A5092774114- Synthesis and Characterization of Heterocyclic Compounds
- Click Chemistry and Applications
- Molecular spectroscopy and chirality
- Fermentation and Sensory Analysis
- Computational Drug Discovery Methods
- X-ray Diffraction in Crystallography
- Energetic Materials and Combustion
- Supramolecular Chemistry and Complexes
Texas Christian University
2023-2025
Differing in pseudoatom, three macrocycles with isosteric substitutions (geminal dimethyl, cyclopropyl, cyclobutyl) can be described as choreoisosteres. Under ambient conditions, they share a dynamic hinge-like motion that fully revolute solution. The barriers to hinging, ΔG‡, are identical within experimental error: ΔG‡ = 14.2–15.2 kcal/mol judged by variable-temperature 13C NMR spectroscopy. Consistent conserved behavior and isosterism, other physical properties including hydrophobicity...
The molecular structures of an anhydrous and dihydrate forms a 24-atom triazine macrocycle containing proline methine hydrazine residues, were determined by MicroED (Single Crystal Electron Diffraction, ScED, 3DED). whole powder pattern profile decomposition (WPPD) Pawley refinement the X-ray Powder Pattern (RT, XRPD) confirms two crystalline in sample indicates one or more additional unidentified states. is protonated at triazines (pKa ∼6) trifluoroacetic acid (TFA, pKa 0.25) to yield...
Modifying the backbone of 24-atom macrocycles allows tailoring physical properties (octanol-water partition coefficients, logP) while conserving both conformation and barrier to dynamic, hinge-like motion. The can be...
Octanol/water partition coefficients guide drug design, but algorithms do not always accurately predict these values. For cationic triazine macrocycles that adopt a conserved folded shape in solution, common fall short. Here, the logD values for 12 differing amino acid choice were predicted and then measured experimentally. On average, AlogP, XlogP, ChemAxon predictions deviate by 0.9, 2.8, 3.9 log units, with XlogP overestimating lipophilicity AlogP underestimating lipophilicity....