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At least 343 records · Page 19

Phylogenomics reveals convergent evolution of red-violet coloration in land plants and the origins of the anthocyanin biosynthetic pathway

The flavonoids, one of the largest classes of plant secondary metabolites, are found in lineages that span the land plant phylogeny and play important roles in stress responses and as pigments. Perhaps the most well-studied flavonoids are the anthocyanins that have human health benefits and help plants attract pollinators, regulate hormone production, and confer resistance to abiotic and biotic stresses. The canonical biochemical pathway responsible for the production of these pigments is well-characterized for flowering plants yet its conservation across deep divergences in land plants remains debated and poorly understood. Many early land plants such as mosses, liverworts, and ferns produce flavonoid pigments, but their biosynthetic origins and homologies to the anthocyanin pathway remain uncertain. We conducted phylogenetic analyses using full genome sequences representing nearly all major green plant lineages to reconstruct the evolutionary history of the anthocyanin biosynthetic pathway then test the hypothesis that genes in this pathway are present in early land plants. We found that the entire pathway was not intact until the most recent common ancestor of seed plants and that orthologs of many downstream enzymes are absent from seedless plants including mosses, liverworts, and ferns. Our results also highlight the utility of phylogenetic inference, as compared to pairwise sequence similarity, in orthology assessment within large gene families that have complex duplication-loss histories. Here, we suggest that the production of red-violet flavonoid pigments widespread in seedless plants, including the 3-deoxyanthocyanins, requires the activity of novel, as-yet discovered enzymes, and represents convergent evolution of red-violet coloration across land plants.

59 BASIC BIOLOGICAL SCIENCES↗

Using low-coverage whole genome sequencing (genome skimming) to delineate three introgressed species of buffalofish ( Ictiobus )

Consumption of buffalofish has been sporadically associated with Haff disease-like illnesses involving sudden onset muscle pain and weakness due to skeletal muscle rhabdomyolysis, but determination of precisely which species are associated with these illnesses has been impeded by a lack of species-specific DNA-based markers. Here, three closely related species of buffalofish native to the Mississippi River Basin (Ictiobus bubalus, Ictiobus cyprinellus and Ictiobus niger) that have previously proven genetically indistinguishable using both mitochondrial and nuclear single-locus sequencing were reliably discriminated using low-coverage whole genome sequencing (‘genome skimming’). Using 44 specimens representing the three species collected from the mid/upper (Missouri) and lower (Louisiana) regions of the species’ native ranges, the SISRS (Site Identification from Short Read Sequences) bioinformatics pipeline was adapted to (1) identify over 620Mbp of putatively homologous nuclear sequence data and (2) isolate over 140,000 single-nucleotide polymorphisms (SNPs) that supported accurate species delimitation, all without the use of a reference genome or annotation data. These sites were used to classify Ictiobus spp. samples with genome-skim data, along with a larger set (n = 67) where ultraconserved elements (UCEs) were sequenced. Analyses of whole mitochondrial data revealed more limited signal. Nearly all samples matched their purported species based on morphologic identification, but two Missouri samples morphologically identified as I. niger grouped with samples of I. bubalus, albeit with significant enrichment of I. niger SNPs. To our knowledge this is the first report of a DNA-based tool to reliably discriminate these three morphologically distinct species.

59 BASIC BIOLOGICAL SCIENCES↗

A 3.4-Å cryo-electron microscopy structure of the human coronavirus spike trimer computationally derived from vitrified NL63 virus particles

