Donor Ability of Bisphosphinemonoxide Ligands Relevant to Late-Metal Olefin Polymerization Catalysis.

Late-transition-metal catalysts for polymerization of olefins have drawn a significant amount of attention owing to their ability to tolerate and incorporate polar comonomers. However, a systematic way to experimentally quantify the electronic properties of the ligands used in these systems has not been developed. Quantified ligand parameters will allow for the rational design of tailored polymerization catalysts, which would target specific polymer properties. We report a series of platinum complexes bearing bisphosphinemonoxide ligands, which resemble those used in the polymerization catalysts of Nozaki and Chen. Their electronic properties are investigated experimentally, and trends are rationalized by using computed spectral properties. Benchmarking computational data with known experimental parameters further enhances the utility of both methods for determining optimal ligands for catalytic application.

The influence of model building schemes and molecular dynamics sampling on QM-cluster models: the chorismate mutase case study.

Most QM-cluster models of enzymes are constructed based on X-ray crystal structures, which limits comparison to in vivo structure and mechanism. The active site of chorismate mutase from Bacillus subtilis and the enzymatic transformation of chorismate to prephenate is used as a case study to guide construction of QM-cluster models built first from the X-ray crystal structure, then from molecular dynamics (MD) simulation snapshots. The Residue Interaction Network ResidUe Selector (RINRUS) software toolkit, developed by our group to simplify and automate the construction of QM-cluster models, is expanded to handle MD to QM-cluster model workflows. Several options, some employing novel topological clustering from residue interaction network (RIN) information, are evaluated for generating conformational clustering from MD simulation. RINRUS then generates a statistical thermodynamic framework for QM-cluster modeling of the chorismate mutase mechanism via refining 250 MD frames with density functional theory (DFT). The 250 QM-cluster models sampled provide a mean ΔG‡ of 10.3 ± 2.6 kcal mol-1 compared to the experimental value of 15.4 kcal mol-1 at 25 °C. While the difference between theory and experiment is consequential, the level of theory used is modest and therefore "chemical" accuracy is unexpected. More important are the comparisons made between QM-cluster models designed from the X-ray crystal structure versus those from MD frames. The large variations in kinetic and thermodynamic properties arise from geometric changes in the ensemble of QM-cluster models, rather from the composition of the QM-cluster models or from the active site-solvent interface. The findings open the way for further quantitative and reproducible calibration in the field of computational enzymology using the model construction framework afforded with the RINRUS software toolkit.

Neutral gas pressure dependence of ion-ion mutual neutralization rate constants using Landau-Zener theory coupled with trajectory simulations.

In this computational study, we describe a self-consistent trajectory simulation approach to capture the effect of neutral gas pressure on ion-ion mutual neutralization (MN) reactions. The electron transfer probability estimated using Landau-Zener (LZ) transition state theory is incorporated into classical trajectory simulations to elicit predictions of MN cross sections in vacuum and rate constants at finite neutral gas pressures. Electronic structure calculations with multireference configuration interaction and large correlation consistent basis sets are used to derive inputs to the LZ theory. The key advance of our trajectory simulation approach is the inclusion of the effect of ion-neutral interactions on MN using a Langevin representation of the effect of background gas on ion transport. For H+ - H- and Li+ - H(D)-, our approach quantitatively agrees with measured speed-dependent cross sections for up to ∼105 m/s. For the ion pair Ne+ - Cl-, our predictions of the MN rate constant at ∼1 Torr are a factor of ∼2 to 3 higher than the experimentally measured value. Similarly, for Xe+ - F- in the pressure range of ∼20 000-80 000 Pa, our predictions of the MN rate constant are ∼20% lower but are in excellent qualitative agreement with experimental data. The paradigm of using trajectory simulations to self-consistently capture the effect of gas pressure on MN reactions advanced here provides avenues for the inclusion of additional nonclassical effects in future work.

Evaluating the active site-substrate interplay between x-ray crystal structure and molecular dynamics in chorismate mutase.

