Scholarly Works, Chemistry

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Macromorphological Control of Zr-Based Metal-Organic Frameworks for Hydrolysis of a Nerve Agent Simulant
Gibbons, Bradley; Johnson, Eric M.; Javed, Mohammad Khurram; Yang, Xiaozhou; Morris, Amanda J. (American Chemical Society, 2024-09-18)
Zirconium-based metal-organic frameworks (MOFs) have become one of the most promising materials for the adsorption and destruction of chemical warfare agents. While numerous studies have shown differences in reactivity based on MOF topology and postsynthetic modification, the understanding of how modifying MOF macromorphology is less understood. MOF xerogels demonstrate modified defect levels and larger porosity, which increase the number of and access to potential active sites. Indeed, UiO-66 and NU-901 xerogels display reaction rates 2 and 3 times higher, respectively, for the hydrolysis of DMNP relative to their powder morphologies. Upon recycling, MOF-808 xerogel outperforms MOF-808 powder, previously noted as the fastest Zr6 MOF for hydrolysis of organophosphate nerve agents. The increase in reactivity is largely driven by a higher external surface area and the introduction of mesoporosity to previously microporous materials.
Customizing STEM organogels using PET-RAFT polymerization
Bowman, Zaya; Baker, Jared G.; Hughes, Madeleine J.; Nguyen, Jessica D.; Garcia, Mathew; Tamrat, Nahome; Worch, Joshua C.; Figg, C. Adrian (Royal Society Chemistry, 2024-10-01)
Photoinduced electron/energy transfer (PET) reversible addition-fragmentation chain transfer (RAFT) polymerization results in more uniform polymer networks compared to networks synthesized by thermally initiated RAFT polymerizations. However, how PET-RAFT polymerizations affect molecular weight control and physical properties during parent-to-daughter block copolymer network synthesis is unclear. Herein, we synthesized a structurally tailored and engineered macromolecular (STEM) organogel composed of poly(methyl acrylate) and a degradable crosslinker. Chain extensions on the STEM organogel were performed using PET-RAFT polymerization of either methyl acrylate (MA) or N,N-dimethylacrylamide (DMA) with or without additional crosslinker. We found that physical properties were dependent on monomer composition and crosslinking. The swelling ratios of the diblock networks were similar in DMAc. Conversely, swelling ratios in water increased by 430% for networks extended with MA and 5200% for networks extended with DMA compared to the parent organogels. Rheological analysis showed a tunable modulus from 1000-4000 Pa. However, size exclusion chromatography analysis of the degraded gels revealed that the PET-RAFT polymerization chain extension yielded disperse block copolymers with poor control over the molecular weight. These results indicate that PET-RAFT polymerizations can be used to expand organogel networks to block copolymer networks to modulate physical properties, but control over the chain extension polymerization is lost. Looking forward, this report points to opportunities to gain control over PET-RAFT block copolymer network synthesis via secondary reversible deactivation pathways. PET-RAFT polymerization was used to modify STEM organogels, while degradable linkers enabled the characterization of the resulting block copolymers.
Electrospun Lithium Porous Nanosorbent Fibers for Enhanced Lithium Adsorption and Sustainable Applications
Pan, Yanan; Zhang, Yue; Thompson, Connor; Liu, Guoliang; Zhang, Wencai (American Chemical Society, 2024-09-30)
Electrospun nanosorbent fibers specifically designed for efficient lithium extraction were developed, exhibiting superior physicochemical properties. These fibers were fabricated using a polyacrylonitrile/dimethylformamide matrix, with viscosity and dynamic mechanical analysis showing that optimal interactions were achieved at lower contents of layered double hydroxide. This meticulous adjustment in formulation led to the creation of lithium porous nanosorbent fibers (Li-PNFs-1). Li-PNFs-1 exhibited outstanding mechanical attributes, including a yield stress of 0.09 MPa, a tensile strength of 2.48 MPa, and an elongation at a break of 19.7%. Additionally, they demonstrated pronounced hydrophilicity and hierarchical porous architecture, which greatly favor rapid wetting kinetics and lithium adsorption. Morphologically, they exhibited uniform smoothness with a diameter averaging 546 nm, indicative of orderly crystalline growth and a dense molecular arrangement. X-ray photoelectron spectroscopy and density functional theory using Cambridge Serial Total Energy Package revealed modifications in the spatial and electronic configurations of polyacrylonitrile due to hydrogen bonding, facilitating lithium adsorption capacity up to 13.45 mg/g under optimal conditions. Besides, kinetics and isotherm showed rapid equilibrium within 60 min and confirmed the chemical and selective nature of Li+ uptake. These fibers demonstrated consistent adsorption performance across multiple cycles, highlighting their potential for sustainable use in industrial applications.