Human coronavirus NL63 (HCoV-NL63) is an enveloped pathogen of the family Coronaviridae that spreads worldwide and causes up to 10% of all annual respiratory diseases. HCoV-NL63 is typically associated with mild upper respiratory symptoms in children, elderly and immunocompromised individuals. It has also been shown to cause severe lower respiratory illness. NL63 shares ACE2 as a receptor for viral entry with SARS-CoV-1 and SARS-CoV-2. Here we present the in situ structure of HCoV-NL63 spike (S) trimer at 3.4-Å resolution by single-particle cryo-EM imaging of vitrified virions without chemical fixative. It is structurally homologous to that obtained previously from the biochemically purified ectodomain of HCoV-NL63 S trimer, which displays a 3-fold symmetric trimer in a single conformation. In addition to previously proposed and observed glycosylation sites, our map shows density at other sites, as well as different glycan structures. The domain arrangement within a protomer is strikingly different from that of the SARS-CoV-2 S and may explain their different requirements for activating binding to the receptor. Overall, this structure provides the basis for future studies of spike proteins with receptors, antibodies, or drugs, in the native state of the coronavirus particles.

59 BASIC BIOLOGICAL SCIENCES↗

Mechanisms of Three-Dimensional Solid-Phase Epitaxial Crystallization of Strontium Titanate

Strontium titanate (SrTiO 3 , STO) is a complex metal oxide with a cubic perovskite crystal structure. Due to its easily described and understood crystal structure in the cubic phase, STO is an ideal model system for exploring the mechanistic details of solid-phase epitaxy (SPE) in complex oxides. SPE is a crystallization approach that aims to guide crystal growth at low homologous temperatures to achieve targeted microstructures. Beyond planar thin films, SPE can also exploit the addition of a chemically inert, noncrystallizing, amorphous obstacle in the path of crystallization to generate complex three-dimensional structures. The introduction of this mask fundamentally alters the SPE process, inducing a transition from two- to three-dimensional geometries and from vertical to lateral crystal growth under the influence of the crystal/mask/amorphous boundary. Using a combination of molecular dynamics simulations and experiments, we identify several unique phenomena in the nanoscale growth behaviors in both conventional (unmasked) and masked SPE. Examining conventional SPE of STO, we find that crystallization at the interface is strongly correlated to, and potentially driven by, density fluctuations in the region of the amorphous STO near the crystalline/amorphous interface with a strong facet dependence. In the masked case, we find that the crystalline growth front becomes nonplanar near contact with the mask. We also observe a minimum vertical growth requirement prior to lateral crystallization. Both phenomena depend on the relative bulk and interfacial free energies of the three-phase (crystal/mask/amorphous) system.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Mechanisms of Polyethylene Terephthalate Pellet Fragmentation into Nanoplastics and Assimilable Carbons by Wastewater Comamonas

Comamonadaceae bacteria are enriched on poly(ethylene terephthalate) (PET) microplastics in wastewaters and urban rivers, but the PET-degrading mechanisms remain unclear. Here, we investigated these mechanisms with Comamonas testosteroniKF-1, a wastewater isolate, by combining microscopy, spectroscopy, proteomics, protein modeling, and genetic engineering. Compared to minor dents on PET films, scanning electron microscopy revealed significant fragmentation of PET pellets, resulting in a 3.5-fold increase in the abundance of small nanoparticles (<100 nm) during 30-day cultivation. Infrared spectroscopy captured primarily hydrolytic cleavage in the fragmented pellet particles. Solution analysis further demonstrated double hydrolysis of a PET oligomer, bis(2-hydroxyethyl) terephthalate, to the bioavailable monomer terephthalate. Supplementation with acetate, a common wastewater co-substrate, promoted cell growth and PET fragmentation. Of the multiple hydrolases encoded in the genome, intracellular proteomics detected only one, which was found in both acetate-only and PET-only conditions. Homology modeling of this hydrolase structure illustrated substrate binding analogous to reported PET hydrolases, despite dissimilar sequences. Mutants lacking this hydrolase gene were incapable of PET oligomer hydrolysis and had a 21% decrease in PET fragmentation; re-insertion of the gene restored both functions. Thus, we have identified constitutive production of a key PET-degrading hydrolase in wastewater Comamonas, which could be exploited for plastic bioconversion.

