alkynes and nitriles are valuable building blocks in organic synthesis and also have multiple applications in chemical biology and materials science. Due to the high availability of tertiary alcohols, developing methods for their conversion into alkynes and nitriles is particularly attractive. In a previous communication, our group has reported the conversion of alcohols into alkynes through cesium oxalates based on the powerful combination of photochemistry with Ethynyl BenziodoXolones (EBXs). Herein, we report further investigations into this transformation, including our findings on the effect that backbone modification of EBXs has on the deoxyalkynylation of cesium oxalates. In addition, we disclose preliminary data on the development of new deoxycyanation and dethioalkynylation processes. We also report the serendipitous discovery of the C−H alkynylation of 1,2-dichloroethane.     

(+)-Phorboxazole A synthetic studies. Identification of a series of highly cytotoxic C(45-46) analogues

[structure: see text] Effective, scalable total syntheses and biological evaluation of six phorboxazole A analogues (1-6) have been achieved. Importantly, the C(45-46)-saturated, C(45-46)-alkenyl, and the C(45-46)-E-chloroalkenyl congeners (4, 5, and 6, respectively) reveal low nanomolar tumor cell growth inhibitory activity (GI50's) similar to or, in some cell lines, greater than that of the phorboxazoles across a diverse panel of human cancer cell lines.     

Diversity-oriented synthesis of polyketide natural products via iterative chemo- and stereoselective functionalization of polyenoates: development of a unified approach for the C(1-19) segments of lituarines A-C

A unified, stereocontrolled synthesis of the C(1-19) segments of the lituarines A-C (1-3) has been achieved, highlighted by application of an iterative chemo- and stereoselective trienoate functionalization protocol, a strategy that holds considerable promise for the diversity oriented synthesis of polyketides.     

A class of time-machine solutions with a compact vacuum core

We present a class of curved-spacetime vacuum solutions which develop closed timelike curves at some particular moment. We then use these vacuum solutions to construct a time-machine model. The causality violation occurs inside an empty torus, which constitutes the time-machine core. The matter field surrounding this empty torus satisfies the weak, dominant, and strong energy conditions. The model is regular, asymptotically flat, and topologically trivial. Stability remains the main open question.     

Extended Hückel calculations of the ionization potentials of some conjugated hydrocarbons

The prediction of ionization potentials of conjugated hydrocarbons using extended Hückel theory is reevaluated. Consequently, two major modifications to the theory are proposed and then tested on five sample molecules. Allowance for distinct sigma and pi orbital parameters as well as for diagonal and off-diagonal parameters constitute the changes examined and are shown to arise naturally from the theory. Subsequent testing of the reproduction of photoelectron spectra indicates significant improvements over previous usage of extended Hückel theory.