Designing realistic quantum mechanical (QM) models of enzymes is dependent on reliably discerning and modeling residues, solvents, and cofactors important in crafting the active site microenvironment. Interatomic van der Waals contacts have previously demonstrated usefulness toward designing QM-models, but their measured values (and subsequent residue importance rankings) are expected to be influenceable by subtle changes in protein structure. Using chorismate mutase as a case study, this work examines the differences in ligand-residue interatomic contacts between an x-ray crystal structure and structures from a molecular dynamics simulation. Select structures are further analyzed using symmetry adapted perturbation theory to compute ab initio ligand-residue interaction energies. The findings of this study show that ligand-residue interatomic contacts measured for an x-ray crystal structure are not predictive of active site contacts from a sampling of molecular dynamics frames. In addition, the variability in interatomic contacts among structures is not correlated with variability in interaction energies. However, the results spotlight using interaction energies to characterize and rank residue importance in future computational enzymology workflows.

Rovibrational Quantum Chemical Treatment of Inorganic and Organometallic Astrochemicals.

ConspectusOur two groups have both independently and collaboratively been pushing quantum-chemical techniques to produce highly accurate predictions of anharmonic vibrational frequencies and spectroscopic constants for molecules containing atoms outside of the typical upper p block. Methodologies employ composite approaches, relying on various levels of coupled cluster theory-most often at the singles, doubles, and perturbative triples level-and quartic force field constructions of the potential portion of the intramolecular Watson Hamiltonian. Such methods are known to perform well for organic species, and we have extended this to molecules containing atoms outside of this realm.One notable atom that has received much attention in this application is magnesium. Mg is the second-most-abundant element in the Earth's mantle, and while molecules containing this element are among the confirmed astrochemicals, its further atomic abundance in the galaxy implies that many more molecules (both purely inorganic and organometallic) containing element 12 exist in astrophysical regions in chemical sizes between those of atoms and dust-sized nanocrystals. Our approach discussed herein is producing quality benchmarks and predicting novel data for magnesium-bearing molecules.The story is similar for Al and Si, which are also notably abundant in both rocky bodies and the universe at large. While Na, Sc, and Cu may not be as abundant as Mg, Al, and Si, molecules containing Na and transition metals have also previously been reported to be detected beyond the Earth. Consequently, the need to produce spectral reference data for molecules containing such atoms is growing. While several experimental groups (including, notably, the groups in Arizona, Boston, and France/Spain) have clearly led the way in detection of inorganic/organometallic molecules in space, computational support and even rational design can provide novel avenues for the detection of molecules containing atoms not typically studied in most laboratories. The application of quantum chemistry to other elements beyond carbon and its cronies at the top right of the periodic table promises a better understanding of the observable universe. It will also provide novel and fundamental chemical insights pushing the "central science" into new molecular territory.

Theoretical Rovibrational Spectroscopy of Magnesium Tricarbide-Multireference Character Thwarts a Full Analysis of All Isomers.

Magnesium tricarbide isomers are studied herein with coupled cluster theory and multireference configuration interaction to support their possible detection in astrochemical environments such as the circumstellar envelope surrounding the star IRC +10216 or in terrestrial laboratories. Magnesium-bearing species may abound in the interstellar medium (ISM), but only eight (MgNC, MgCN, HMgNC, MgC2H, MgC3N, MgC4H, MgC5N, and MgC6H) have been directly identified thus far. Several possible isomers for the related MgC3 system are explored in their singlet and triplet spin multiplicities. Overall, this work offers quantum chemical insight of rovibrational spectroscopic data for MgC3 using quartic force fields (QFFs) based on the CCSD(T) and CCSD(T)-F12 levels of theory at the complete basis set (CBS) limit. Additional corrections with small basis set CCSDT(Q) and scalar relativistic effects are also included in the analysis. Salient multireference character is found in the singlet diamond electronic state, which makes a definitive assignment of the ground state challenging. Nevertheless, coupled cluster-based composite energies and multireference configuration interaction both predict that the 1A1 diamond isomer is 1.6-2.2 kcal mol-1 lower in energy than the 3A1 diamond isomer. Furthermore, highly accurate binding energies of various isomers MgC3 are provided for comparison to photodetachment experiments. Dipole moments along with harmonic infrared intensities will guide efforts for astronomical and spectroscopic characterization.

Cheminformatic quantum mechanical enzyme model design: A catechol-O-methyltransferase case study.

