Systemic deficits in lipid homeostasis promote aging-associated impairments in B cell progenitor development.

Organismal aging has been associated with diverse metabolic and functional changes across tissues. Within the immune system, key features of physiological hematopoietic cell aging include increased fat deposition in the bone marrow, impaired hematopoietic stem and progenitor cell (HSPC) function, and a propensity towards myeloid differentiation. This shift in lineage bias can lead to pre-malignant bone marrow conditions such as clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenias of undetermined significance (CCUS), frequently setting the stage for subsequent development of age-related cancers in myeloid or lymphoid lineages.

Predicting 35-Cl electric field gradient tensors in crystalline solids using cluster and fragment-corrected planewave density functional theory.

Planewave-corrected methods have proven effective for accurately modeling nuclear magnetic resonance (NMR) parameters in crystalline systems. Recent work extended the application of planewave-corrected calculations beyond the second row, predicting EFG tensor parameters for Cl using a simple molecular correction to projector augmented-wave (PAW) density functional theory (DFT). Here we extend this work using fragment and cluster-based calculations coupled with polarizable continuum (PCM) methods to improve further the accuracy of planewave-corrected Cl EFG tensor calculations.

Predicting V nuclear magnetic resonance observables in molecular crystals.

Solid-state nuclear magnetic resonance (NMR) spectroscopy and quantum chemical density functional theory (DFT) calculations are widely used to characterize vanadium centers in biological and pharmaceutically relevant compounds. Several techniques have been recently developed to improve the accuracy of predicted NMR parameters obtained from DFT. Fragment-based and planewave-corrected methods employing hybrid density functionals are particularly effective tools for solid-state applications.

Selective anion sensing in high salt water a remote indicator displacement assay.

Water-soluble deep cavitands with cationic functions at the lower rim can selectively bind iodide anions in purely aqueous solution. By pairing this lower rim recognition with an indicator dye that is bound in the host cavity, optical sensing of anions is possible. The selectivity for iodide is high enough that micromolar concentrations of iodide can be detected in the presence of molar chloride.

Do Models beyond Hybrid Density Functionals Increase the Agreement with Experiment for Predicted NMR Chemical Shifts or Electric Field Gradient Tensors in Organic Solids?

predictions of chemical shifts and electric field gradient (EFG) tensor components are frequently used to help interpret solid-state nuclear magnetic resonance (NMR) experiments. Typically, these predictions employ density functional theory (DFT) with generalized gradient approximation (GGA) functionals, though hybrid functionals have been shown to improve accuracy relative to experiment. Here, the performance of a dozen models beyond the GGA approximation are examined for the prediction of solid-state NMR observables, including meta-GGA, hybrid, and double-hybrid density functionals and second-order Møller-Plesset perturbation theory (MP2).

Benchmark accuracy of predicted NMR observables for quadrupolar N and O nuclei in molecular crystals.

Nuclear quadrupole resonances for and O nuclei are exquisitely sensitive to interactions with surrounding atoms. As a result, nitrogen and oxygen solid-state nuclear magnetic resonance (ssNMR) provides a powerful tool for investigating structure and dynamics in complex systems. First-principles calculations are increasingly used to facilitate spectral assignment and to evaluate and adjust crystal structures.

Improving the accuracy of GIPAW chemical shielding calculations with cluster and fragment corrections.

Ab initio methods for predicting NMR parameters in the solid state are an essential tool for assigning experimental spectra and play an increasingly important role in structural characterizations. Recently, a molecular correction (MC) technique has been developed which combines the strengths of plane-wave methods (GIPAW) with single molecule calculations employing Gaussian basis sets. The GIPAW + MC method relies on a periodic calculation performed at a lower level of theory to model the crystalline environment.

Fast and Accurate Electric Field Gradient Calculations in Molecular Solids With Density Functional Theory.

Modern approaches for calculating electric field gradient (EFF) tensors in molecular solids rely upon plane-wave calculations employing periodic boundary conditions (PBC). In practice, models employing PBCs are limited to generalized gradient approximation (GGA) density functionals. Hybrid density functionals applied in the context of gauge-including atomic orbital (GIAO) calculations have been shown to substantially improve the accuracy of predicted NMR parameters.

Bridging photochemistry and photomechanics with NMR crystallography: the molecular basis for the macroscopic expansion of an anthracene ester nanorod.

Crystals composed of photoreactive molecules represent a new class of photomechanical materials with the potential to generate large forces on fast timescales. An example is the photodimerization of 9--butyl-anthracene ester () in molecular crystal nanorods that leads to an average elongation of 8%. Previous work showed that this expansion results from the formation of a metastable crystalline product.

Accurate fragment-based 51-V chemical shift predictions in molecular crystals.

Nuclear magnetic resonance (NMR) spectroscopy plays a crucial role in determining molecular structure for complex biological and pharmaceutical compounds. NMR investigations are increasingly reliant on computation for mapping spectral features to chemical structures. Here we benchmark the accuracy of fragment-based V chemical shielding tensor calculations using a training set comprised of 10 biologically and pharmaceutically relevant oxovanadium complexes.

Modeling Small Structural and Environmental Differences in Solids with N NMR Chemical Shift Tensors.

The ability to theoretically predict accurate NMR chemical shifts in solids is increasingly important due to the role such shifts play in selecting among proposed model structures. Herein, two theoretical methods are evaluated for their ability to assign N shifts from guanosine dihydrate to one of the two independent molecules present in the lattice. The NMR data consist of N shift tensors from 10 resonances.

