12 research outputs found
Where Does the Density Localize? Convergent Behavior for Global Hybrids, Range Separation, and DFT+U
Approximate density functional theory (DFT) suffers from many-electron self-
interaction error, otherwise known as delocalization error, that may be
diagnosed and then corrected through elimination of the deviation from exact
piecewise linear behavior between integer electron numbers. Although paths to
correction of energetic delocalization error are well- established, the impact
of these corrections on the electron density is less well-studied. Here, we
compare the effect on density delocalization of DFT+U, global hybrid tuning,
and range- separated hybrid tuning on a diverse test set of 32 transition metal
complexes and observe the three methods to have qualitatively equivalent
effects on the ground state density. Regardless of valence orbital diffuseness
(i.e., from 2p to 5p), ligand electronegativity (i.e., from Al to O), basis set
(i.e., plane wave versus localized basis set), metal (i.e., Ti, Fe, Ni) and
spin state, or tuning method, we consistently observe substantial charge loss
at the metal and gain at ligand atoms (ca. 0.3-0.5 e or more). This charge loss
at the metal is preferentially from the minority spin, leading to increasing
magnetic moment as well. Using accurate wavefunction theory references, we
observe that a minimum error in partial charges and magnetic moments occur at
higher tuning parameters than typically employed to eliminate energetic
delocalization error. These observations motivate the need to develop
multi-faceted approximate-DFT error correction approaches that separately treat
density delocalization and energetic errors in order to recover both correct
density and magnetization properties.Comment: 34 pages, 11 figure
Computational Discovery of Hydrogen Bond Design Rules for Electrochemical Ion Separation
Selective ion separation is a major challenge with far-ranging impact from water desalination to product separation in catalysis. Recently introduced ferrocene (Fc)/ferrocenium (Fc⁺) polymer electrode materials have been demonstrated experimentally and theoretically to selectively bind carboxylates over perchlorate through weak C–H···O hydrogen bond (HB) interactions that favor carboxylates, despite the comparable size and charge of the two species. However, practical application of this technology in aqueous environments requires further selectivity enhancement. Using a first-principles discovery approach, we investigate the effect of Fc/Fc⁺ functional groups (FGs) on the selectivity and reversibility of formate–Fc⁺ adsorption with respect to perchlorate in aqueous solution. Our wide design space of 44 FGs enables identification of FGs with higher selectivity and rationalization of trends through electronic energy decomposition analysis or geometric hydrogen bonding analysis. Overall, we observe weaker, longer HBs for perchlorate as compared to formate with Fc⁺. We further identify Fc⁺ functionalizations that simultaneously increase selectivity for formate in aqueous environments but permit rapid release from neutral Fc. We introduce the materiaphore, a 3D abstraction of these design rules, to help guide next-generation material optimization for selective ion sorption. This approach is expected to have broad relevance in computational discovery for molecular recognition, sensing, separations, and catalysis.National Science Foundation (U.S.) (ECCS-1449291
Why Pleiotropic Interventions are Needed for Alzheimer's Disease
Alzheimer's disease (AD) involves a complex pathological cascade thought to be initially triggered by the accumulation of β-amyloid (Aβ) peptide aggregates or aberrant amyloid precursor protein (APP) processing. Much is known of the factors initiating the disease process decades prior to the onset of cognitive deficits, but an unclear understanding of events immediately preceding and precipitating cognitive decline is a major factor limiting the rapid development of adequate prevention and treatment strategies. Multiple pathways are known to contribute to cognitive deficits by disruption of neuronal signal transduction pathways involved in memory. These pathways are altered by aberrant