10 research outputs found
Solvent-Induced Red-Shifts for the Proton Stretch Vibrational Frequency in a Hydrogen-Bonded Complex. 1. A Valence Bond-Based Theoretical Approach
A theory is presented for the proton
stretch vibrational frequency
Îœ<sub>AH</sub> for hydrogen (Hâ) bonded complexes of
the acid dissociation type, that is, AH···B â
A<sup>â</sup>···HB<sup>+</sup>(but without complete
proton transfer), in both polar and nonpolar solvents, with special
attention given to the variation of Μ<sub>AH</sub> with the
solventâs dielectric constant Δ. The theory involves
a valence bond (VB) model for the complexâs electronic structure,
quantization of the complexâs proton and H-bond motions, and
a solvent coordinate accounting for nonequilibrium solvation. A general
prediction is that Μ<sub>AH</sub> decreases with increasing
Δ largely due to increased solvent stabilization of the ionic
VB structure A<sup>â</sup>···HB<sup>+</sup> relative
to the neutral VB structure AH···B. Theoretical Μ<sub>AH</sub> versus 1/Δ slope expressions are derived; these differ
for polar and nonpolar solvents and allow analysis of the solvent
dependence of Μ<sub>AH</sub>. The theory predicts that both
polar and nonpolar slopes are determined by (i) a structure factor
reflecting the complexâs size/geometry, (ii) the complexâs
dipole moment in the ground vibrational state, and (iii) the dipole
moment change in the transition, which especially reflects charge
transfer and the solution phase proton potential shapes. The experimental
proton frequency solvent dependence for several OH···O
H-bonded complexes is successfully accounted for and analyzed with
the theory
Dynamical Disorder in the DNA Hydration Shell
The reorientation
and hydrogen-bond dynamics of water molecules
within the hydration shell of a B-DNA dodecamer, which are of interest
for many of its biochemical functions, are investigated via molecular
dynamics simulations and an analytic jump model, which provide valuable
new molecular level insights into these dynamics. Different sources
of heterogeneity in the hydration shell dynamics are determined. First,
a pronounced spatial heterogeneity is found at the DNA interface and
explained via the jump model by the diversity in local DNA interfacial
topographies and DNAâwater H-bond interactions. While most
of the hydration shell is moderately retarded with respect to the
bulk, some water molecules confined in the narrow minor groove exhibit
very slow dynamics. An additional source of heterogeneity is found
to be caused by the DNA conformational fluctuations, which modulate
the water dynamics. The groove widening aids the approach of, and
the jump to, a new water H-bond partner. This temporal heterogeneity
is especially strong in the minor groove, where groove width fluctuations
occur on the same time scale as the water H-bond rearrangements, leading
to a strong dynamical disorder. The usual simplifying assumption that
hydration shell dynamics is much faster than DNA dynamics is thus
not valid; our results show that biomolecular conformational fluctuations
are essential to facilitate the water motions and accelerate the hydration
dynamics in confined groove sites
Predicting Hydride Donor Strength via Quantum Chemical Calculations of Hydride Transfer Activation Free Energy
We
propose a method to approximate the kinetic properties of hydride
donor species by relating the nucleophilicity (<i>N</i>)
of a hydride to the activation free energy <i>Î<i>G</i></i><sup>⧧</sup> of its corresponding hydride
transfer reaction. <i>N</i> is a kinetic parameter related
