A5029167485- Advanced NMR Techniques and Applications
- Atomic and Subatomic Physics Research
- Electron Spin Resonance Studies
- Crystallization and Solubility Studies
- Adenosine and Purinergic Signaling
- NMR spectroscopy and applications
- Solid-state spectroscopy and crystallography
- X-ray Diffraction in Crystallography
- Molecular spectroscopy and chirality
- DNA and Nucleic Acid Chemistry
- Porphyrin Metabolism and Disorders
- Amino Acid Enzymes and Metabolism
- Microbial Natural Products and Biosynthesis
- Advanced biosensing and bioanalysis techniques
- Folate and B Vitamins Research
- Spectroscopy and Quantum Chemical Studies
- Chemical Synthesis and Analysis
- RNA and protein synthesis mechanisms
- Mass Spectrometry Techniques and Applications
- Synthesis and Biological Evaluation
- Drug Transport and Resistance Mechanisms
- Pancreatic function and diabetes
- Renal Transplantation Outcomes and Treatments
University of Tennessee at Knoxville
2022-2025
Southern Illinois University Carbondale
2018-2023
Herein, we demonstrate "direct" 13 C hyperpolarization of C-acetate via signal amplification by reversible exchange (SABRE). The standard SABRE homogeneous catalyst [Ir-IMes; [IrCl(COD)(IMes)], (IMes=1,3-bis(2,4,6-trimethylphenyl), imidazole-2-ylidene; COD=cyclooctadiene)] was first activated in the presence an auxiliary substrate (pyridine) alcohol. Following addition sodium 1-13 C-acetate, parahydrogen bubbling within a microtesla magnetic field (i.e. under conditions shield enables...
The self-association of metabolites into well-ordered assemblies at the nanoscale has significant biological and medical implications. thiol-containing amino acid cysteine (CYS) can assemble amyloid-like nanofibrils, its oxidized form, disulfide-bonded cystine (CTE), forms hexagonal crystals as those found in cystinuria due to metabolic disorder. Yet, there have been no attempts connect these two phenomena, especially fibril-to-crystal transition. Here, we reveal that are not separated...
Conformational flexibility allows macrocyclic peptides like cyclosporine A (CycA) to cross membranes, yet drug design leveraging this property has largely failed. key challenge is linking specific conformers function, as different govern permeability versus target binding. We reveal a mechanism that enhances CycA and alisporivir (ALI) permeability: trans-to-cis isomerization at MeVal11-MeBmt1 creates remain "soluble" in both membrane-like aqueous environments. biased equilibrium favors...
Our study reveals the underlying principles governing passive membrane permeability in three large N-methylated macrocyclic peptides (N-MeMPs): cyclosporine A (CycA), Alisporivir (ALI), and H (CycH). We determine a series of conformers required for robust diffusion those relevant to other functions, such as binding protein targets or intermediates, presence solvent additives. investigate conformational interconversions establish correlations with permeability. Nuclear magnetic resonance...
An atomic view of a main aqueous conformation cyclosporine A (CycA), an important 11-amino-acid macrocyclic immunosuppressant, is reported. For decades, it has been grand challenge to determine the free CycA in aqueous-like solution given its poor water solubility. Using combination X-ray and single-crystal neutron diffraction, we unambiguously resolve unique conformer (A1) with novel cis-amide between residues 11 1 two ligands that stabilize hydrogen bond networks. NMR spectroscopy...
Abstract Herein, we demonstrate “direct” 13 C hyperpolarization of C‐acetate via signal amplification by reversible exchange (SABRE). The standard SABRE homogeneous catalyst [Ir‐IMes; [IrCl(COD)(IMes)], (IMes=1,3‐bis(2,4,6‐trimethylphenyl), imidazole‐2‐ylidene; COD=cyclooctadiene)] was first activated in the presence an auxiliary substrate (pyridine) alcohol. Following addition sodium 1‐ C‐acetate, parahydrogen bubbling within a microtesla magnetic field (i.e. under conditions shield enables...
The present work investigates the potential for enhancing NMR signals of DNA nucleobases by parahydrogen-based hyperpolarization. Signal amplification reversible exchange (SABRE) and SABRE in Shield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) selected is demonstrated with enhancement (ε) 1H, 15N, and/or 13C spins 3-methyladenine, cytosine, 6-O-guanine. Solutions standard homogenous catalyst Ir(1,5-cyclooctadeine)(1,3-bis(2,4,6-trimethylphenyl)imidazolium)Cl (“IrIMes”) a given...
We show the simultaneous generation of hyperpolarized 13 C-labeled acetate and 15 N-labeled imidazole following spin-relay hyperpolarization hydrolysis acetyl moiety on 1-13 C-15 N2 -acetylimidazole. Using SABRE-SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei), transfer spin order occurs from parahydrogen acetylimidazole N atoms C site (≈263-fold enhancement), giving rise relatively long lifetimes at 0.3 T (T1 ≈52 s ≈149 for N,...
Beauvericin (BEA) and enniatins (ENN) are cyclic hexadepsipeptide mycotoxins known for their ionophoric activities across cell membranes. While ability to selectively bind alkali ions form binary complexes has been studied, interaction with multivalent metal higher-order remains less explored. We report the unique characteristics of 1:2, Mn+:BEA or ENN monovalent, divalent, trivalent ions. A thorough IMS-MS analysis underscores substantial interplay among ionic radii, coordination numbers,...
Nuclear magnetic resonance (NMR) spectroscopy of small molecules protonated in a solvent-free environment was successfully demonstrated. The method is referred to as protonation NMR (SoF-NMR). Leveraging matrix-assisted ionization (MAI), we generated species aniline, 4-chloroaniline, 4-aminobiphenyl, and benzocaine for analysis under mild pressure temperature conditions. SoF-NMR spectra were compared traditional solution spectra, the shift changes nuclear spin frequencies verify that these...