To accurately simulate the inner workings of an enzyme active site with quantum mechanics (QM), not only must the reactive species be included in the model but also important surrounding residues, solvent, or coenzymes involved in crafting the microenvironment. Our lab has been developing the Residue Interaction Network Residue Selector (RINRUS) toolkit to utilize interatomic contact network information for automated, rational residue selection and QM-cluster model generation. Starting from an x-ray crystal structure of catechol-O-methyltransferase, RINRUS was used to construct a series of QM-cluster models. The reactant, product, and transition state of the methyl transfer reaction were computed for a total of 550 models, and the resulting free energies of activation and reaction were used to evaluate model convergence. RINRUS-designed models with only 200-300 atoms are shown to converge. RINRUS will serve as a cornerstone for improved and automated cheminformatics-based enzyme model design.

Acylation and deacylation mechanism and kinetics of penicillin G reaction with Streptomyces R61 DD-peptidase.

Two quantum mechanical (QM)-cluster models are built for studying the acylation and deacylation mechanism and kinetics of Streptomyces R61 DD-peptidase with the penicillin G at atomic level detail. DD-peptidases are bacterial enzymes involved in the cross-linking of peptidoglycan to form the cell wall, necessary for bacterial survival. The cross-linking can be inhibited by antibiotic beta-lactam derivatives through acylation, preventing the acyl-enzyme complex from undergoing further deacylation. The deacylation step was predicted to be rate-limiting. Transition state and intermediate structures are found using density functional theory in this study, and thermodynamic and kinetic properties of the proposed mechanism are evaluated. The acyl-enzyme complex is found lying in a deep thermodynamic sink, and deacylation is indeed the severely rate-limiting step, leading to suicide inhibition of the peptidoglycan cross-linking. The usage of QM-cluster models is a promising technique to understand, improve, and design antibiotics to disrupt function of the Streptomyces R61 DD-peptidase.

CO2 Capture by 2-(Methylamino)pyridine Ligated Aluminum Alkyl Complexes.

A set of novel, easily synthesized aluminum complexes, Al[κ2-N,N-2-(methylamino)pyridine]2R (R = Et, iBu) are reported. When subjected to 1 atm of CO2 pressure, each hemilabile pyridine arm dissociates and facilitates cooperative activation of the CO2 substrate reminiscent of a Frustrated Lewis Pair. This reaction has limited precedent for Al/N based Lewis Pair systems, and this is the first system readily shown to sequester multiple equivalents of CO2 per aluminum center. The ethyl variant then reacts further, inserting a third equivalent of CO2 into the aluminum alkyl to generate an aluminum carboxylate. Examples of this type of reactivity are rare under thermal conditions. A joint experimental/computational study supports the proposed reaction mechanism.

Hydrogen Activation and Hydrogenolysis Facilitated By Late-Transition-Metal-Aluminum Heterobimetallic Complexes.

Previously reported heterobimetallic rhodium-aluminum and iridium-aluminum alkyl complexes are shown to activate hydrogen, generating the corresponding alkane. Kinetic data indicate a mechanistic difference between the iridium- and rhodium-based systems. In both cases the transition metal is an active participant in the release of alkane from the aluminum center. For iridium-aluminum species, experimental mechanistic data suggest that multiple pathways occur concomitantly with each other: one being the oxidative addition of hydrogen followed by proton transfer resulting in alkane generation. Computational data indicate a reasonable barrier to formation of an iridium dihydride intermediate observed experimentally. In the case of the rhodium-aluminum species, hydrides are not observed spectroscopically, though a reasonable barrier to formation of this thermodynamically unstable species has been calculated. Alternative mechanistic possibilities are discussed and explored computationally. Cooperative hydrogenolysis mechanisms are computed to be energetically unfeasible for both metal centers.

Quantifying Inter-Residue Contacts through Interaction Energies.

