Search

© 2019 American Chemical Society. Methyl transferases (MTases) are a well-studied class of enzymes for which competing enzymatic enhancement mechanisms have been suggested, ranging from structural methyl group CH···X hydrogen bonds (HBs) to electrostatic- and charge-transfer-driven stabilization of the transition state (TS). We identified all Class I MTases for which reasonable resolution (<2.0 Å) crystal structures could be used to form catalytically competent ternary complexes for multiscale (i.e., quantum-mechanical/molecular-mechanical or QM/MM) simulation of the SN2 methyl transfer reaction coordinate. The four Class I MTases studied have both distinct functions (e.g., protein repair or biosynthesis) and substrate nucleophiles (i.e., C, N, or O). While CH···X HBs stabilize all reactant complexes, no universal TS stabilization role is found for these interactions in MTases. A consistent picture is instead obtained through analysis of charge transfer and electrostatics, wherein much of cofactor-substrate charge separation is maintained in the TS region, and electrostatic potential is correlated with substrate nucleophilicity (i.e., intrinsic reactivity).

Indium phosphide quantum dots (QDs) represent promising replacements for more toxic QDs, but InP QD production lags behind other QD materials due to limited understanding of how to tune InP QD growth. We carry out a first-principles, computational screen of the tuning of In carboxylate precursor chemistry to alter the kinetics of elementary steps in InP QD growth. We employ a large database normally used for discovery of therapeutic drug-like molecules to discover design rules for these inorganic complexes while maintaining realism (i.e., stable, synthetically accessible substituents) and providing diversity in a 210-molecule test set. We show the In–O bond cleavage energy, which is tuned through ligand functionalization, to be a useful proxy for In–P bond formation energetics in InP QD synthesis. Energy decomposition analysis on a 32-molecule subset reveals that lower activation energies correlate to later transition states, due to stabilization from greater In–P bond formation and more favorable reaction energetics. Our simulations suggest that altering ligand nucleophilicity tunes the reaction barrier over a 10 kcal/mol range, providing the conjugate acid’s pKa as an experimental handle to lead to better control of growth conditions and to improve synthesized InP QD quality. Importantly, these trends hold regardless of phosphorus precursor chemistries and in the longer chain length ligands typically used in synthesis., National Science Foundation (Grant ECCS-1449291)

Virtual high throughput screening, typically driven by first-principles, density functional theory calculations, has emerged as a powerful tool for the discovery of new materials. Although the computational materials science community has benefited from open source tools for the rapid structure generation, calculation, and analysis of crystalline inorganic materials, software and strategies to address the unique challenges of inorganic complex discovery have not been as widely available. We present a unified view of our recent developments in the open source molSimplify code for inorganic discovery. Building on our previous efforts in the automated generation of highly accurate inorganic molecular structures, first-principles simulation, and property analysis to accelerate high-throughput screening, we have recently incorporated a neural network that both improves structure generation and predicts electronic properties prior to first-principles calculation. We also provide an overview of how multimillion molecule organic libraries can be leveraged for inorganic discovery alongside cheminformatics concepts of molecular diversity in order to efficiently traverse chemical space. We demonstrate all of these tools on the discovery of design rules for octahedral Fe(II/III) redox couples with nitrogen ligands. Over a search of only approximately 40 new molecules, we obtain redox potentials relative to the Fc/Fc+ couple ranging from −1 to 4.5 V in aqueous solution. Our new automated correlation analysis reveals heteroatom identity and the degree of structural branching to be key ligand descriptors in determining redox potential. This inorganic discovery toolkit provides a promising approach to advancing transition metal complex design., National Science Foundation (Grant ECCS-1449291)

Enzymes have evolved to facilitate challenging reactions at ambient conditions with specificity seldom matched by other catalysts. Computational modeling provides valuable insight into catalytic mechanism, and the large size of enzymes mandates multi-scale, quantum mechanical-molecular mechanical (QM/MM) simulations. Although QM/MM plays an essential role in balancing simulation cost to enable sampling with the full QM treatment needed to understand electronic structure in enzyme active sites, the relative importance of these two strategies for understanding enzyme mechanism is not well known. We explore challenges in QM/MM for studying the reactivity and stability of three diverse enzymes: i) Mg[supercript 2+]-dependent catechol O-methyltransferase (COMT), ii) radical enzyme choline trimethylamine lyase (CutC), and iii) DNA methyltransferase (DNMT1), which has structural Zn[superscript 2+] binding sites. In COMT, strong non-covalent interactions lead to long range coupling of electronic structure properties across the active site, but the more isolated nature of the metallocofactor in DNMT1 leads to faster convergence of some properties. We quantify these effects in COMT by computing covariance matrices of by-residue electronic structure properties during dynamics and along the reaction coordinate. In CutC, we observe spontaneous bond cleavage following initiation events, highlighting the importance of sampling and dynamics. We use electronic structure analysis to quantify the relative importance of CHO and OHO non-covalent interactions in imparting reactivity. These three diverse cases enable us to provide some general recommendations regarding QM/MM simulation of enzymes., NEC Corporation, National Institute of Environmental Health Sciences (Grant P30-ES002109), Burroughs Wellcome Fund (Career Award at the Scientific Interface), United States. Department of Energy (Computational Science Graduate Fellowship)

