26 research outputs found
Coarse-Grained Theory of Biological Charge Transfer with Spatially and Temporally Correlated Noise
Systemâenvironment interactions
are essential in determining
charge-transfer (CT) rates and mechanisms. We developed a computationally
accessible method, suitable to simulate CT in flexible molecules (i.e.,
DNA) with hundreds of sites, where the systemâenvironment interactions
are explicitly treated with numerical noise modeling of time-dependent
site energies and couplings. The properties of the noise are tunable,
providing us a flexible tool to investigate the detailed effects of
correlated thermal fluctuations on CT mechanisms. The noise is parametrizable
by molecular simulation and quantum calculation results of specific
molecular systems, giving us better molecular resolution in simulating
the systemâenvironment interactions than sampling fluctuations
from generic spectral density functions. The spatially correlated
thermal fluctuations among different sites are naturally built-in
in our method but are not readily incorporated using approximate spectral
densities. Our method has quantitative accuracy in systems with small
redox potential differences (<<i>k</i><sub>b</sub><i>T</i>) and provides qualitative insights into systems with wide
redox potential differences (â«<i>k</i><sub>b</sub><i>T</i>). Specifically, we find that the temporal correlations
of site energies are critical in determining the coherentâincoherent
transition, while the role of spatial correlations depends on the
nature of the systems. In a system with repeated bridge units of the
same chemistry, spatially correlated fluctuations enhance the charge
delocalization and charge-transfer rates; however, in a system of
units with different site energies, spatial correlations slow the
fluctuations to bring units into degeneracy, in turn, slowing the
charge-transfer rates. The spatial and temporal correlations of condensed
phase medium fluctuations provide another source to control and tune
the kinetics and dynamics of charge-transfer systems
Strategy To Discover Diverse Optimal Molecules in the Small Molecule Universe
The
small molecule universe (SMU) is defined as a set of over 10<sup>60</sup> synthetically feasible organic molecules with molecular weight less
than âŒ500 Da. Exhaustive enumerations and evaluation of all
SMU molecules for the purpose of discovering favorable structures
is impossible. We take a stochastic approach and extend the ACSESS
framework (Virshup et al. J. Am. Chem. Soc. 2013, 135, 7296â7303) to
develop diversity oriented molecular libraries that can generate
a set of compounds that is representative of the small molecule universe
and that also biases the library toward favorable physical property
values. We show that the approach is efficient compared to exhaustive
enumeration and to existing evolutionary algorithms for generating
such libraries by testing in the NKp fitness landscape model and in
the fully enumerated GDB-9 chemical universe containing 3 Ă 10<sup>5</sup> molecules
Biochemistry and Theory of Proton-Coupled Electron Transfer
Biochemistry and Theory of Proton-Coupled Electron
Transfe
Two-Electron Transfer Pathways
The
frontiers of electron-transfer chemistry demand that we develop theoretical
frameworks to describe the delivery of multiple electrons, atoms,
and ions in molecular systems. When electrons move over long distances
through high barriers, where the probability for thermal population
of oxidized or reduced bridge-localized states is very small, the
electrons will tunnel from the donor (D) to acceptor (A), facilitated
by bridge-mediated superexchange interactions. If the stable donor
and acceptor redox states on D and A differ by two electrons, it is
possible that the electrons will propagate coherently from D to A.
While structureâfunction relations for single-electron superexchange
in molecules are well established, strategies to manipulate the coherent
flow of multiple electrons are largely unknown. In contrast to one-electron
superexchange, two-electron superexchange involves both one- and two-electron
virtual intermediate states, the number of virtual intermediates increases
very rapidly with system size, and multiple classes of pathways interfere
with one another. In the study described here, we developed simple
superexchange models for two-electron transfer. We explored how the
bridge structure and energetics influence multielectron superexchange,
and we compared two-electron superexchange interactions to single-electron
superexchange. Multielectron superexchange introduces interference
between singly and doubly oxidized (or reduced) bridge virtual states,
so that even simple linear donorâbridgeâacceptor systems
have pathway topologies that resemble those seen for one-electron
superexchange through bridges with multiple parallel pathways. The
simple model systems studied here exhibit a richness that is amenable
to experimental exploration by manipulating the multiple pathways,
pathway crosstalk, and changes in the number of donor and acceptor
species. The features that emerge from these studies may assist in
developing new strategies to deliver multiple electrons in condensed-phase
redox systems, including multiple-electron redox species, multimetallic/multielectron
redox catalysts, and multiexciton excited states
Chirality Control of Electron Transfer in Quantum Dot Assemblies
Electron spin and molecular chirality
are emerging as factors that
can be used effectively to direct charge flow at the molecular scale.
We report order of magnitude effects of molecular chirality on electron-transfer
rates between quantum dots (QDs) in chiral QD assemblies. Indeed,
both the circular polarization of the light that excites the electron
donor and the imprinted chirality of the acceptor QDs affect the dot-to-dot
electron-transfer kinetics. We define a polarization for the electron-transfer
rate constant and show that it correlates with the strength of the
acceptor QD circular dichroism (CD) spectrum. These findings imply
that the CD strength of the QD exciton transition(s) may be used as
a predictor for the spin-dependent electron transfer, indicating that
chiral imprinting of the dots may lie at the origin of this phenomenon
Stochastic Voyages into Uncharted Chemical Space Produce a Representative Library of All Possible Drug-Like Compounds
The âsmall molecule universeâ
(SMU), the set of all
synthetically feasible organic molecules of 500 Da molecular weight
or less, is estimated to contain over 10<sup>60</sup> structures,
making exhaustive searches for structures of interest impractical.