The validity and accuracy of protein modeling is dependent on constructing models that account for the inter-residue interactions crucial for protein structure and function. Residue interaction networks derived from interatomic van der Waals contacts have previously demonstrated usefulness toward designing protein models, but there has not yet been evidence of a connection between network-predicted interaction strength and quantitative interaction energies. This work evaluates the intraprotein contact networks of five proteins against ab initio interaction energies computed using symmetry-adapted perturbation theory. To more appropriately capture the local chemistry of the protein, we deviate from traditional protein network analysis to redefine the interacting nodes in terms of main chain and side chain functional groups rather than complete amino acids. While there is no simple correspondence between the features of the contact network and actual interaction strength, random forest models constructed from minimal structural, network, and chemical descriptors are capable of accurately predicting interaction energy. The results of this work serve as a foundation for the development and improvement of functional group-based contact networks.

On the formation of phosphorous polycyclic aromatics hydrocarbons (PAPHs) in astrophysical environments.

The formation of phosphorous-containing polycyclic aromatic hydrocarbons (PAPHs) in astrophysical contexts is proposed and analyzed by means of computational methods [B3LYP-D3BJ/ma-def2-TZVPP, MP2-F12, CCSD-F12b and CCSD(T)-F12b levels of theory]. A "bottom-up" approach based on a radical-neutral reaction scheme between acetylene (C2H2) and the CP radical was used investigating: (a) the synthesis of the first PAPH (C5H5P) "phosphinine"; (b) PAPH growth by addition of C2H2 to the C5H4P radical; (c) PAPH synthesis by addition reactions of one CP radical and nC2H2 to a neutral PAH. Results show: (I) the formation of the phosphinine radical has a strong thermodynamic tendency (-133.3 kcal mol-1) and kinetic barriers ≤5.4 kcal mol-1; (II) PAPH growth by nC2H2 addition on the radical phosphinine easily and exothermically produces radicals (1a- or 1-phospha-naphtalenes with kinetic barriers ≤7.1 kcal mol-1 and reaction free energies ≤-102.5 kcal mol-1); (III) the addition of a single CP + nC2H2 to a neutral benzene generates a complex chemistry where the main product is 2-phospha-naphtalene; (IV) because of the CP radical character, its barrierless addition to a PAH produces a resonant stabilized PAPH, becoming excellent candidates for addition reactions with neutral or radical hydrocarbons and PAHs; (V) the same energy trend between all four levels of theory continues a well-calibrated computational protocol to analyze complex organic reactions with astrochemical interest using electronic structure theory.

Theoretical study of the low-lying electronic states of iron hydride cation.

Both FeH and FeH+ are predicted to be abundant in cool stellar atmospheres and proposed to be molecular components of the gas phase interstellar medium (ISM). However, experimental and simulated data for both species are lacking, which have hindered astronomical detection. There are no published laboratory data for the spectroscopy of FeH+ in any frequency regime. It is also not established if FeH+ possesses salient multireference character, which would pose significant challenges for ab initio modeling of geometric and spectroscopic properties. With a set of high-level coupled cluster and multireference configuration interaction computations, a study of the electronic structure of the ground state and seven excited states of FeH+ was carried out. An X5Δi electronic ground state of FeH+ is found, in agreement with previous theoretical studies. Including corrections for spin-orbit coupling and anharmonic vibrational effects, the Ω = 3, ν = 0 spin ladder of the A5Πi electronic state lies 872 cm-1 higher in energy than the Ω = 4, ν = 0 spin ladder of the ground state. Combined with previous work in our laboratory, the ionization energy of FeH is computed to be 7.4851 eV. With modern multireference configuration interaction and coupled cluster methods, spectroscopic constants (re, Be, ωe, ωexe, αe, and D¯e) for several bound excited states (A5Πi, B 5Σi +, a 3Σr -, b3Φi, c3Πi, d3Δr, and 7Σ+) were characterized. This study will lead efforts to identify FeH+ in the ISM and help solve important remaining questions in quantifying metal-hydride bonding.

Synthesis and Characterization of Heterobimetallic Iridium-Aluminum and Rhodium-Aluminum Complexes.

We demonstrate the synthesis and characterization of a new class of late-transition-metal-aluminum heterobimetallic complexes via a novel synthetic pathway. Complexes of this type are exceedingly rare. Joint experimental and theoretical data sheds light on the electronic effect of ligands containing aluminum moieties on late-transition-metal complexes.

A transition state "trapped"? QM-cluster models of engineered threonyl-tRNA synthetase.