We report the observation of eigenstates that embody large-amplitude, local-bending vibrational motion in acetylene by stimulated emission pumping spectroscopy via vibrational levels of the S1 state involving excitation in the non-totally symmetric bending modes. The N[subscript b] = 14 level, lying at 8971.69 cm[superscript −1] (J = 0), is assigned on the basis of degeneracy due to dynamical symmetry breaking in the local-mode limit. The level pattern for the N[subscript b] = 16 level, lying at 10 218.9 cm[superscript−1], is consistent with expectations for increased separation of ℓ = 0 and 2 vibrational angular momentum components. Increasingly poor agreement between our observations and the predicted positions of these levels highlights the failure of currently available normal mode effective Hamiltonian models to extrapolate to regions of the potential energy surface involving large-amplitude displacement along the acetylene ⇌ vinylidene isomerization coordinate, United States. Dept. of Energy. Office of Basic Energy Sciences. Chemical Sciences Geosciences and Biosciences Division (Award No. DE-FG0287ER13671)

Chirped-pulse millimeter-wave (CPmmW) spectroscopy is the first broadband (multi-GHz in each shot) Fourier-transform technique for high-resolution survey spectroscopy in the millimeter-wave region. The design is based on chirped-pulse Fourier-transform microwave (CP-FTMW) spectroscopy [G. G. Brown, B. C. Dian, K. O. Douglass, S. M. Geyer, S. T. Shipman, and B. H. Pate, Rev. Sci. Instrum. 79, 053103 (2008)]10.1063/1.2919120, which is described for frequencies up to 20 GHz. We have built an instrument that covers the 70–102 GHz frequency region and can acquire up to 12 GHz of spectrum in a single shot. Challenges to using chirped-pulse Fourier-transform spectroscopy in the millimeter-wave region include lower achievable sample polarization, shorter Doppler dephasing times, and problems with signal phase stability. However, these challenges have been partially overcome and preliminary tests indicate a significant advantage over existing millimeter-wave spectrometers in the time required to record survey spectra. Further improvement to the sensitivity is expected as more powerful broadband millimeter-wave amplifiers become affordable. The ability to acquire broadband Fourier-transform millimeter-wave spectra enables rapid measurement of survey spectra at sufficiently high resolution to measure diagnostically important electronic properties such as electric and magnetic dipole moments and hyperfine coupling constants. It should also yield accurate relative line strengths across a broadband region. Several example spectra are presented to demonstrate initial applications of the spectrometer., United States. Dept. of Energy (Grant DEFG0287ER13671), National Science Foundation (U.S.). Graduate Research Fellowship Program

A systematic analysis of the S[subscript 1]-trans ([bar-over A][superscript 1]A[subscript u]) state of acetylene, using IR-UV double resonance along with one-photon fluorescence excitation spectra, has allowed assignment of at least part of every single vibrational state or polyad up to a vibrational energy of 4200 cm[superscript –1]. Four observed vibrational levels remain unassigned, for which no place can be found in the level structure of the trans-well. The most prominent of these lies at 46 175 cm[superscript –1]. Its [superscript 13]C isotope shift, exceptionally long radiative lifetime, unexpected rotational selection rules, and lack of significant Zeeman effect, combined with the fact that no other singlet electronic states are expected at this energy, indicate that it is a vibrational level of the S[subscript 1-]cis isomer ([bar-over A][superscript 1]A[subscript 2]). Guided by ab initio calculations [J. H. Baraban, A. R. Beck, A. H. Steeves, J. F. Stanton, and R. W. Field, J. Chem. Phys. 134, 244311 (2011)]10.1063/1.3570823 of the cis-well vibrational frequencies, the vibrational assignments of these four levels can be established from their vibrational symmetries together with the [superscript 13]C isotope shift of the 46 175 cm[superscript −1] level (assigned here as cis-3[superscript 1]6[superscript 1]). The S[subscript 1]-cis zero-point level is deduced to lie near 44 900 cm[superscript −1], and the ν[subscript 6] vibrational frequency of the S[subscript 1]-cis well is found to be roughly 565 cm[superscript −1]; these values are in remarkably good agreement with the results of recent ab initio calculations. The 46 175 cm[superscript −1] vibrational level is found to have a 3.9 cm[superscript −1] staggering of its K-rotational structure as a result of quantum mechanical tunneling through the isomerization barrier. Such tunneling does not give rise to ammonia-type inversion doubling, because the cis and trans isomers are not equivalent; instead the odd-K, United States. Dept. of Energy (Grant DE-FG0287ER13671), National Science Foundation (U.S.). Graduate Research Fellowship Program