Restricted Open-Shell Cluster Mean-Field theory for Strongly Correlated Systems
Bachhar, Arnab; Mayhall, Nicholas J. (American Chemical Society, 2024-10-07)
The cluster-based Mean Field method (cMF) and it is second order perturbative correction was introduced by Jimenez-Hoyos and Scuseria to reduce the cost of modeling strongly correlated systems by dividing an active space up into small clusters, which are individually solved in the mean-field presence of each other. In that work, clusters with unpaired electrons are treated by allowing the alpha and beta orbitals to spin polarize. While that provided significant energetic stabilization, the resulting cMF wave function was spin-contaminated, making it difficult to use as a reference state for spin-pure post-cMF methods. In this work, we propose the Restricted Open-shell cMF (RO-cMF) method, extending the cMF approach to systems with open-shell clusters, while not permitting spin-polarization. While the resulting RO-cMF energies are necessarily higher in energy than the unrestricted orbital cMF, the new RO-cMF provides a simple reference state for post-cMF methods that recover the missing intercluster correlations. We provide a detailed explanation of the method, and report demonstrative calculations of exchange coupling constants for three systems: a di-iron complex, a dichromium complex, and a dimerized organic radical. We also report the first perturbatively corrected RO-cMF-PT2 results as well.
Pin1 WW Domain Ligand Library Synthesized with an Easy Solid-Phase Phosphorylating Reagent
Chen, Xingguo R.; Mercedes-Camacho, Ana Y.; Wilson, Kimberly A.; Bouchard, Jill J.; Peng, Jeffrey W.; Etzkorn, Felicia A. (American Chemical Society, 2024-10-08)
Cell cycle regulatory enzyme Pin1 both catalyzes pSer/Thr-cis/trans-Pro isomerization and binds the same motif separately in its WW domain. To better understand the function of Pin1, a way to separate these activities is needed. An unnatural peptide library, (RCO)-C-1-pSer-Pro-NHR2, was designed to identify ligands specific for the Pin1 WW domain. A new solid-phase phosphorylating reagent (SPPR) containing a phosphoramidite functional group was synthesized in one step from Wang resin. The SPPR was used in the preparation of the library by parallel synthesis. The final 315-member library was screened with our WW-domain-specific, enzyme-linked enzyme-binding assay (ELEBA). Four of the best hits were resynthesized, and the competitive dissociation constants were measured by ELEBA. NMR chemical-shift perturbations (CSP) of ligands with N-15-labeled Pin1 were used to measure K( d )for the best four ligands directly, demonstrating that they were specific Pin1 WW domain ligands. Models of the ligands bound to the Pin1 WW domain were used to visualize the mode of binding in the WW domain.
Catalyzing PET-RAFT Polymerizations Using Inherently Photoactive Zinc Myoglobin
Anderson, Ian C.; Gomez, Darwin C.; Zhang, Meijing; Koehler, Stephen J.; Figg, C. Adrian (Wiley-V C H Verlag, 2025-01-10)
Protein photocatalysts provide a modular platform to access new reaction pathways and affect product outcomes, but their use in polymer synthesis is limited because co-catalysts and/or co-reductants are required to complete catalytic cycles. Herein, we report using zinc myoglobin (ZnMb), an inherently photoactive protein, to mediate photoinduced electron/energy transfer (PET) reversible addition-fragmentation chain transfer (RAFT) polymerizations. Using ZnMb as the sole reagent for catalysis, photomediated polymerizations of N,N-dimethylacrylamide in PBS were achieved with predictable molecular weights, dispersity values approaching 1.1, and high chain-end fidelity. We found that initial apparent rate constants of polymerization increased from 4.6x10-5 s-1 for zinc mesoporpyhrin IX (ZnMIX) to 6.5x10-5 s-1 when ZnMIX was incorporated into myoglobin to yield ZnMb, indicating that the protein binding site enhanced catalytic activity. Chain extension reactions comparing ZnMb-mediated RAFT polymerizations to thermally-initiated RAFT polymerizations showed minimal differences in block copolymer molecular weights and dispersities. This work enables studies to elucidate how protein modifications (e.g., secondary structure folding, site-directed mutagenesis, directed evolution) can be used to modulate polymerization outcomes (e.g., selective monomer additions towards sequence control, tacticity control, molar mass distributions).