In a recent study [Science, 2015, 347, 6224], protein engineering was used to design a core within the enzyme threonyl-tRNA synthetase (ThrRS) capable of stabilizing the coplanar transition state conformation of an inserted noncanonical p-biphenylalanine (BiPhe) residue. Using the X-ray crystal structures of the preliminary (Protein Data Bank entries 4S02, 4S0J, 4S0L, 4S0I, and 4S0K) and final (PDB entry 4S03) ThrRS proteins, fully quantum mechanical (QM) cluster models were constructed and analyzed. Density functional theory and molecular dynamics computations were performed to investigate the energetic profiles of BiPhe dihedral rotation within the ThrRS models. For the 4S03 model, results indicate that steric and hydrophobic forces of the residues surrounding BiPhe eliminate the coplanar transition state entirely. Molecular dynamics simulations were carried out that confirmed the extent of BiPhe rotational flexibility, and provided additional information on barrier heights of full BiPhe rotation. Transition states of near-coplanar biphenyl rings of BiPhe were found for the 4S0I and 4S0K models, but are not likely persistent on any observable timescale. The dihedral angle of the biphenyl moiety is thermally allowed to fluctuate within the ThrRS protein core models by a range of 17°-26°. BiPhe-residue interaction counts (RICs) were used to compare the interaction differences among the different ThrRS cores. The RICs demonstrate how BiPhe is compacted within the 4S03 core, resulting in the experimentally observed "trapped" coplanar transition state analogue. This work presents a unique application of QM-cluster models towards studying the inner workings of proteins, and suggests avenues that computational chemistry can be used to further guide bioengineering.

Propylene Oxide Formation on a Silica Surface with Peroxo Defects: Implications in Astrochemistry.

The formation of the chiral molecule propylene oxide (CH3CHCH2O) recently detected in the interstellar medium (ISM) is proposed to take place on an amorphous silicate grain surface where peroxo defects are present. A computational analysis conducted at the DFT and MP2-F12 levels of theory on a neat amorphous silica model supports such a hypothesis resulting in (a) strong thermodynamic driving forces and low activation energies allowing the synthesis of CH3CHCH2O at low temperatures, (b) chemical defects on silica surfaces promoting heterogeneous catalysis of the increasing molecular complexity found in interstellar and circumstellar medium, and (c) chemical defects that have implications on understanding how processing phases modify the nature of the reactive groups on a silica surface affecting the surface catalytic activity.

Raman and Infrared Studies of Platinum-Based Drugs: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, and Heptaplatin.

This study reports the optimized structures and lowest-energy conformations/stereochemistry of five currently used platinum-based drugs: cisplatin, carboplatin, nedaplatin, oxaliplatin, and heptaplatin. Normal Raman and IR spectra of each drug are experimentally obtained and have been compared to various levels of density functional theory (DFT). Although some combination of structure, reactivity, or spectroscopy for these drugs has been studied by various groups, there are no known experimental normal Raman and IR spectra for nedaplatin, oxaliplatin, and heptaplatin in the literature. The detailed structural and vibration findings of these drugs are very important to understanding platinum behavior and drug dynamics. The following work explores the vibrational frequencies of these drugs particularly by focusing on the low-energy modes between 200 and 600 cm-1, where anharmonicity effects will have less influence on the accuracy of computed frequencies. Ideally, the Pt-N stretching modes provide vibrational diagnostics for each drug. Interestingly, a vibrational energy decomposition analysis (VEDA) suggests that oxaliplatin and heptaplatin Pt-N stretching modes are not Raman or IR active. Instead, C-C and Pt-O stretching frequencies in the various bidentate dioxo ligands might be more useful in characterizing new cisplatin derivatives. Analysis of anharmonicity effects was compared against (and in tandem with) dimer computations of four of the five drugs. Harmonic vibrational computations of the dimeric cisplatin derivatives provided greater qualitative improvement than that of the monomeric derivatives. Satisfying agreement with experimental Raman spectra was obtained, even without resorting to linear scale factors for the harmonic dimer frequencies.

Prediction of the reduction potential in transition-metal containing complexes: How expensive? For what accuracy?

