Editorial

Editoria

MCPB.py: A Python Based Metal Center Parameter Builder

MCPB.py, a python based metal center parameter builder, has been developed to build force fields for the simulation of metal complexes employing the bonded model approach. It has an optimized code structure, with far fewer required steps than the previous developed MCPB program. It supports various AMBER force fields and more than 80 metal ions. A series of parametrization schemes to derive force constants and charge parameters are available within the program. We give two examples (one metalloprotein example and one organometallic compound example), indicating the program’s ability to build reliable force fields for different metal ion containing complexes. The original version was released with AmberTools15. It is provided via the GNU General Public License v3.0 (GNU_GPL_v3) agreement and is free to download and distribute. MCPB.py provides a bridge between quantum mechanical calculations and molecular dynamics simulation software packages thereby enabling the modeling of metal ion centers. It offers an entry into simulating metal ions in a number of situations by providing an efficient way for researchers to handle the vagaries and difficulties associated with metal ion modeling

Taking into Account the Ion-Induced Dipole Interaction in the Nonbonded Model of Ions

Metal ions exist in almost half of the proteins in the protein databank, and they serve as structural, electron-transfer, and catalytic elements in the metabolic processes of organisms. Molecular dynamics (MD) simulation is a powerful tool that provides information about biomolecular systems at the atomic level. Coupled with the growth in computing power, algorithms like the particle mesh Ewald (PME) method have become the accepted standard when dealing with long-range interactions in MD simulations. The nonbonded model of metal ions consists of an electrostatic plus 12–6 Lennard-Jones (LJ) potential and is used largely because of its speed relative to more accurate models. In previous work we found that ideal parameters do not exist that reproduce several experimental properties for M­(II) ions simultaneously using the nonbonded model coupled with the PME method due to the underestimation of metal ion-ligand interactions. Via a consideration of the nature of the nonbonded model, we proposed that the observed error largely arises from overlooking charge-induced dipole interactions. The electrostatic plus 12–6 LJ potential model works reasonably well for neutral systems but does struggle with more highly charged systems. In the present work we designed and parametrized a new nonbonded model for metal ions by adding a 1/<i>r</i>⁴ term to the 12–6 model. We call it the 12–6–4 LJ-type nonbonded model due to its mathematical construction. Parameters were determined for 16 +2 metal ions for the TIP3P, SPC/E, and TIP4P_EW water models. The final parameters reproduce the experimental hydration free energies (HFE), ion-oxygen distances (IOD) in the first solvation shell, and coordination numbers (CN) accurately for most of the metal ions investigated. Preliminary tests on MgCl₂ at different concentrations in aqueous solution and Mg²⁺–nucleic acid systems show reasonable results suggesting that the present parameters can work in mixed systems. The 12–6–4 LJ-type nonbonded model is readily adopted into standard force fields like AMBER, CHARMM, and OPLS-AA with only a modest computational overhead. The new nonbonded model does not consider charge-transfer effects explicitly and, hence, may not be suitable for the simulation of systems where charge-transfer effects play a decisive role

Organocatalytic Enantioselective [1 + 4] Annulation of Morita–Baylis–Hillman Carbonates with Electron-Deficient Olefins: Access to Chiral 2,3-Dihydrofuran Derivatives

A reaction has been developed for the chiral phosphine-catalyzed enantioselective [1 + 4] annulation of Morita–Baylis–Hillman carbonates with electron-deficient olefins via a Michael alkylation process. Morita–Baylis–Hillman carbonates reacted smoothly with β,γ-unsaturated α-keto ester and α,β-unsaturated ketone substrates under 1,2-bis­[(2<i>R</i>,5<i>R</i>)-2,5-dimethylphospholano]­benzene monoxide catalysis to furnish a wide range of optically active 2,3-dihydrofurans in high yields (up to 95%) with excellent asymmetric induction (up to >99% ee, >20:1 dr). This protocol represents an efficient strategy for the synthesis of optically active multifunctional 2,3-dihydrofurans via an asymmetric Michael alkylation domino reaction

Double N,B-Type Bidentate Boryl Ligands Enabling a Highly Active Iridium Catalyst for C–H Borylation

Boryl ligands hold promise in catalysis due to their very high electron-donating property. In this communication double N,B-type boryl anions were designed as bidentate ligands to promote an sp² C–H borylation reaction. A symmetric pyridine-containing tetraamino­diborane(4) compound (<b>1</b>) was readily prepared as the ligand precursor that could be used, in combination with [Ir­(OMe)­(COD)]₂, to <i>in situ</i> generate a highly active catalyst for a broad range of (hetero)­arene substrates including highly electron-rich and/or sterically hindered ones. This work provides the first example of a bidentate boryl ligand in supporting homogeneous organometallic catalysis

