Ingrid Jelemenska

Four benzyltrimethylammonium (BTMA) salts were successfully prepared: bis(benzyltrimethylammonium) hexachloroplatinate (1), benzyltrimethylammonium tetrachloroaurate (2), bis(benzyltrimethylammonium) tetrachlorocuprate (3), and bis(benzyltrimethylammonium) tetrabromocuprate (4) from benzyltrimethylammonium hydroxide (Triton B). Their crystal structures were determined by single-crystal X-ray diffraction, and the supramolecular architectures were characterized hierarchically. Extended Hirshfeld surface analysis, including enrichment ratio calculations, was performed to evaluate intermolecular interactions. Nonclassical hydrogen bonds, such as C–H^…Cl(Br), involving the anions, contribute to the formation of self-assembled architectures. Additional stabilization arises from π^…π and Cu–Br^…π interactions, particularly in crystals 2 and 4, respectively. Hirshfeld surface analysis showed that H^…H and C^…H/H^…C interactions are the dominant contributors in all crystals. According to enrichment ratio calculations, C^…H/H^…C interactions in 1, 3, and 4; Cl^…H/H^…Cl in 1 and 3; Cu^…H/H^…Cu in 3 and 4; and Br^…H/H^…Br and Br^…C/C^…Br in 4 are statistically favored in the crystal packing. Halogen bonding Cl^…Cl was observed in 1 but does not significantly influence packing. Energy framework calculations indicated that dispersive interactions are favorable in the analyzed crystals. A library of H-bonding supramolecular patterns, including interchangeable synthons, is provided and may guide the rational design of new derivatives with controllable features. Finally, the topology of intermolecular connections and the electronic structure of the benzyltrimethylammonium cation, investigated by quantum-chemical calculations, provide insights into its reactivity.

This study presents the synthesis and comprehensive characterization of a novel, modified ultra-short peptide, Ac-Phe-Aib-Deg-OH ( N -acetyl- L -phenylalanyl-α-aminoisobutyryl - α,α-diethylglycine), ( 1 ), highlighting its potential as an anticancer ligand for G protein-coupled receptors (GPCRs). The structure of the compound was elucidated using single-crystal X-ray crystallography, revealing its pseudo-macrocyclic nature. Hydrogen bonds and dispersion forces drive the hierarchical supramolecular self-assembly of ( 1 ). A comparative analysis with structurally similar structures, that is, achatin derived from the Cambridge Structural Database, was conducted using diverse in silico methods. A detailed analysis of intra- and intermolecular interactions in the structures, especially using modern structural database-driven techniques, provides further insight into the preferential bonding mode of ( 1 ) as a potential drug candidate. Density functional theory calculations were performed to rationalize the interactions and reactivity of the molecules. To validate the predicted anticancer activity of the analysed molecules, we evaluated the binding affinities of these molecules to cancer-related GPCRs. We examined the interaction maps using molecular docking analysis with targets associated with various types of cancer. These findings suggest that ( 1 ) could be a promising candidate for future studies on designing innovative pseudo-macrocyclic ultra-short peptides containing unnatural amino acids for new targeted anticancer therapy.

The experimental electron density distributions in two coordination compounds – one with a central Cu(I) atom and the other with Cu(II), coordinated by the same biphenyldiimino dithioether (bite) type of ligand – have been obtained from high-resolution X-ray reflection data to model the possible electron predisposition for the redox reaction in blue copper proteins. The bite ligand has been adapted to the conformation required by the central atom.