Accurate computationally derived reduction potentials are important for catalyst design. In this contribution, relatively inexpensive density functional theory methods are evaluated for computing reduction potentials of a wide variety of organic, inorganic, and organometallic complexes. Astonishingly, SCRF single points on B3LYP optimized geometries with a reasonably small basis set/ECP combination works quite well--B3LYP with the BS1 [modified-LANL2DZ basis set/ECP (effective core potential) for metals, LANL2DZ(d,p) basis set/LANL2DZ ECP for heavy nonmetals (Si, P, S, Cl, and Br), and 6-31G(d') for other elements (H, C, N, O, and F)] and implicit PCM solvation models, SMD (solvation model based on density) or IEFPCM (integral equation formalism polarizable continuum model with Bondi atomic radii and α = 1.1 reaction field correction factor). The IEFPCM-Bondi-B3LYP/BS1 methodology was found to be one of the least expensive and most accurate protocols, among six different density functionals tested (BP86, PBEPBE, B3LYP, B3P86, PBE0, and M06) with thirteen different basis sets (Pople split-valence basis sets, correlation consistent basis sets, or Los Alamos National Laboratory ECP/basis sets) and four solvation models (SMD, IEFPCM, IPCM, and CPCM). The MAD (mean absolute deviation) values of SCRF-B3LYP/BS1 of 49 studied species were 0.263 V for SMD and 0.233 V for IEFPCM-Bondi; and the linear correlations had respectable R2 values (R2 = 0.94 for SMD and R2 = 0.93 for IEFPCM-Bondi). These methodologies demonstrate relatively reliable, convenient, and time-saving functional/basis set/solvation model combinations in computing the reduction potentials of transition metal complexes with moderate accuracy. © 2017 Wiley Periodicals, Inc.

Towards a quantum chemical protocol for the prediction of rovibrational spectroscopic data for transition metal molecules: Exploration of CuCN, CuOH, and CuCCH.

High accuracy electronic structure computations for small transition metal-containing molecules have been a long term challenge. Due to coupling between electronic and nuclear wave functions, even experimental/theoretical identification of the ground electronic state requires tremendous efforts. Quartic force fields (QFFs) are effective ab initio tools for obtaining reliable anharmonic spectroscopic properties. However, the method that employs complete basis set limit extrapolation ("C"), consideration of core electron correlation ("cC"), and inclusion of scalar relativity ("R") to produce the energy points on the QFF, the composite CcCR methodology, has not yet been utilized to study inorganic spectroscopy. This work takes the CcCR methodology and adapts it to test whether such an approach is conducive for the closed-shell, copper-containing molecules CuCN, CuOH, and CuCCH. Gas phase rovibrational data are provided for all three species in their ground electronic states. Equilibrium geometries and many higher-order rovibrational properties show good agreement with earlier studies. However, there are notable differences, especially in computation of fundamental vibrational frequencies. Even with further additive corrections for the inner core electron correlation and coupled cluster with full single, double, and triple substitutions (CCSDT), the differences are still larger than expected indicating that more work should follow for predicting rovibrational properties of transition metal molecules.

H2 Formation on Cosmic Grain Siliceous Surfaces Grafted with Fe+ : A Silsesquioxanes-Based Computational Model.

Cosmic siliceous dust grains are involved in the synthesis of H2 in the inter-stellar medium. In this work, the dust grain siliceous surface is represented by a hydrogen Fe-metalla-silsesquioxane model of general formula: [Fe(H7 Si7 O12-n )(OH)n ]+ (n=0,1,2) where Fe+ behaves like a single-site heterogeneous catalyst grafted on a siliceous surface synthesizing H2 from H. A computational analysis is performed using two levels of theory (B3LYP-D3BJ and MP2-F12) to quantify the thermodynamic driving force of the reaction: [Fe-T7H7 ]+ +4H→[Fe-T7H7 (OH)2 ]+ +H2 . The general outcomes are: 1) H2 synthesis is thermodynamically strongly favored; 2) Fe-H / Fe-H2 barrier-less formation potential; 3) chemisorbed H-Fe leads to facile H2 synthesis at 20≤T≤100 K; 4) relative spin energetics and thermodynamic quantities between the B3LYP-D3BJ and MP2-F12 levels of theory are in qualitative agreement. The metalla-silsesquioxane model shows how Fe+ fixed on a siliceous surface can potentially catalyze H2 formation in space.