54 ENVIRONMENTAL SCIENCES↗

Electron-Withdrawing meso -Substituents Turn On Magneto-Optical Activity in Porphyrins

A series of square planar metalloporphyrins (M(TPP), TPP is 5,10,15,20-tetraphenylporphyrin and M(TPFPP), TPFPP is 5,10,15,20-tetrapentafluorophenylporphyrin; M is Zn 2+ , Ni 2+ , Pd 2+ , or Pt 2+ ) with distinct meso-substituents were prepared, and their magneto-optical activity (MOA) was characterized by magnetic circular dichroism (MCD) and magneto-optical rotary dispersion spectroscopy (MORD; also known as Faraday rotation spectroscopy). MOA is crucial in the development of next-generation magneto-optical devices and quantum computing. Here, the data show that the presence of meso-pentafluorophenyl substituents results in significant increase in MOA in comparison to the homologous phenyl group. Differences in the MOA of these metalloporphyrins are rationalized using the Gouterman four-orbital model and pave the way for rational design of improved and tailorable magneto-optical materials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Dynamic Profiling of β-Coronavirus 3CL Mpro Protease Ligand-Binding Sites

β-coronavirus (CoVs) alone has been responsible for three major global outbreaks in the 21st century. The current crisis has led to an urgent requirement to develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components are required as a backup against the emergence of lethal viral variants. One such target is the main protease (Mpro) that plays an indispensable role in viral replication. The availability of over 270 Mpro X-ray structures in complex with inhibitors provides unique insights into ligand–protein interactions. Herein, we provide a comprehensive comparison of all nonredundant ligand-binding sites available for SARS-CoV2, SARS-CoV, and MERS-CoV Mpro. Extensive adaptive sampling has been used to investigate structural conservation of ligand-binding sites using Markov state models (MSMs) and compare conformational dynamics employing convolutional variational auto-encoder-based deep learning. Our results indicate that not all ligand-binding sites are dynamically conserved despite high sequence and structural conservation across β-CoV homologs. This highlights the complexity in targeting all three Mpro enzymes with a single pan inhibitor.

59 BASIC BIOLOGICAL SCIENCES↗

Two-Dimensional Energy Histograms as Features for Machine Learning to Predict Adsorption in Diverse Nanoporous Materials

A major obstacle for machine learning (ML) in chemical science is the lack of physically informed feature representations that provide both accurate prediction and easy interpretability of the ML model. In this work, we describe adsorption systems using novel two-dimensional energy histogram (2D-EH) features, which are obtained from the probe-adsorbent energies and energy gradients at grid points located throughout the adsorbent. The 2D-EH features encode both energetic and structural information of the material and lead to highly accurate ML models (coefficient of determination R2 ~ 0.94–0.99) for predicting single-component adsorption capacity in metal–organic frameworks (MOFs). Here, we consider the adsorption of spherical molecules (Kr and Xe), linear alkanes with a wide range of aspect ratios (ethane, propane, n-butane, and n-hexane), and a branched alkane (2,2-dimethylbutane) over a wide range of temperatures and pressures. The interpretable 2D-EH features enable the ML model to learn the basic physics of adsorption in pores from the training data. We show that these MOF-data-trained ML models are transferrable to different families of amorphous nanoporous materials. We also identify several adsorption systems where capillary condensation occurs, and ML predictions are more challenging. Nevertheless, our 2D-EH features still outperform structural features including those derived from persistent homology. The novel 2D-EH features may help accelerate the discovery and design of advanced nanoporous materials using ML for gas storage and separation in the future.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

RTx-303, an Orally Bioavailable Polθ Polymerase Inhibitor That Potentiates PARP Inhibitors in BRCA Mutant Tumors

Abstract DNA polymerase θ (Polθ) is a polymerase-helicase fusion protein that is synthetically lethal with homologous recombination (HR) factors, such as BRCA1/2, and confers resistance to PARP inhibitors (PARPi) and other genotoxic cancer therapies. Previously developed Polθ polymerase (Polθ-pol) inhibitors (Polθi) exhibited limited pharmacological activity and metabolic stability, warranting the development of a Polθi with improved drug-like properties. Here, we developed RTx-303, a selective allosteric small-molecule Polθ-pol inhibitor that exhibits 5.1 nM IC50, 88% oral bioavailability, and a prolonged half-life along with its equipotent metabolite. X-ray crystallography highlights the development of a solvent-exposed side-chain that is essential for the optimal drug-like properties of RTx-303. Notably, RTx-303 exhibits significantly higher cellular potency than previously developed Polθ-pol inhibitors and strongly potentiates PARPi in BRCA1/2 mutant cells and patient-derived xenograft models. The superior potency, robust pharmacological activity, and high tolerability of RTx-303 warrant further development as a Polθ-pol inhibitor drug candidate.