to the hydride transfer rate constant that quantifies a nucleophilic
hydridic speciesâ tendency to donate. Our method estimates <i>N</i> using quantum chemical calculations to compute <i>Î<i>G</i></i><sup>⧧</sup> for hydride
transfers from hydride donors to CO<sub>2</sub> in solution. A linear
correlation for each class of hydrides is then established between
experimentally determined <i>N</i> values and the computationally
predicted <i>Î<i>G</i></i><sup>⧧</sup>; this relationship can then be used to predict nucleophilicity for
different hydride donors within each class. This approach is employed
to determine <i>N</i> for four different classes of hydride
donors: two organic (carbon-based and benzimidazole-based) and two
inorganic (boron and silicon) hydride classes. We argue that silicon
and boron hydrides are driven by the formation of the more stable
SiâO or BâO bond. In contrast, the carbon-based hydrides
considered herein are driven by the stability acquired upon rearomatization,
a feature making these species of particular interest, because they
both exhibit catalytic behavior and can be recycled
Dihydropteridine/Pteridine as a 2H<sup>+</sup>/2e<sup>â</sup> Redox Mediator for the Reduction of CO<sub>2</sub> to Methanol: A Computational Study
Conflicting
experimental results for the electrocatalytic reduction
of CO<sub>2</sub> to CH<sub>3</sub>OH on a glassy carbon electrode
by the 6,7-dimethyl-4-hydroxy-2-mercaptopteridine have been recently
reported [J. Am. Chem. Soc. 2014, 136, 14007â14010, J. Am. Chem. Soc. 2016, 138, 1017â1021]. In
this connection, we have used computational chemistry to examine the
issue of this moleculeâs ability to act as a hydride donor
to reduce CO<sub>2</sub>. We first determined that the most thermodynamically
stable tautomer of this aqueous compound is its oxothione form, termed
here PTE. It is argued that this species electrochemically undergoes
concerted 2H<sup>+</sup>/2e<sup>â</sup> transfers to first
form the kinetic product 5,8-dihydropteridine, followed by acid-catalyzed
tautomerization to the thermodynamically more stable 7,8-dihydropteridine
PTEH<sub>2</sub>. While the overall conversion of CO<sub>2</sub> to
CH<sub>3</sub>OH by three successive hydride and proton transfers
from this most stable tautomer is computed to be exergonic by 5.1
kcal/mol, we predict high activation free energies (Î<i>G</i><sup>âĄ</sup><sub>HT</sub>) of 29.0 and 29.7 kcal/mol
for the homogeneous reductions of CO<sub>2</sub> and its intermediary
formic acid product by PTE/PTEH<sub>2</sub>, respectively. These high
barriers imply that PTE/PTEH<sub>2</sub> is unable, by this mechanism,
to homogeneously reduce CO<sub>2</sub> on a time scale of hours at
room temperature
Roles of the Lewis Acid and Base in the Chemical Reduction of CO<sub>2</sub> Catalyzed by Frustrated Lewis Pairs
We employ quantum
chemical calculations to discover how frustrated Lewis pairs (FLP)
catalyze the reduction of CO<sub>2</sub> by ammonia borane (AB); specifically,
we examine how the Lewis acid (LA) and Lewis base (LB) of an FLP activate
CO<sub>2</sub> for reduction. We find that the LA (trichloroaluminum,
AlCl<sub>3</sub>) alone catalyzes hydride transfer (HT) to CO<sub>2</sub> while the LB (trimesitylenephosphine, PMes<sub>3</sub>) actually
hinders HT; inclusion of the LB increases the HT barrier by âŒ8
kcal/mol relative to the reaction catalyzed by LAs only. The LB hinders
HT by donating its lone pair to the LUMO of CO<sub>2</sub>, increasing
the electron density on the C atom and thus lowering its hydride affinity.