Here, we describe the construction of a ârepresentative universal
libraryâ spanning the SMU that samples the full extent of feasible
small molecule chemistries. This library was generated using the newly
developed Algorithm for Chemical Space Exploration with Stochastic
Search (ACSESS). ACSESS makes two important contributions to chemical
space exploration: it allows the systematic search of the unexplored
regions of the small molecule universe, and it facilitates the mining
of chemical libraries that do not yet exist, providing a near-infinite
source of diverse novel compounds
Where Is the Electronic Oscillator Strength? Mapping Oscillator Strength across Molecular Absorption Spectra
The effectiveness of solar energy
capture and conversion materials
derives from their ability to absorb light and to transform the excitation
energy into energy stored in free carriers or chemical bonds. The
ThomasâReicheâKuhn (TRK) sum rule mandates that the
integrated (electronic) oscillator strength of an absorber equals
the total number of electrons in the structure. Typical molecular
chromophores place only about 1% of their oscillator strength in the
UVâvis window, so individual chromophores operate at about
1% of their theoretical limit. We explore the distribution of oscillator
strength as a function of excitation energy to understand this circumstance.
To this aim, we use familiar independent-electron model Hamiltonians
as well as first-principles electronic structure methods. While model
Hamiltonians capture the qualitative electronic spectra associated
with Ï electron chromophores, these Hamiltonians mistakenly
focus the oscillator strength in the fewest low-energy transitions.
Advanced electronic structure methods, in contrast, spread the oscillator
strength over a very wide excitation energy range, including transitions
to Rydberg and continuum states, consistent with experiment. Our analysis
rationalizes the low oscillator strength in the UVâvis spectral
region in molecules, a step toward the goal of oscillator strength
manipulation and focusing
Determinants of Photolyaseâs DNA Repair Mechanism in Mesophiles and Extremophiles
Light-driven DNA
repair by extremophilic photolyases is of tremendous
importance for understanding the early development of life on Earth.
The mechanism for flavin adenine dinucleotide repair of DNA lesions
is the subject of debate and has been studied mainly in mesophilic
species. In particular, the role of adenine in the repair process
is poorly understood. Using molecular docking, molecular dynamics
simulations, electronic structure calculations, and electron tunneling
pathways analysis, we examined adenineâs role in DNA repair
in four photolyases that thrive at different temperatures. Our results
indicate that the contribution of adenine to the electronic coupling
between the flavin and the cyclobutane pyrimidine dimer lesion to
be repaired is significant in three (one mesophilic and two extremophilic)
of the four enzymes studied. Our analysis suggests that thermophilic
and hyperthermophilic photolyases have evolved structurally to preserve
the functional position (and thus the catalytic function) of adenine
at their high temperatures of operation. Water molecules can compete
with adenine in establishing the strongest coupling pathway for the
electron transfer repair process, but the adenine contribution remains
substantial. The present study also reconciles prior seemingly contradictory
conclusions on the role of adenine in mesophile electron transfer
repair reactions, showing how adenine-mediated superexchange is conformationally
gated
Stochastic Voyages into Uncharted Chemical Space Produce a Representative Library of All Possible Drug-Like Compounds
The âsmall molecule universeâ
(SMU), the set of all
synthetically feasible organic molecules of 500 Da molecular weight
or less, is estimated to contain over 10<sup>60</sup> structures,
making exhaustive searches for structures of interest impractical.
Here, we describe the construction of a ârepresentative universal
libraryâ spanning the SMU that samples the full extent of feasible
small molecule chemistries. This library was generated using the newly
developed Algorithm for Chemical Space Exploration with Stochastic
Search (ACSESS). ACSESS makes two important contributions to chemical
space exploration: it allows the systematic search of the unexplored
regions of the small molecule universe, and it facilitates the mining
of chemical libraries that do not yet exist, providing a near-infinite
source of diverse novel compounds
Determinants of Photolyaseâs DNA Repair Mechanism in Mesophiles and Extremophiles
Light-driven DNA
repair by extremophilic photolyases is of tremendous
importance for understanding the early development of life on Earth.
The mechanism for flavin adenine dinucleotide repair of DNA lesions
is the subject of debate and has been studied mainly in mesophilic
species. In particular, the role of adenine in the repair process
is poorly understood. Using molecular docking, molecular dynamics
simulations, electronic structure calculations, and electron tunneling
pathways analysis, we examined adenineâs role in DNA repair
in four photolyases that thrive at different temperatures. Our results
indicate that the contribution of adenine to the electronic coupling
between the flavin and the cyclobutane pyrimidine dimer lesion to
be repaired is significant in three (one mesophilic and two extremophilic)
of the four enzymes studied. Our analysis suggests that thermophilic
and hyperthermophilic photolyases have evolved structurally to preserve
the functional position (and thus the catalytic function) of adenine
at their high temperatures of operation. Water molecules can compete
with adenine in establishing the strongest coupling pathway for the
electron transfer repair process, but the adenine contribution remains
substantial. The present study also reconciles prior seemingly contradictory
conclusions on the role of adenine in mesophile electron transfer
repair reactions, showing how adenine-mediated superexchange is conformationally
gated