Chandramouly, Gurushankar [Thomas Jefferson Univer↗

Confirmation of PNNL Quantitative Infrared Cross-Sections for Isobutane

The Pacific Northwest National Laboratory (PNNL) gas-phase database is a compilation of quantitative experimental (5, 25, 50 °C) infrared spectra of ca. 500 molecules, designed for in situ, standoff or remote sensing of gases and vapors at or near atmospheric pressure. The data are characterized by calibration on both the wavenumber and intensity axes. Recent papers have called into question the PNNL intensity values for isobutane, (2-methylpropane, HC(CH 3 ) 3 ) suggesting discrepancies of 30 to 40%. In this study we re-measure and re-examine the intensity values of isobutane using both similar and alternate methods to those used to generate the original PNNL database spectra. Here, indirect confirmation from literature data of homologous molecules and direct confirmation from new results confirm that for many band integrals across the isobutane spectrum, the original PNNL data are indeed accurate to within the reported 3% experimental uncertainty.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Amphiphile Organization in Organic Solutions: An Alternative Explanation for Small-Angle X-ray Scattering Features in Malonamide/Alkane Mixtures

In this work, the role of different intermolecular interactions in the aggregation of amphiphiles in an organic solvent is studied for systems of relevance to liquid-liquid extraction (LLE), a chemical process used to selectively recover metals from complex mixtures. Of specific interest is the role, or lack thereof, of hydrogen bonding, which is often assumed to be a main driver of the organic phase structural organization that has been linked to separation efficacy. Toward that end, a series of malonamide extractants in n-dodecane have been studied in the absence of any extracted aqueous solutes, including water. The series of extractants includes N,N'-dimethyl-N,N'-dibutyltetradecylmalonamide (DMDBTDMA), two of its homologs, and N,N'-dimethyl-N,N'-dioctylhexylethoxymalonamide (DMDOHEMA). This simplified model LLE system enables systematic investigation of the role of dipole-dipole and alkyl tail steric interactions in amphiphile aggregation. Small-angle X-ray scattering (SAXS) profiles computed from molecular dynamics trajectories are in good agreement with experimental SAXS data. Molecular dynamics simulations show that malonamide aggregation results from dipole-driven self-association and lacks characteristic aggregate sizes. Mid-q correlation peaks in the SAXS profiles emerge at high concentration for each malonamide. In those densely packed solutions, the correlation peaks are observed to result from alkyl tail-induced spacing between electron-rich polar head groups, with peak positions determined by the different alkyl tail lengths present in the malonamide molecule. This explanation of the SAXS correlation peaks contrasts with the prevailing literature, which attributes mesoscale features observed in small-angle scattering to the formation of microemulsions. Instead, this work finds that these features are present in the absence of water or any reverse micellar organization of the malonamides. As such, molecular-scale malonamide self-association and packing, rather than microemulsion-based colloidal-scale descriptions, is a more appropriate framework for these LLE systems.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Active-Site Environmental Factors Customize the Photophysics of Photoenzymatic Old Yellow Enzymes