Although the LB hinders HT, it nonetheless plays a crucial role by
stabilizing the active FLP·CO<sub>2</sub> complex relative to
the LA dimer, free CO<sub>2</sub>, and free LB. This greatly increases
the concentration of the reactive complex in the form FLP·CO<sub>2</sub> and thus increases the rate of reaction. We expect that the
principles we describe will aid in understanding other catalytic CO<sub>2</sub> reductions
Reduction of CO<sub>2</sub> to Methanol Catalyzed by a Biomimetic Organo-Hydride Produced from Pyridine
We use quantum chemical calculations
to elucidate a viable mechanism
for pyridine-catalyzed reduction of CO<sub>2</sub> to methanol involving
homogeneous catalytic steps. The first phase of the catalytic cycle
involves generation of the key catalytic agent, 1,2-dihydropyridine
(<b>PyH</b><sub><b>2</b></sub>). First, pyridine (Py)
undergoes a H<sup>+</sup> transfer (PT) to form pyridinium (PyH<sup>+</sup>), followed by an e<sup>â</sup> transfer (ET) to produce
pyridinium radical (PyH<sup>0</sup>). Examples of systems to effect
this ET to populate PyH<sup>+</sup>âs LUMO (<i>E</i><sup>0</sup><sub>calc</sub> ⌠â1.3 V vs SCE) to form
the solution phase PyH<sup>0</sup> via highly reducing electrons include
the photoelectrochemical p-GaP system (<i>E</i><sub>CBM</sub> ⌠â1.5 V vs SCE at pH 5) and the photochemical [RuÂ(phen)<sub>3</sub>]<sup>2+</sup>/ascorbate system. We predict that PyH<sup>0</sup> undergoes further PTâET steps to form the key closed-shell,
dearomatized (<b>PyH</b><sub><b>2</b></sub>) species (with
the PT capable of being assisted by a negatively biased cathode).
Our proposed sequential PTâETâPTâET mechanism
for transforming Py into <b>PyH</b><sub><b>2</b></sub> is analogous to that described in the formation of related dihydropyridines.
Because it is driven by its proclivity to regain aromaticity, <b>PyH</b><sub><b>2</b></sub> is a potent recyclable organo-hydride
donor that mimics important aspects of the role of NADPH in the formation
of CâH bonds in the photosynthetic CO<sub>2</sub> reduction
process. In particular, in the second phase of the catalytic cycle,
which involves three separate reduction steps, we predict that the <b>PyH</b><sub><b>2</b></sub>/Py redox couple is kinetically
and thermodynamically competent in catalytically effecting hydride
and proton transfers (the latter often mediated by a proton relay
chain) to CO<sub>2</sub> and its two succeeding intermediates, namely,
formic acid and formaldehyde, to ultimately form CH<sub>3</sub>OH.
The hydride and proton transfers for the first of these reduction
steps, the homogeneous reduction of CO<sub>2</sub>, are sequential
in nature (in which the formate to formic acid protonation can be
assisted by a negatively biased cathode). In contrast, these transfers
are coupled in each of the two subsequent homogeneous hydride and
proton transfer steps to reduce formic acid and formaldehyde
Multistep Drug Intercalation: Molecular Dynamics and Free Energy Studies of the Binding of Daunomycin to DNA
Atomic-scale molecular dynamics and free energy calculations
in
explicit aqueous solvent are used to study the complex mechanism by
which a molecule can intercalate between successive base pairs of
the DNA double helix. We have analyzed the intercalation pathway for
the anticancer drug daunomycin using two different methods: metadynamics
and umbrella sampling. The resulting free energy pathways are found
to be consistent with one another and point, within an equilibrium
free energy context, to a three-step process. Daunomycin initially
binds in the minor groove of DNA. An activated step then leads to
rotation of the drug, coupled with DNA deformation that opens a wedge
between the base pairs, bends DNA toward the major groove, and forms
a metastable intermediate that resembles structures seen within the
interfaces between DNA and minor-groove-binding proteins. Finally,
crossing a small free energy barrier leads to further rotation of
daunomycin and full intercalation of the drug, reestablishing stacking
with the flanking base pairs and straightening the double helix
Reaction Mechanism for Direct Proton Transfer from Carbonic Acid to a Strong Base in Aqueous Solution I: Acid and Base Coordinate and Charge Dynamics
Protonation