"Best" Iterative Coupled-Cluster Triples Model? More Evidence for 3CC
Teke, Nakul K.; Melekamburath, Ajay; Gaudel, Bimal; Valeev, Edward F. (American Chemical Society, 2024-10-31)
To follow up on the unexpectedly good performance of several coupled-cluster models with approximate inclusion of 3-body clusters [ we performed a more complete assessment of the 3CC method [ for accurate computational thermochemistry in the standard HEAT framework. New spin-integrated implementation of the 3CC method applicable to closed- and open-shell systems utilizes a new automated toolchain for derivation, optimization, and evaluation of operator algebra in many-body electronic structure. We found that with a double-zeta basis set the 3CC correlation energies and their atomization energy contributions are almost always more accurate (with respect to the CCSDTQ reference) than the CCSDT model as well as the standard CCSD(T) model. The mean absolute errors in cc-pVDZ {3CC, CCSDT, and CCSD(T)} electronic (per valence electron) and atomization energies relative to the CCSDTQ reference for the HEAT data set [, were {24, 70, 122} mu E h/e and {0.46, 2.00, 2.58} kJ/mol, respectively. The mean absolute errors in the complete-basis-set limit {3CC, CCSDT, and CCSD(T)} atomization energies relative to the HEAT model reference, were {0.52, 2.00, and 1.07} kJ/mol, The significant and systematic reduction of the error by the 3CC method and its lower cost than CCSDT suggests it as a viable candidate for post-CCSD(T) thermochemistry applications, as well as the preferred alternative to CCSDT in general.
Comparative Risk of Developing Interstitial Cystitis with Childhood Gastrointestinal, Urological, Autoimmune, or Psychiatric Disorders
Alipour-Vaezi, Mohammad; McNamara, Robert S.; Rukstalis, Margaret R.; Gentry, Emily C.; Rukstalis, Daniel B.; Penzien, Donald B.; Tsui, Kwok-Leung; Zhong, Huaiyang (Wiley, 2025-09-01)
Aims: Interstitial cystitis (IC) is a chronic urological condition associated with significant discomfort, posing diagnostic and therapeutic challenges. Although its etiology remains unclear, early-life conditions such as gastrointestinal (GI) disorders, urological anomalies (UA), psychiatric disorders (PD), and autoimmune diseases (AD) have been hypothesized as potential risk factors for developing IC in adulthood. This study aims to investigate these associations by conducting a retrospective cohort analysis utilizing data from the TriNetX US Collaborative Network, encompassing over 118 million patient records. Methods: The study and control groups were established across four categories of childhood disorders, with IC incidence monitored over a 14-year period. Statistical methodologies, including propensity score matching and Kaplan-Meier survival analysis, were employed to compare outcomes between cohorts. Results: Findings indicate that childhood GI and UA conditions significantly elevate the risk of IC in adulthood, with irritable bowel syndrome (IBS) and urinary tract infections (UTIs) exhibiting risk ratios of 2.9 and 3.2, respectively. Gender disparities were also noted, with females exhibiting higher incidences of diseases included, particularly UA and AD during adolescence. Additionally, individuals with these early-life conditions demonstrated a higher prevalence of comorbidities, underscoring the complex interplay of health factors contributing to IC pathogenesis. Conclusions: These findings suggest that childhood GI and UA conditions may serve as predictive markers for IC, emphasizing the need for targeted early interventions and preventative care strategies. By identifying at-risk populations, this study provides valuable insights into early detection and management approaches, potentially mitigating the long-term burden of IC on affected individuals. Trial Registration: This paper includes an observational retrospective study. No clinical trial has been conducted.