Accurate 13-C and 15-N molecular crystal chemical shielding tensors from fragment-based electronic structure theory.

Standard nuclear magnetic resonance (NMR) spectroscopy experiments measure isotropic chemical shifts, but measuring the chemical shielding anisotropy (CSA) tensor can provide additional insights into solid state chemical structures. Interpreting the principal components of these tensors is facilitated by first-principles chemical shielding tensor predictions. Here, the ability to predict molecular crystal CSA tensor components for C and N nuclei with fragment-based electronic structure techniques is explored.

Improved Electrostatic Embedding for Fragment-Based Chemical Shift Calculations in Molecular Crystals.

Fragment-based methods predict nuclear magnetic resonance (NMR) chemical shielding tensors in molecular crystals with high accuracy and computational efficiency. Such methods typically employ electrostatic embedding to mimic the crystalline environment, and the quality of the results can be sensitive to the embedding treatment. To improve the quality of this embedding environment for fragment-based molecular crystal property calculations, we borrow ideas from the embedded ion method to incorporate self-consistently polarized Madelung field effects.

Enhanced NMR Discrimination of Pharmaceutically Relevant Molecular Crystal Forms through Fragment-Based Ab Initio Chemical Shift Predictions.

Chemical shift prediction plays an important role in the determination or validation of crystal structures with solid-state nuclear magnetic resonance (NMR) spectroscopy. One of the fundamental theoretical challenges lies in discriminating variations in chemical shifts resulting from different crystallographic environments. Fragment-based electronic structure methods provide an alternative to the widely used plane wave gauge-including projector augmented wave (GIPAW) density functional technique for chemical shift prediction.

Predicting Molecular Crystal Properties from First Principles: Finite-Temperature Thermochemistry to NMR Crystallography.

Molecular crystals occur widely in pharmaceuticals, foods, explosives, organic semiconductors, and many other applications. Thanks to substantial progress in electronic structure modeling of molecular crystals, attention is now shifting from basic crystal structure prediction and lattice energy modeling toward the accurate prediction of experimentally observable properties at finite temperatures and pressures. This Account discusses how fragment-based electronic structure methods can be used to model a variety of experimentally relevant molecular crystal properties.

Benchmark fragment-based (1)H, (13)C, (15)N and (17)O chemical shift predictions in molecular crystals.

The performance of fragment-based ab initio(1)H, (13)C, (15)N and (17)O chemical shift predictions is assessed against experimental NMR chemical shift data in four benchmark sets of molecular crystals. Employing a variety of commonly used density functionals (PBE0, B3LYP, TPSSh, OPBE, PBE, TPSS), we explore the relative performance of cluster, two-body fragment, and combined cluster/fragment models. The hybrid density functionals (PBE0, B3LYP and TPSSh) generally out-perform their generalized gradient approximation (GGA)-based counterparts.

Fragment-Based Electronic Structure Approach for Computing Nuclear Magnetic Resonance Chemical Shifts in Molecular Crystals.

First-principles chemical shielding tensor predictions play a critical role in studying molecular crystal structures using nuclear magnetic resonance. Fragment-based electronic structure methods have dramatically improved the ability to model molecular crystal structures and energetics using high-level electronic structure methods. Here, a many-body expansion fragment approach is applied to the calculation of chemical shielding tensors in molecular crystals.

Fragment-based (13)C nuclear magnetic resonance chemical shift predictions in molecular crystals: An alternative to planewave methods.

We assess the quality of fragment-based ab initio isotropic (13)C chemical shift predictions for a collection of 25 molecular crystals with eight different density functionals. We explore the relative performance of cluster, two-body fragment, combined cluster/fragment, and the planewave gauge-including projector augmented wave (GIPAW) models relative to experiment. When electrostatic embedding is employed to capture many-body polarization effects, the simple and computationally inexpensive two-body fragment model predicts both isotropic (13)C chemical shifts and the chemical shielding tensors as well as both cluster models and the GIPAW approach.

Converging nuclear magnetic shielding calculations with respect to basis and system size in protein systems.

Ab initio chemical shielding calculations greatly facilitate the interpretation of nuclear magnetic resonance (NMR) chemical shifts in biological systems, but the large sizes of these systems requires approximations in the chemical models used to represent them. Achieving good convergence in the predicted chemical shieldings is necessary before one can unravel how other complex structural and dynamical factors affect the NMR measurements. Here, we investigate how to balance trade-offs between using a better basis set or a larger cluster model for predicting the chemical shieldings of the substrates in two representative examples of protein-substrate systems involving different domains in tryptophan synthase: the N-(4'-trifluoromethoxybenzoyl)-2-aminoethyl phosphate (F9) ligand which binds in the α active site, and the 2-aminophenol quinonoid intermediate formed in the β active site.

Dipole-mediated rectification of intramolecular photoinduced charge separation and charge recombination.

Controlling charge transfer at a molecular scale is critical for efficient light harvesting, energy conversion, and nanoelectronics. Dipole-polarization electrets, the electrostatic analogue of magnets, provide a means for "steering" electron transduction via the local electric fields generated by their permanent electric dipoles. Here, we describe the first demonstration of the utility of anthranilamides, moieties with ordered dipoles, for controlling intramolecular charge transfer.