by carbonic acid H<sub>2</sub>CO<sub>3</sub> of the
strong base methylamine CH<sub>3</sub>NH<sub>2</sub> in a neutral
contact pair in aqueous solution is followed via CarâParrinello
molecular dynamics simulations. Proton transfer (PT) occurs to form
an aqueous solvent-stabilized contact ion pair within 100 fs, a fast
time scale associated with the compression of the acidâbase
hydrogen-bond (H-bond), a key reaction coordinate. This rapid barrierless
PT is consistent with the carbonic acid-protonated base p<i>K</i><sub>a</sub> difference that considerably favors the PT, and supports
the view of intact carbonic acid as potentially important proton donor
in assorted biological and environmental contexts. The charge redistribution
within the H-bonded complex during PT supports a Mulliken picture
of charge transfer from the nitrogen base to carbonic acid without
altering the transferring hydrogenâs charge from approximately
midway between that of a hydrogen atom and that of a proton
Reaction Mechanism for Direct Proton Transfer from Carbonic Acid to a Strong Base in Aqueous Solution II: Solvent Coordinate-Dependent Reaction Path
The
protonation of methylamine base CH<sub>3</sub>NH<sub>2</sub> by carbonic
acid H<sub>2</sub>CO<sub>3</sub> within a hydrogen (H)-bonded
complex in aqueous solution was studied via CarâParrinello
dynamics in the preceding paper (Daschakraborty, S.; Kiefer, P. M.;
Miller, Y.; Motro, Y.; Pines, D.; Pines, E.; Hynes, J. T. <i>J. Phys. Chem. B</i> <b>2016</b>, DOI: 10.1021/acs.jpcb.5b12742). Here some important further details of the reaction path are presented,
with specific emphasis on the water solventâs role. The overall
reaction is barrierless and very rapid, on an âŒ100 fs time
scale, with the proton transfer (PT) event itself being very sudden
(<10 fs). This transfer is preceded by the acidâbase H-bondâs
compression, while the water solvent changes little until the actual
PT occurrence; this results from the very strong driving force for
the reaction, as indicated by the very favorable acid-protonated base
Îp<i>K</i><sub>a</sub> difference. Further solvent
rearrangement follows immediately the sudden PTâs production
of an incipient contact ion pair, stabilizing it by establishment
of equilibrium solvation. The solvent waterâs short time scale
âŒ120 fs response to the incipient ion pair formation is primarily
associated with librational modes and H-bond compression of water
molecules around the carboxylate anion and the protonated base. This
is consistent with this stabilization involving significant increase
in H-bonding of hydration shell waters to the negatively charged carboxylate
group oxygensâ (especially the former H<sub>2</sub>CO<sub>3</sub> donor oxygen) and the nitrogen of the positively charged protonated
baseâs NH<sub>3</sub><sup>+</sup>
Benzimidazoles as Metal-Free and Recyclable Hydrides for CO2 Reduction to Formate
We report a novel metal-free chemical reduction of CO2 by a recyclable benzimidazole-based organo-hydride, whose choice was guided by quantum chemical calculations. Notably, benzimidazole-based hydride donors rival the hydride-donating abilities of noble metal-based hydrides such as [Ru(tpy)(bpy)H]+ and [Pt(depe)2H]+. Chemical CO2 reduction to the formate anion (HCOO) was carried out in the absence of biological enzymes, a sacrificial Lewis acid, or a base to activate the substrate or reductant. 13CO2 experiments confirmed the formation of H13COO by CO2 reduction with the formate product characterized by 1H-NMR and 13C-NMR spectroscopies, and ESI-MS. The highest formate yield of 66% was obtained in the presence of potassium tetrafluoroborate under mild conditions. The likely role of exogenous salt additives in this reaction is to stabilize and shift the equilibrium towards the ionic products. After CO2 reduction, the benzimidazole-based hydride donor was quantitatively oxidized to its aromatic benzimidazolium cation, establishing its recyclability. In addition, we electrochemically reduced the benzimidazolium cation to its organo-hydride form in quantitative yield, demonstrating its potential for electrocatalytic CO2 reduction. These results serve as a proof of concept for the electrocatalytic reduction of CO2 by sustainable, recyclable and metal-free organo-hydrides