Stereo- and Enantioselective Syntheses of 1,2-Oxaborinan-3-enes and δ-Boryl-Substituted Homoallylic Alcohols
Zhang, Zheye; Chen, Ming (American Chemical Society, 2024-11-19)
Stereo- and enantioselective syntheses of 1,2-oxaborinan-3-enes and delta-boryl-substituted homoallylic alcohols are reported. We developed a practical approach to synthesize alpha-boryl-substituted allylboronate. This reagent was utilized to generate alpha,alpha-disubstituted allylboronates, and such reagents cannot be accessed via the Pd-catalyzed alkene isomerization approach. Chiral Br & oslash;nsted-acid-catalyzed aldehyde addition with these reagents gave 1,2-oxaborinan-3-enes with excellent stereo- and enantioselectivities. Lewis-acid-catalyzed aldehyde addition also worked well, affording delta-boryl-substituted homoallylic alcohols with high stereoselectivities. The enantioselective variant of the reaction was achieved via a chiral Br & oslash;nsted-acid-catalyzed aldehyde addition and Pd-catalyzed alkene isomerization approach.
Reaction-Type-Dependent Behavior of Redox-Hopping in MOFs-Does Charge Transport Have a Preferred Direction?
Yan, Minliang; Bowman, Zaya; Knepp, Zachary J.; Peterson, Aiden; Fredin, Lisa A.; Morris, Amanda J. (American Chemical Society, 2024-11-21)
Redox hopping is the primary method of electron transport through redox-active metal-organic frameworks (MOFs). While redox hopping adequately supports the electrocatalytic application of MOFs, the fundamental understandings guiding the design of redox hopping MOFs remain nascent. In this study, we probe the rate of electron and hole transport through a singular MOF scaffold to determine whether the properties of the MOF promote the transport of one carrier over the other. A redox center, [RuII(bpy)2(bpy-COOH)]2+, where bpy = 2,2 '-bipyridine and bpy-COOH = 4-carboxy-2,2 '-bipyridine, was anchored within NU-1000. The electron hopping coefficients (D e ) and ion diffusion coefficients (D i ) were calculated via chronoamperometry and application of the Scholz model. We found that electrons transport more rapidly than holes in the studied MOF. Interestingly, the correlation between D e and self-exchange rate built in previous research predicted reversely. The contradicting result indicates that spacing between the molecular moieties involved in a particular hopping process dominates the response.
Polarizable AMOEBA force field predicts thin and dense hydration layer around monosaccharides
Newman, Luke A.; Patton, Mackenzie G.; Rodriguez, Breyanna A.; Sumner, Ethan W.; Welborn, Valerie Vaissier (Royal Society Chemistry, 2024-12-03)
Polarizable force fields crucially enhance the modeling of macromolecules in polar media. Here, we present new parameters to model six common monosaccharides with the polarizable AMOEBA force field. These parameters yield a thinner, but denser, hydration layer than that previously reported. This denser hydration layer results in eliminating non-physical aggregation of glucose in water-an issue that has plagued molecular dynamics simulations of carbohydrates for decades.
Design, Synthesis, and Biological Evaluation of [1,2,5]Oxadiazolo[3,4-b]pyridin-7-ol as Mitochondrial Uncouplers for the Treatment of Obesity and Metabolic Dysfunction-Associated Steatohepatitis
Foutz, Mary A.; Krinos, Emily L.; Beretta, Martina; Hargett, Stefan R.; Shrestha, Riya; Murray, Jacob H.; Duerre, Ethan; Salamoun, Joseph M.; Mccarter, Katrina; Shah, Divya P.; Hoehn, Kyle L.; Santos, Webster L. (American Chemical Society, 2024-11-30)
Mitochondrial uncouplers are small molecule protonophores that act to dissipate the proton motive force independent of adenosine triphosphate (ATP) synthase. Mitochondrial uncouplers such as BAM15 increase respiration and energy expenditure and have potential in treating a variety of metabolic diseases. In this study, we disclose the structure-activity relationship profile of 6-substituted [1,2,5]oxadiazolo[3,4-b]pyridin-7-ol derivatives of BAM15. Utilizing an oxygen consumption rate assay as a measure of increased cellular respiration, SHO1122147 (7m) displayed an EC50 of 3.6 mu M in L6 myoblasts. Pharmacokinetic studies indicated a half-life of 2 h, C max of 35 mu M, and no observed adverse effects at 1,000 mg kg-1 dose in mice. In a Gubra-Amylin (GAN) mouse model of MASH, SHO1122147 was efficacious in decreasing body weight and liver triglyceride levels at 200 mg kg-1 day-1 without changes in body temperature. These findings indicate the potential of utilizing novel [1,2,5]oxadiazolo[3,4-b]pyridin-7-ol mitochondrial uncouplers for treatment of fatty liver disease and obesity.