signaling, inflammation, oxidative damage, tau pathology, neuron loss, and synapse loss. We need to develop stage-specific interventions that not only block causal events in pathogenesis (aberrant tau phosphorylation, Aβ production and accumulation, and oxidative damage), but also address damage from these pathways that will not be reversed by targeting prodromal pathways. This approach would not only focus on blocking early events in pathogenesis, but also adequately correct for loss of synapses, substrates for neuroprotective pathways (e.g., docosahexaenoic acid), defects in energy metabolism, and adverse consequences of inappropriate compensatory responses (aberrant sprouting). Monotherapy targeting early single steps in this complicated cascade may explain disappointments in trials with agents inhibiting production, clearance, or aggregation of the initiating Aβ peptide or its aggregates. Both plaque and tangle pathogenesis have already reached AD levels in the more vulnerable brain regions during the “prodromal” period prior to conversion to “mild cognitive impairment (MCI).” Furthermore, many of the pathological events are no longer proceeding in series, but are going on in parallel. By the MCI stage, we stand a greater chance of success by considering pleiotropic drugs or cocktails that can independently limit the parallel steps of the AD cascade at all stages, but that do not completely inhibit the constitutive normal functions of these pathways. Based on this hypothesis, efforts in our laboratories have focused on the pleiotropic activities of omega-3 fatty acids and the anti-inflammatory, antioxidant, and anti-amyloid activity of curcumin in multiple models that cover many steps of the AD pathogenic cascade (Cole and Frautschy, Alzheimers Dement 2:284–286, 2006)
Understanding and Breaking Scaling Relations in Single-Site Catalysis: Methane to Methanol Conversion by Fe<sup>IV</sup>O
Computational high-throughput screening
is an essential tool for catalyst design, limited primarily by the
efficiency with which accurate predictions can be made. In bulk heterogeneous
catalysis, linear free energy relationships (LFERs) have been extensively
developed to relate elementary step activation energies, and thus
overall catalytic activity, back to the adsorption energies of key
intermediates, dramatically reducing the computational cost of screening.
The applicability of these LFERs to single-site catalysts remains
unclear, owing to the directional, covalent metal–ligand bonds
and the broader chemical space of accessible ligand scaffolds. Through
a computational screen of nearly 500 model Fe(II) complexes for CH<sub>4</sub> hydroxylation, we observe that (1) tuning ligand field strength
yields LFERs by comparably shifting energetics of the metal 3d levels
that govern the stability of different intermediates and (2) distortion
of the metal coordination geometry breaks these LFERs by increasing
the splitting between the d<sub><i>xz</i></sub>/d<sub><i>yz</i></sub> and d<sub><i>z</i><sup>2</sup></sub> metal
states that govern reactivity. Thus, in single-site catalysts, low
Brønsted–Evans–Polanyi slopes for oxo formation,
which would limit peak turnover frequency achievable through ligand
field tuning alone, can be overcome through structural distortions
achievable in experimentally characterized compounds. Observations
from this screen also motivate the placement of strong HB donors in
targeted positions as a scaffold-agnostic strategy for further activity
improvement. More generally, our findings motivate broader variation
of coordination geometries in reactivity studies with single-site
catalysts
Understanding and Breaking Scaling Relations in Single-Site Catalysis: Methane to Methanol Conversion by Fe<sup>IV</sup>O
Computational high-throughput screening
is an essential tool for catalyst design, limited primarily by the
efficiency with which accurate predictions can be made. In bulk heterogeneous
catalysis, linear free energy relationships (LFERs) have been extensively
developed to relate elementary step activation energies, and thus
overall catalytic activity, back to the adsorption energies of key
intermediates, dramatically reducing the computational cost of screening.