The development of non-natural photoenzymatic systems has reinvigorated the study of photoinduced electron transfer (ET) within protein active sites, providing new and unique platforms for understanding how biological environments affect photochemical processes. Here, we use ultrafast spectroscopy to compare the photoinduced electron transfer in known photoenzymes. 12-Oxophytodienoate reductase 1 (OPR1) is compared to Old Yellow Enzyme 1 (OYE1) and morphinone reductase (MR). The latter enzymes are structurally homologous to OPR1. We find that slight differences in the amino acid composition of the active sites of these proteins determine their distinct electron-transfer dynamics. Our work suggests that the inside of a protein active site is a complex/heterogeneous dielectric network where genetically programmed heterogeneity near the site of biological ET can significantly affect the presence and lifetime of various intermediate states. Our work motivates additional tunability of Old Yellow Enzyme active-site reorganization energy and electron-transfer energetics that could be leveraged for photoenzymatic redox approaches.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Screening Ionic Liquids Based on Ionic Volume and Electrostatic Potential Analyses

Ionic liquids are known to have tunable solvation properties, based on the pairing of different anions and cations, but the compositional landscape is vast and challenging to navigate efficiently. Some computational screening protocols are available, but they can be either time-consuming or difficult to implement. Herein, we perform a detailed investigation of the fundamental role of electrostatic interactions in these systems. We effectively develop a bridge between the previous volume-based approach (VBA) with a quantum structure–property relationship (QSPR) approach to create fast, simple screening guidelines. We propose a new parameter that is applicable to both monovalent and multivalent ions, the ionic polarity index (IPI), which is defined as the ratio of the average electrostatic surface potential ($\bar{V}$) of the ion to the net charge of the ion (q). The IPI correlation has been tested on a diverse dataset of 121 ions and reliable predictions can be obtained within a homologous series of ionic liquid compounds.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Solubility Behavior of CO 2 in Ionic Liquids Based on Ionic Polarity Index Analyses

Ionic liquids (ILs) can serve as effective CO 2 solvents with an appropriate selection of different anions and cations. However, due to the large library of potential IL compositions, rapid screening methods are needed for characterizing and ranking the expected properties. We have recently proposed the ionic polarity index (IPI) parameter, effectively connecting volume-based approaches and electrostatic potential analyses, providing a single metric that can potentially be used to rapidly screen for desirable IL properties. In this work, the corresponding anion and cation IPIs are used to generate correlations with respect to the CO 2 volumetric solubility in ILs. The relationships are generally applicable to groups of ILs within a homologous ion series, and this can be particularly valuable for pre-screening different ion pairings for maximizing gas solvation performance.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Observation of [VCu1–Ini2+VCu1–] Defect Triplets in Cu-Deficient CuInS2

Copper indium disulfide (CuInS2) is a semiconductor with a direct energy band gap of 1.53 eV, an optimal value for highly efficient thin-film solar cells. But it has reached only ~ 11 % power conversion efficiency, far less than the theoretically achievable value of ~ 30 %. The cause of this low performance is not understood. A single crystal grown from 1 mol% Cu-deficient melt was studied, using atomic resolution high-angle annular dark-field (HAADF) scanning transmission electron microscopy (STEM) and electron dispersive spectroscopy (EDS). While the bulk crystal is exactly stoichiometric CuInS2, it contains nanometer-thick, structurally coherent, Cu-deficient interphases that form along rotational twin boundaries in the {112} plane. Transition zones from bulk crystal to interphase are observed, where In is seen to move from its normal site InIn in the chalcopyrite structure to a tetrahedral interstitial site Ini, while Cu remains in its normal CuCu position. Two InIn rows of the bulk crystal merge into one row of Ini, causing excess Ini in the interphase. The concentrations of CuCu and Ini reflect a ratio of Cu vacancies, VCu, to excess Ini of ~ 2. Their relative lattice positions, and the high electrical resistivity of the crystal, suggests that VCu and excess Ini ‘precipitate’ as self-compensating, electrically neutral, [VCu1- Ini2+ VCu1-] defect triplets. This is the first atomic-level observation of the ordered defect that has been invoked as the basic structural modifier in chalcopyrite compound homologs. The interphases introduce an optical gap of 1.47 eV. Electron trapping in band tail states, evident from a photoconductivity exponent of 0.54, is the likely cause of an unusually low electron mobility of 0.1 cm2V-1s-1. The overall result is that making CuInS2 slightly copper-poor inserts nanometer-thick layers of the interphase into the bulk crystal. This study shows that apparently conflicting results of the effect of Cu deficiency on CuInS2 thin-film solar cells may be resolved by analyzing structure and composition at nanometer spatial resolution.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Polyelectrolyte Complex Coacervation across a Broad Range of Charge Densities