Gelation during Ring-Opening Reactions of Cellulosics with Cyclic Anhydrides: Phenomena and Mechanisms
Petrova, Stella P.; Zheng, Zhaoxi; Heinze, Daniel Alves; Welborn, Valerie; Bortner, Michael J.; Schmidt-Rohr, Klaus; Edgar, Kevin J. (American Chemical Society, 2024-11-21)
Cellulose esters are used in Food and Drug Administration-approved oral formulations, including in amorphous solid dispersions (ASDs). Some bear substituents with terminal carboxyl moieties (e.g., hydroxypropyl methyl cellulose acetate succinate (HPMCAS)); these omega-carboxy ester substituents enhance interactions with drug molecules in solid and solution phases and enable pH-responsive drug release. However, the synthesis of carboxyl-pendent cellulose esters is challenging, partly due to competing reactions between introduced carboxyl groups and residual hydroxyls on different chains, forming either physically or covalently cross-linked systems. As we explored ring-opening reactions of cyclic anhydrides with cellulose and its esters to prepare polymers designed for high ASD performance, we became concerned upon encountering gelation. Herein, we probe the complexity of such ring-opening reactions in detail, for the first time, utilizing rheometry and solid-state 13C NMR spectroscopy. Gelation in these ring-opening reactions was caused predominantly by physical interactions, progressing in some cases to covalent cross-links over time.
Self-Healing and Stretchable Molecular Ferroelectrics with High Expandability
Wang, Zhongxuan; Yang, Haochen; Zhu, Long; Wang, Qian; Quan, Lina; Chen, Po-Yen; Ren, Shenqiang (Wiley-V C H Verlag, 2025-03-01)
The interplay between crystal ordering and stretchability is frequently encountered in contemporary materials science, particularly in the case of ferroelectrics. The inherent dilemma arises when these materials need to withstand repetitive mechanical deformations or stretching without sacrificing their crystal integrity, all while retaining their remarkable ferroelectric properties and even exhibiting self-healing capabilities. This complexity further presents a significant challenge in the design and engineering of mechanically rigid molecular ferroelectric crystals, particularly for applications where both precise crystalline structure and mechanical adaptability are crucial. In this study, the humidity-controlled expansion and contraction, dissolution, and recrystallization of a self-assembled molecular ferroelectric-in-hydrogel framework are reported. Self-healing ferroelectric-in-hydrogel networks exhibit a recyclable humidity-tailored ionic conductivity from 2.86 x 10-6 to 1.36 x 10-5 S cm-1, facilitating the stretchable piezoelectric sensing. Additionally, the dynamic bond reforming interactions are observed, leading to the tailoring of Young's modulus from 452 to 170 MPa, maintaining ferroelectricity under a strain of 20% with a piezoelectric coefficient of 15.7 pC N-1. Upon lattice contraction, the molecular contacts undergo reforming, leading to the restoration of stretchable ferroelectrics/piezoelectrics and paving the way for stretchable bioelectronics for full-body motion monitoring. The capabilities highlighted here open avenues for stretchable and self-healing ferroelectric-in-hydrogel bioelectronic technologies.
Process parameter optimization in polymer powder bed fusion of final part properties in polyphenylene sulfide through design of experiments
Ho, Ian; Bryant, Jackson; Chatham, Camden; Williams, Christopher (Springernature, 2024-12-17)
The Additive Manufacturing (AM) modality of Laser-Based Powder Bed Fusion of Polymers (PBF-LB/P) is an established method for manufacturing semi-crystalline polymers. Like other AM processes, the selection of PBF-LB/P process parameters is critical as it has direct effect on final part properties. While prior research has been predominantly focused on polyamides (e.g., nylon 12), there exists a gap in exploring how process parameters affect higher performance polymers, such as polyphenylene sulfide (PPS). This work aims to explore the effects of PBF-LB/P process parameters on PPS parts printed via PBF-LB/P. While prior PBF-LB/P parameter research primarily relies on evaluating energy input to the system through a single numerical value of energy density, this study investigates the interplay of the print parameters within the energy density equation. To achieve these goals, an analysis was performed on the influence of the laser power, hatch spacing, and beam velocity on ultimate tensile strength (UTS), modulus, and crystallinity of printed parts. A Taguchi L8 array was used in balancing the print parameter combinations allowing for isolation of variance to the specific factors and interactions. Through this approach, print parameter combinations that improved UTS and modulus were identified. Additionally, the study revealed that numerically equivalent energy densities did not lead to equivalent performance, underscoring the significance for including the constitutive process parameters within the energy density equation when establishing process property relationships in printing with PBF-LB/P.