3‑Center-5-Electron Boryl Radicals with σ⁰π¹ Ground State Electronic Structure

Five- and six-membered boron heterocycle-based three-center-five-electron (<b>3c</b>–<b>5e</b>) type boryl radicals with unusual σ⁰π¹ ground state electronic structures are predicted theoretically. Compared to σ¹π⁰ analogs, their unique electronic structure leads to both lower reactivity toward H-atoms and stronger coordination with Lewis bases. The corresponding Lewis base-stabilized four-center-seven-electron (<b>4c</b>–<b>7e</b>) type boryl radicals are even more unreactive toward H-atoms than the conventional <b>4c</b>–<b>7e</b> ones

Stereocontrolled Construction of the Tricyclic Framework of Tiglianes and Daphnanes by an Oxidative Dearomatization Approach

An appropriately functionalized [5–7–6] tricyclic framework of tigliane and daphnane diterpenes containing seven contiguous stereocenters has been prepared in 10 steps from very simple building blocks in a modular and stereocontrolled fashion. The key features of this approach involve an efficient visible light-induced singlet oxygen oxidative dearomatization and an array of substrate-controlled highly diastereoselective transformations. This work provides a model strategy for rapid and diverted synthesis of natural and unnatural molecules sharing the common skeleton

Copper-Catalyzed Boron-Selective C(sp²)–C(sp³) Oxidative Cross-Coupling of Arylboronic Acids and Alkyltrifluoroborates Involving a Single-Electron Transmetalation Process

A rapid and highly selective oxidative cross-coupling reaction between readily available and shelf-stable arylboronic acids and primary or secondary potassium alkyltrifluoroborates was devised and developed, which works under mild conditions using copper­(II) acetate as the catalyst and silver oxide as the oxidant. Initial experimental results indicate that a single-electron transmetalation process is involved. This approach effectively bypasses the problems associated with the traditional cross-coupling reactions of alkylboronates and thus provides a complementary method in building C­(sp²)–C­(sp³) bonds

Decarboxylative Borylation of Aliphatic Esters under Visible-Light Photoredox Conditions

The conventional methods for preparing alkyl boronates often necessitate anhydrous and demanding reaction conditions. Herein, a new, operationally simple decarboxylative borylation reaction of readily available aliphatic acid derivatives under additive-free visible-light photoredox conditions in nonanhydrous solvents has been described. Primary and secondary alkyl boronates or tetrafluoroborates with various functional groups were prepared accordingly. A catalytic cycle involving alkyl radical reaction with base-activated diboron species has been proposed

Using Ligand-Induced Protein Chemical Shift Perturbations To Determine Protein–Ligand Structures

Protein chemical shift perturbations (CSPs), upon ligand binding, can be used to refine the structure of a protein–ligand complex by comparing experimental CSPs with calculated CSPs for any given set of structural coordinates. Herein, we describe a fast and accurate methodology that opens up new opportunities for improving the quality of protein–ligand complexes using nuclear magnetic resonance (NMR)-based approaches by focusing on the effect of the ligand on the protein. The new computational approach, ¹H empirical chemical shift perturbation (HECSP), has been developed to rapidly calculate ligand binding-induced ¹H CSPs in a protein. Given the dearth of experimental information by which a model could be derived, we employed high-quality density functional theory (DFT) computations using the automated fragmentation quantum mechanics/molecular mechanics approach to derive a database of ligand-induced CSPs on a series of protein–ligand complexes. Overall, the empirical HECSP model yielded correlation coefficients between its predicted and DFT-computed values of 0.897 (¹HA), 0.971 (¹HN), and 0.945 (side chain ¹H) with root-mean-square errors of 0.151 (¹HA), 0.199 (¹HN), and 0.257 ppm (side chain ¹H), respectively. Using the HECSP model, we developed a scoring function (NMRScore_P). We describe two applications of NMRScore_P on two complex systems and demonstrate that the method can distinguish native ligand poses from decoys and refine protein–ligand complex structures. We provide further refined models for both complexes, which satisfy the observed ¹H CSPs in experiments. In conclusion, HECSP coupled with NMRScore_P provides an accurate and rapid platform by which protein–ligand complexes can be refined using NMR-derived information