Rotational analyses are reported for a number of newly-discovered vibrational levels of the S1-trans [S subscriopt 1 -trans](Ã1Au) [A tilde superscript 1 A subscript u] state of C2H2 [C subscript 2 H subscript 2]. These levels are combinations where the Franck–Condon active v2' [v subscript 2 prime] and v3' [v subscript 3 prime] vibrational modes are excited together with the low-lying bending vibrations, v4' [v subscript 4 prime] and v6' [v subscript 6 prime]. The structures of the bands are complicated by strong a- and b-axis Coriolis coupling, as well as Darling–Dennison resonance for those bands that involve overtones of the bending vibrations. The most interesting result is the strong anharmonicity in the combinations of v3' [v subscript 3 prime] (trans bend, ag [a subscript g]) and v6' [v subscript 6 prime] (in-plane cis bend, bu [b subscript u]). This anharmonicity presumably represents the approach of the molecule to the trans–cis isomerization barrier, where ab initio results have predicted the transition state to be half-linear, corresponding to simultaneous excitation of v3' [v subscript 3 prime] and v6' [v subscript 6 prime]. The anharmonicity also causes difficulty in the least squares fitting of some of the polyads, because the simple model of Coriolis coupling and Darling–Dennison resonance starts to break down. The effective Darling–Dennison parameter, K4466 [K subscript 4466], is found to increase rapidly with excitation of v3' [v subscript 3 prime], while many small centrifugal distortion terms have had to be included in the least squares fits in order to reproduce the rotational structure correctly. Fermi resonances become important where the K-structures of different polyads overlap, as happens with the 2131B1 [2 superscript 1 3 superscript 1 B superscript 1] and 31B3 [3 superscript 1 B superscript 3] polyads (B = 4 or 6). The aim of this work is to establish the detailed vibrational level structure of the S1-trans [S subscript 1 -trans] state in, United States. Dept. of Energy (Grant DE-FG0287ER13671), Natural Sciences and Engineering Research Council of Canada (NSERC), National Science Council of Taiwan

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2009., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Vita., Includes bibliographical references (p. 259-271)., In this thesis, I demonstrate that measurements of electronic-structure-induced splittings in the rotational spectrum of a vibrationally excited state can identify the nature and extent of the distortion of the equilibrium electronic wavefunction and thereby provide a measure of progress along a reaction coordinate. One-dimensional models of the large amplitude bending reaction coordinates and their associated electronic signatures are constructed for two prototypical unimolecular isomerizations: acetylene<-->vinylidene (HCCH<-->CCH2), and hydrogen cyanide$hydrogen isocyanide (HCN<-->HNC). The nuclear quadrupole hyperne structures of HCN and HNC are distinct at their equilibrium geometries due to the dissimilar natures of bonding in the vicinity of the 14N nucleus. High resolution rotational spectroscopy has been used to determine the hyperne coupling parameters for the ground and excited vibrational levels of HCN and HNC, with up to ten quanta of bending excitation in HCN and up to four quanta in HNC. These spectra reveal the evolution of electronic structure along the isomerization path. Large amplitude local-bending vibrational eigenstates of the ... state of acetylene are shown to be unique in that they possess significant electric dipole moments as a result of the dynamical symmetry breaking in the local-mode limit. Stimulated emission pumping (SEP), through Franck{Condonforbidden vibrational levels of the A~ 1Au state, has been employed to populate the lowest few eigenstates that manifest large amplitude local-bending behavior., (cont.) Locating appropriate SEP intermediate states has required thorough analysis of the A~-state level structure, particularly the overtones and combination levels involving the nearly degenerate low frequency bending modes, 04 and 06, that are directly related to two possible paths for trans{cis isomerization on the excited state surface. Recent developments in chirped-pulse rotational spectroscopy will enable identification of the higher energy local-bending eigenstates, which approach the acetylene<-->vinylidene transition state, based on their predicted Stark coefficients., by Adam H. Steeves., Ph.D.