Highly Active Oligoethylene Glycol Pleuromutilins via Systematic Linker Synthesis/One-Pot Attachment and a Microscale Solubility Method
Breiner, Logan M.; Slowinski, Roman P.; Lowell, Andrew N. (American Chemical Society, 2024-12-18)
The semisynthetic derivatization of natural products is crucial for their continued development as antibiotics. While commercial pleuromutilin derivatives depend on amines for solubility, we demonstrate the high activity and solubility of oligoethylene glycol-substituted pleuromutilins achieved via a one-pot deprotection/attachment approach using thiolates protected as thioesters. The bifunctional linker synthesis is versatile and can be broadly applied to other chemistries. Antibacterial assays revealed this simple glycolate modification enhanced inhibition 4-8-fold relative to that of pleuromutilin. A new microscale solubility method is also introduced.
Copper Oxidation-Induced Nanoscale Deformation of Electromechanical, Laminate Polymer/Graphene Thin Films during Thermal Annealing: Implications for Flexible, Transparent, and Conductive Electrodes
Croft, Zacary L.; Valenzuela, Oscar; Thompson, Connor; Whitfield, Brendan; Betzko, Garrett; Liu, Guoliang (American Chemical Society, 2024-12-12)
The transfer of large-area, continuous, chemical vapor deposition (CVD)-grown graphene without introducing defects remains a challenge for fabricating graphene-based electronics. Polymer thin films are commonly used as supports for transferring graphene, but they typically require thermal annealing before transfer. However, little work has been done to thoroughly investigate how thermal annealing affects the polymer/graphene thin film when directly annealed on the growth substrate. In this work, we demonstrate that under improper annealing conditions, thermal annealing of poly(ether imide)/single-layer graphene (PEI/SLG) thin films on Cu causes detrimental nanoscale structural deformations, which permanently degrade the mechanical properties. Furthermore, we elucidate the mechanisms of PEI/SLG deformation during thermal annealing and find that permanent deformations and cracking are caused by Cu substrate oxidation. This study provides an understanding of annealing-induced deformation in polymer/graphene thin films. We anticipate that this knowledge will be useful for further developing defect-free, graphene-based thin film electronics.
Scaling up the production of fungal perylenequinones and investigating their biosynthesis through stable isotope labeling
Al-Qiam, Reema A.; Dumbare, Sachin; Graf, Tyler N.; Vidar, Warren S.; Raja, Huzefa A.; Pearce, Cedric J.; Hematian, Shabnam; Oberlies, Nicholas H. (2025-10-03)
Background: Perylenequinones, such as hypocrellins and hypomycins, are fungal secondary metabolites with potential for pharmaceutical and industrial applications due to both their physical and biological properties. This study focused on their sustainable production. Additionally, stable isotope labeling was used to probe the biosynthesis of these compounds, demonstrating how sugars are likely incorporated into the perylenequinone scaffold. Methods: Shiraia sp. (strain MSX60519; Shiraiaceae, Pleosporales) was cultivated under varying nutrient conditions to evaluate the production of perylenequinones, with sugars serving as primary carbon sources. Five metabolites were isolated (from oatmeal cultures) using environmentally friendly solvent-based techniques, and the process was further optimized to maximize yields. High-performance liquid chromatography (HPLC) and liquid chromatography–high-resolution mass spectrometry (LC–HRMS) were employed to detect, characterize, and quantify the major compounds. Furthermore, feeding experiments were performed using 13C-labeled glucose, with droplet probe mass spectrometry used to monitor stable isotope incorporation in situ. Results: This study yielded three key findings. First, the production of perylenequinones was significantly enhanced by supplementing fermentation media with sugars, and disaccharides significantly enhanced the production of perylenequinones compared to monosaccharides. Optimizing sugar concentrations during the fermentation further influenced the profile of secondary metabolites. Second, stable isotope labeling experiments confirmed that sugars are the primary building blocks of perylenequinones, as noted by tracing 13C-labeling into ent-shiraiachrome A (1). Finally, a green, scalable, and sustainable strategy for producing these compounds on the gram scale was developed by optimizing fermentation conditions, refining purification methods, and improving extraction efficiency. Conclusion: These findings provide critical insights into optimizing fermentation conditions for the scaled and sustainable production of perylenequinones. This approach offers a cost-effective and environmentally friendly pipeline for harnessing these valuable compounds, paving the way for broader pharmaceutical and industrial applications.