The applicability of these LFERs to single-site catalysts remains
unclear, owing to the directional, covalent metal–ligand bonds
and the broader chemical space of accessible ligand scaffolds. Through
a computational screen of nearly 500 model Fe(II) complexes for CH<sub>4</sub> hydroxylation, we observe that (1) tuning ligand field strength
yields LFERs by comparably shifting energetics of the metal 3d levels
that govern the stability of different intermediates and (2) distortion
of the metal coordination geometry breaks these LFERs by increasing
the splitting between the d<sub><i>xz</i></sub>/d<sub><i>yz</i></sub> and d<sub><i>z</i><sup>2</sup></sub> metal
states that govern reactivity. Thus, in single-site catalysts, low
Brønsted–Evans–Polanyi slopes for oxo formation,
which would limit peak turnover frequency achievable through ligand
field tuning alone, can be overcome through structural distortions
achievable in experimentally characterized compounds. Observations
from this screen also motivate the placement of strong HB donors in
targeted positions as a scaffold-agnostic strategy for further activity
improvement. More generally, our findings motivate broader variation
of coordination geometries in reactivity studies with single-site
catalysts
Unifying Exchange Sensitivity in Transition-Metal Spin-State Ordering and Catalysis through Bond Valence Metrics
Accurate predictions of spin-state
ordering, reaction energetics,
and barrier heights are critical for the computational discovery of
open-shell transition-metal (TM) catalysts. Semilocal approximations
in density functional theory, such as the generalized gradient approximation
(GGA), suffer from delocalization error that causes them to overstabilize
strongly bonded states. Descriptions of energetics and bonding are
often improved by introducing a fraction of exact exchange (e.g.,
erroneous low-spin GGA ground states are instead correctly predicted
as high-spin with a hybrid functional). The degree of spin-splitting
sensitivity to exchange can be understood based on the chemical composition
of the complex, but the effect of exchange on reaction energetics
within a single spin state is less well-established. Across a number
of model iron complexes, we observe strong exchange sensitivities
of reaction barriers and energies that are of the same magnitude as
those for spin splitting energies. We rationalize trends in both reaction
and spin energetics by introducing a measure of delocalization, the
bond valence of the metal–ligand bonds in each complex. The
bond valence thus represents a simple-to-compute property that unifies
understanding of exchange sensitivity for catalytic properties and
spin-state ordering in TM complexes. Close agreement of the resulting
per-metal–organic-bond sensitivity estimates, together with
failure of alternative descriptors demonstrates the utility of the
bond valence as a robust descriptor of how differences in metal–ligand
delocalization produce differing relative energetics with exchange
tuning. Our unified description explains the overall effect of exact
exchange tuning on the paradigmatic two-state FeO<sup>+</sup>/CH<sub>4</sub> reaction that combines challenges of spin-state and reactivity
predictions. This new descriptor-sensitivity relationship provides
a path to quantifying how predictions in transition-metal complex
screening are sensitive to the method used
Leveraging Cheminformatics Strategies for Inorganic Discovery: Application to Redox Potential Design
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<sup>+</sup> 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
Leveraging Cheminformatics Strategies for Inorganic Discovery: Application to Redox Potential Design
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<sup>+</sup> 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
Boundary Conditions for Promotion versus Poisoning in Copper-Gallium-based CO2–to–Methanol Hydrogenation Catalysts
Cu-Ga-based CO2-to-methanol hydrogenation catalysts are known to display a range of catalytic performance depending on their preparation. Here, using surface organometallic chemistry, we have prepared a series of silica-supported 3-6 nm Cu1-xGaxOy nanoparticles with a range of xGa to establish how the concentration of Ga and alloy formation affect the activity. Cu is always fully metallic in this series, while Ga is partially alloyed with Cu in the core and partially oxidized on the surface. These materials display a volcano-type activity behavior, where methanol formation is promoted when xGa < 0.13-0.18 and is suppressed at higher values, indicating a poisoning of the catalysts. In situ X-ray absorption spectroscopy shows that GaOx species over promoted Cu0.93Ga0.07-SiO2 catalyst are much more redox active than those over the poisoned Cu0.77Ga0.23-SiO2. In situ infrared spectroscopy detected methoxy intermediates over the promoted Cu0.93Ga0.07-SiO2 catalyst, while no formate or methoxy species could be observed over the poisoned Cu0.77Ga0.23-SiO2. The absence of reactive intermediates and irreversible oxidation of GaOx over poisoned catalyst suggests encapsulation of Cu by GaOx shell resulting in low activity