Polyelectrolyte complex coacervates of homologous (co)polyelectrolytes with a near-ideally random distribution of a charged and neutral ethylene oxide comonomer were synthesized. The unique platform provided by these building blocks enabled an investigation of the phase behavior across charge fractions 0.10 ≤ f ≤ 1.0. Experimental phase diagrams for f = 0.30–1.0 were obtained from thermogravimetric analysis of complex and supernatant phases and contrasted with molecular dynamics simulations and theoretical scaling laws. At intermediate to high f, a dependence of polymer weight fraction in the salt-free coacervate phase (w P,c ) of w P,c ~ f 0.37±0.01 was extracted; this trend was in good agreement with accompanying simulation predictions. Below f = 0.50, w P,c was found to decrease more dramatically, qualitatively in line with theory and simulations predicting an exponent of 2/3 at f ≤ 0.25. Preferential salt partitioning to either coacervate or supernatant was found to be dictated by the chemistry of the constituent (co)polyelectrolytes.

36 MATERIALS SCIENCE↗

Modifying Frank–Kasper Mesophases by Modulating Chain Configuration in PDMS- b -PTFEA Copolymers

The common spherical mesophases observed from chemically distinct compounds have promoted extensive studies of packing structures in soft-matter self-assemblies. In this report we present a new approach for controlling sphere-packing phases by modulating homologous copolymer chain configurations. To this end, three sets of sample pairs, compositionally asymmetric polydimethylsiloxane-b-poly(2,2,2-trifluoroethyl acrylate) (PDMS-b-PTFEA) diblock copolymers (diBCPs) and their homologues containing the corresponding triblock copolymer (triBCP), are synthesized via atom transfer radical polymerization and designed with the consistent volume fractions of the core-forming PTFEA block, f PTFEA = 0.20, 0.18, and 0.15. We identify the formation of C15 and hexagonally close-packed (HCP) phases in the triBCP-containing PDMS-b-PTFEAs, whereas the sigma and C14 phases are formed in their diBCP analogues, respectively. These phase shifts into C15 and HCP, due to molecular configuration differences, reveal a significant yet unrealized role of chain configurations and the associated chain size effects in determining the stable sphere-packing phases in BCP systems.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Bottom-Up Simulation, Reconstruction, and Quantification of Macromolecule Sequences from Experimental Polymerizations

Motivated by the canonical sequence–structure–function paradigm, tools to characterize chemical patterning in natural biomacromolecules, from proteins to nucleic acids, have grown exponentially in recent years. However, analogous strategies for synthetic macromolecules remain in nascent stages, complicated by sequence polydispersity and analytical limitations. To address this, we have developed a comprehensive and open-source Python package, PRISM (polymer rate insights and sequence modeling), an end-to-end workflow that provides a path from experimental kinetics measurements to quantitative and qualitative metrics for describing chemical patterning in stochastic polymers. First, a numerical integration strategy was constructed to simulate and fit experimental data from reversible addition–fragmentation chain transfer (RAFT) polymerization kinetics, enabling the facile estimation of relevant reactivity ratios. These ratios were then used in a mechanism-specific stochastic kinetic simulation strategy to simulate sequence ensembles corresponding to model systems spanning experimental copolymers, classes of statistical polymers (e.g., alternating, block, and gradient), and multiblock copolymers. Lastly, inspired by sequence homology metrics from bioinformatics, we introduce visualization strategies and quantitative metrics to facilitate comparisons of different sequence ensembles. As the sequence–structure–function paradigm becomes increasingly central in de novo design of synthetic macromolecules, this toolkit provides a first step toward accurate and representative sequence description and featurization.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