Thermodynamics of calcium binding to heparin: Implications of solvation and water structuring for polysaccharide biofunctions
Knight, Brenna M.; Gallagher, Connor M. B.; Schulz, Michael D.; Edgar, Kevin J.; McNaul, Caylyn D.; McCutchin, Christina A.; Dove, Patricia M. (National Academy of Sciences, 2025-08-26)
Heparin sulfates are found in all animal tissues and have essential roles in living systems. This family of biomacromolecules modulates binding to calcium ions (Ca²⁺) in low free energy reactions that influence biochemical processes from cell signaling and anticoagulant efficacy to biomineralization. Despite their ubiquity, the thermodynamic basis for how heparans and similarly functionalized biomolecules regulate Ca²⁺ interactions is not yet established. Using heparosan (Control) and heparins with different positions of sulfate groups, we quantify how SO₃⁻ and COO⁻ content and SO₃⁻ position modulate Ca²⁺ binding by isothermal titration calorimetry. The free energy of all heparin-Ca²⁺ interactions (ΔGrxn) is dominated by entropic contributions due to favorable water release from polar, hydrophilic groups. Heparin with both sulfate esters (O-SO₃⁻) and sulfamides (N-SO₃⁻) has the strongest binding to Ca²⁺ compared to heparosan and to heparin with only O-SO₃⁻ groups (~3X). By linking Ca²⁺ binding thermodynamics to measurements of the interfacial energy for calcite (CaCO₃) crystallization onto polysaccharides, we show molecule-specific differences in nucleation rate can be explained by differences in water structuring during Ca²⁺ interactions. A large entropic term (-TΔSrxn) upon Ca²⁺–polysaccharide binding correlates with high interfacial energy to CaCO₃ nucleation. Combining our measurements with literature values indicates many Ca²⁺–polysaccharide interactions have a shared thermodynamic signature. The resulting enthalpy–entropy compensation relationship suggests these interactions are generally dominated by water restructuring involving few conformational changes, distinct from Ca²⁺–protein binding. Our findings quantify the thermodynamic origins of heparin-specific interactions with Ca²⁺ and demonstrate the contributions of solvation and functional group position during biomacromolecule-mediated ion regulation.
Broad Host Range Peptide Nucleic Acids Prevent Gram-Negative Biofilms Implicated in Catheter-Associated Urinary Tract Infections
Karp, Hannah Q.; Nowak, Elizabeth S.; Kropp, Gillian A.; Col, Nihan A.; Schulz, Michael D.; Sriranganathan, Nammalwar; Rao, Jayasimha (MDPI, 2025-08-20)
Biofilms develop in sequential steps resulting in the formation of three-dimensional communities of microorganisms that are encased in self-produced extracellular polymeric substances. Biofilms play a key role in device-associated infections, such as catheter-associated urinary tract infections (CAUTIs), because they protect microorganisms from standard antimicrobial therapies. Current strategies to prevent biofilm formation in catheter-related infections, including prophylactic antibiotics and antibiotic-coated catheters, have been unsuccessful. This finding highlights a need for novel approaches to address this clinical problem. In this study, biofilm-forming phenotypes of common Gram-negative bacteria associated with CAUTIs were treated with antisense peptide nucleic acids (PNAs), and biofilm biomass and bacterial viability were quantified after 24 h of treatment. A cocktail of PNAs targeting the global regulator genes rsmA, amrZ, and rpoS in Pseudomonas aeruginosa significantly reduced viability and thus appropriately eliminated biofilm biomass. Antisense-PNAs against these same gene targets and the motility regulator gene motA inhibited biofilm formation among isolates of Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli but did not reduce bacterial viability. These results suggest that antisense-PNAs are a promising new technology in preventing biofilm formation in urinary catheters, especially as a potential complement to conventional antimicrobials.

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