Multiscale Responsive Kinetic Modeling: Quantifying Biomolecular Reaction Flux under Varying Electrochemical Conditions.

Attaining a complete thermodynamic and kinetic characterization for processes involving multiple interconnected rare-event transitions remains a central challenge in molecular biophysics. This challenge is amplified when the process must be understood under a range of reaction conditions. Herein, we present a novel condition-responsive kinetic modeling framework that can combine the strengths of bottom-up rate quantification from multiscale simulations with top-down solution refinement using both equilibrium and nonequilibrium experimental data.

Nernst equilibrium, rectification, and saturation: Insights into ion channel behavior.

The dissipation of electrochemical gradients through ion channels plays a central role in biology. Herein we use voltage-responsive kinetic models of ion channels to explore how electrical and chemical potentials differentially influence ion transport properties. These models demonstrate how electrically driven flux is greater than the Nernstian equivalent chemically driven flux yet still perfectly cancels when the two gradients oppose each other.

Multiscale Responsive Kinetic Modeling: Quantifying Biomolecular Reaction Flux under Varying Electrochemical Conditions.

Attaining a complete thermodynamic and kinetic characterization for processes involving multiple interconnected rare-event transitions remains a central challenge in molecular biophysics. This challenge is amplified when the process must be understood under a range of reaction conditions. Herein, we present a condition-responsive kinetic modeling framework that can combine the strengths of bottom-up rate quantification from multiscale simulations with top-down solution refinement using experimental data.

Machine learning classification of disrotatory IRC and conrotatory non-IRC trajectory motion for cyclopropyl radical ring opening.

Quasiclassical trajectory analysis is now a standard tool to analyze non-minimum energy pathway motion of organic reactions. However, due to the large amount of information associated with trajectories, quantitative analysis of the dynamic origin of reaction selectivity is complex. For the electrocyclic ring opening of cyclopropyl radical, more than 4000 trajectories were run showing that allyl radicals are formed through a mixture of disrotatory intrinsic reaction coordinate (IRC) motion as well as conrotatory non-IRC motion.

Mechanistic molecular motion of transition-metal mediated β-hydrogen transfer: quasiclassical trajectories reveal dynamically ballistic, dynamically unrelaxed, two step, and concerted mechanisms.

The transfer of a β-hydrogen from a metal-alkyl group to ethylene is a fundamental organometallic transformation. Previously proposed mechanisms for this transformation involve either a two-step β-hydrogen elimination and migratory insertion sequence with a metal hydride intermediate or a one-step concerted pathway. Here, we report density functional theory (DFT) quasiclassical direct dynamics trajectories that reveal new dynamical mechanisms for the β-hydrogen transfer of [Cp*RhIII(Et)(ethylene)]+.

Machine Learning Analysis of Direct Dynamics Trajectory Outcomes for Thermal Deazetization of 2,3-Diazabicyclo[2.2.1]hept-2-ene.

Experimentally, the thermal gas-phase deazetization of 2,3-diazabicyclo[2.2.1]hept-2-ene () results in the loss of N and the formation of bicyclo products (exo) and (endo) in a nonstatistical ratio, with preference for the exo product.

Direct dynamics analysis of the cationic Cp*(PMe)Ir(CH) methane C-H activation mechanism.

For the σ-bond metathesis reaction between methane and cationic Cp*(PMe3)IrIII(CH3), previous static DFT calculations revealed a two-step oxidative addition/reductive elimination mechanism with an intervening IrV-H intermediate. We recently reported quasiclassical direct molecular dynamics simulations where starting from the vibrationally-averaged oxidative addition transition state a minor, but significant, amount of trajectories bypassed the IrV-H intermediate in a dynamical one-step mechanism. These trajectories also revealed that after the reductive coupling transition state is passed methane always dissociates and the C-H σ-complex is skipped.

Dynamical Mechanism May Avoid High-Oxidation State Ir(V)-H Intermediate and Coordination Complex in Alkane and Arene C-H Activation by Cationic Ir(III) Phosphine.

Organometallic reaction mechanisms are assumed to be appropriately described by minimum energy pathways mapped out by density functional theory calculations. For the two-step oxidative addition/reductive elimination mechanism for C-H activation of methane and benzene by cationic Cp*(PMe)Ir(CH), we report quasiclassical direct dynamics simulations that demonstrate the Ir-H intermediate is bypassed in a significant amount of productive trajectories initiated from vibrationally averaged velocity distributions of oxidative addition transition states. This organometallic dynamical mechanism is akin to the σ-bond metathesis pathway but occurs on the oxidative addition/reductive elimination energy surface and blurs the line between two- and one-step mechanisms.

Allylic amination reactivity of Ni, Pd, and Pt heterobimetallic and monometallic complexes.

Transition metal heterobimetallic complexes with dative metal-metal interactions have the potential for novel fast reactivity. There are few studies that both compare the reactivity of different metal centers in heterobimetallic complexes and compare bimetallic reactivity to monometallic reactivity. Here we report density-functional calculations that show the reactivity of [Cl2Ti(N(t)BuPPh2)2M(II)(η(3)-methallyl)] heterobimetallic complexes for allylic amination follows M = Ni > Pd > Pt.