Rodrigo Antonio Cormanich

We benchmark the effect of the geometry optimization in B3LYP, PBE0 and M06L calculations of indirect nuclear spin–spin coupling constants in 13 electron correlation-rich small molecules against high-level CC3 reference values from a previous study.

We benchmark the DFT functionals B3LYP, PBE0, and M06L for calculating 45 indirect nuclear spin-spin coupling constants (SSCCs) in 13 electron correlation-rich small molecules, using high-level CC3 reference values from a previous study. The dataset spans a wide variety of one-, two-, and three-bond couplings, enabling a systematic assessment of functional performance and the impact of geometry optimization on SSCC calculations. Overall, PBE0 combined with PBE0-optimized geometries provides the closest match to CC3 results, followed by M06L at B3LYP or M06L geometries. A strong functional dependence is observed for fluorine-containing couplings: M06L markedly outperforms PBE0 and B3LYP for these, especially for one-bond C-F couplings, whereas PBE0 is clearly superior for couplings not involving fluorine. Across all molecules, the geometry-optimization method has a significant influence on the resulting SSCCs, and the best performance is consistently achieved when the same method is used for both geometry optimization and SSCC computation. In contrast, CCSD(T) geometries systematically yield the poorest agreement with CC3 SSCCs when combined with any of the three DFT functionals.

Spectroscopic phenomena like the Perlin effect ( ¹ J _CH coupling constants) and the Bohlmann effect (C–H IR stretching) reveal quantum processes such as hyperconjugation and help assess the conformational properties of compounds.

New synthesis approaches and properties of the tris -fluoromethylated motif are explored relative to tert -butyl, in the context of medicinal chemistry.

Bicyclo[1.1.0]butane (BCB) is a highly strained framework whose reactivity arises from the predominant p-character of its central C-C bond. Using density functional theory (DFT) and Natural Bond Orbital (NBO) analysis,...

Polymeric materials capable of releasing nitric oxide (NO) locally have potential uses in various biomedical applications. One of the main challenges in this field is obtaining materials that allow the modulation of NO release rates through the incorporation of different NO donor molecules. Herein, we describe the synthesis of materials composed of poly(2-hydroxyethyl methacrylate) (PHEMA) crosslinked by a polysilsesquioxane (PSS) network through sol–gel polymerization and photocrosslinking. Increasing the PSS content from 5 to 20 wt% led to an increase in the glass transition temperature from 107 °C to 133 °C. Swelling studies in phosphate buffer saline solution and ethanol revealed that higher siloxane content reduced the solvent uptake of the hybrids, while surface contact angle measurements confirmed that all compositions remained hydrophilic (60–70°). These hybrids enabled, for the first time, the incorporation of two structurally distinct NO donors, hydrophilic S-nitrosoglutathione (GSNO) and hydrophobic S-nitroso-N-acetyl-DL-penicillamine (SNAP), via absorption from aqueous and ethanolic solutions, respectively. Computational modeling showed that GSNO forms multiple hydrogen bonds with PHEMA hydroxyl groups, while SNAP interacts hydrophobically with its methyl groups. Real-time NO measurements showed that SNAP spontaneously releases NO at a flow rate 2 to 10 times higher than that of GSNO in the first 30 min after hydration of the hybrids, likely due to its weaker intermolecular interactions and higher mobility upon hydration. The hydrophilic nature of the hybrids, tunable NO release, and lack of cytotoxicity toward cultured endothelial cells position them as promising candidates for the manufacturing of antithrombotic blood-contacting medical devices.

The RCH ₂ F and RCHF ₂ groups are substituents of interest in medicinal and agrochemicals products. They have a polar aspect relative to the methyl (RCH ₃ ) or trifluoromethyl (RCF ₃ ) groups which results in a lowering of Log P's (water affinity). Here we use a computational approach to explore the nature of the interaction between RCH ₂ F and RCHF ₂ in methanes and ethanes with chloride ion (and water), as a hydrogen bonding acceptor. A key observation is that the hydrogen atoms geminal to the fluorine(s) become less positively charged with increasing fluorination, a trend anticipated to weaken, not strengthen, their hydrogen bonding interactions. However this study demonstrates a dominating role for the electrostatic interaction of the acceptor with the CF carbons and profiles a shift in negative charge density from hydrogen to the carbon and fluorine(s) as chloride ion (or water) approach. The common occurrence of blue shifts (shortening C─H length) in these ‘improper’ or ‘non‐classical’ hydrogen bonds is also explored and is correlated with the electrostatic interactions between the acceptor and the carbon atoms. These observations are extended to C ₃ ─C ₆ alicyclic rings containing these motifs and predict particularly strong interactions energies between chloride ion and specifically designed organo‐fluoro alicycles.

Compound protocols of DFT and GFN-xTB methods provide cost-efficient and accurate tools for computational modelling of Janus-face cyclohexane systems.