The anti-inflammatory, antiviral, and anti-cancer properties, as well as the mechanism of action of cyclo-[Pro-Pro-β³-HoPhe-Phe-] tetrapeptide (denoted as 4B8M), were recently described. The aim of this work was to synthesize and evaluate the immunosuppressive actions of the stereochemical variants of 4B8M by sequential substitution of L-amino acids by D-amino acids (a series of peptides denoted as P01–P07) using parent 4B8M as a reference compound. In addition, diverse available bioinformatics tools using machine learning and artificial intelligence were tested to find the bio-pharmacokinetic and polypharmacological attributes of analyzed stereomers. All peptides were non-toxic to human peripheral blood mononuclear cells (PBMCs) and only cyclo-[D-Pro-Pro-β³-HoPhe-Phe-] peptide (P03) was capable of inhibiting mitogen-induced PBMC proliferation. The peptides inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) to various degrees, with P04 (cyclo-[Pro-Pro-D-β³-HoPhe-Phe-]) and P03 being the most potent. For further in vivo studies, P03 was selected because it had the combined properties of inhibiting cell proliferation and TNF-α production. P03 demonstrated a comparable ability to 4B8M in the inhibition of auricle edema and lymph node cell number and in the normalization of a distorted blood cell composition in contact sensitivity to the oxazolone mouse model. In the mouse model of carrageenan-induced inflammation of the air pouch, P03 exhibited a similar inhibition of the cell number in the air pouches as 4B8M, but its inhibitory effects on the percentage of neutrophils and eosinophils in the air pouches and blood, as well as on mastocyte degranulation in the air pouches, were stronger in comparison to 4B8M. Lastly, in a mouse model of dextran sulfate-induced colitis, similar effects to 4B8M regarding thymocyte number restoration and normalization of the blood cell pictures by P03 were observed. In summary, depending on either experimental findings or in silico predictions, P03 demonstrated comparable, or even better, anti-inflammatory and bio-pharmacokinetic properties to 4B8M and may be considered as a potential therapeutic. The possibility of P00 and P03 identification by circular dichroism measurements was tested by quantum-chemical calculations.

The anti (a) to syn (s) isomerization pathway of the deprotonated form of the dimer with two nickel(II) 15-membered octaazamacrocyclic units connected via a carbon–carbon (C–C) σ bond was investigated. For the initial anti (a) structure, a deprotonation of one of the bridging (sp³ hybridized) carbon atoms is suggested to allow for an a to s geometry twist. A 360° scan around the bridging C–C dihedral angle was performed first to find an intermediate geometry. Subsequently, the isomerization pathway was explored via individual steps using a series of mode redundant geometry optimizations (internal coordinates potential energy surface scans) and geometry relaxations leading to the s structure. The prominent geometries (intermediates) of the isomerization pathway are chosen and compared to the a and s structures, and geometry relaxations of the protonated forms of selected intermediates are considered.

The anti (a) to syn (s) isomerization pathway of the deprotonated form of the carbon-carbon (C-C) σ dimer complex with two nickel(II) 15-membered octaazamacrocyclic units was investigated. For the initial anti (a) structure, a deprotonation of one of the bridging (sp³ hybridized) carbon atoms is suggested to allow for an a to s geometry twist. A 360° scan around the bridging C-C dihedral angle was performed first to find an intermediate geometry. Subsequently, the isomerization pathway was explored via individual steps using a series of mode redundant geometry optimizations and geometry relaxations leading to the s structure. The prominent geometries (intermediates) of the isomerization pathway are chosen and compared to the a and s structures. Finally, geometry relaxations of the protonated forms of selected intermediates are considered. It is shown that albeit the reaction barrier appears to be higher than that obtained in the experiment, the DFT series of mode redundant geometry optimizations and geometry relaxations proves itself useful in the exploration of the isomerization pathway of the chosen diastereomeric dinickel(II) bis(octaazamacrocyclic) complex.

The experimental electron density distribution in two coordination compounds, one with a central atom Cu(I) and the other with Cu(II), coordinated by the same biphenyldiimino dithioether-type ligand (bite) has been obtained from high-resolution X-ray diffraction data to model the possible electron predisposition for the redox reaction in blue copper proteins. The bite ligand has been adapted to the conformation required by the central atom

The purpose of this review is to highlight how the antioxidant effectiveness (AE) of rubber additives can be quantitatively interpreted using results from quantum‐chemical calculations. The relationships between the AE of para‐phenylene diamines (PPD), evaluated through non‐isothermal differential scanning calorimetry measurements in styrene‐butadiene and polyisoprene rubber matrices, and various parameters obtained by quantum‐chemical calculations are reviewed. The N atom between both phenyl rings (A site) is more significant than the N atom between the phenyl ring and the alkyl chain (B site). The preferred formation of ketimine structures (instead of the quinonediimine ones) during dehydrogenation despite the higher stability of the N _A ‐centered radicals indicates a kinetic control of the antioxidant action. In most cases, the AE decreases with the strength of the N _A –H _A bond and increases with the chemical shifts of N _A and H _A . In hypothetical Cu(II) complexes, the AE rises with the affinity of N _A to Cu, and the extent of electron density transfer from N _A to Cu. Most deviations from linearity might be explained by steric hindrances. Reverse trends for the N _A and N _B chemical shifts are observed, despite the fact that similar reactions are supposed at both sites.

High-resolution X-ray diffraction experiments, theoretical calculations and atom-specific X-ray absorption experiments were used to investigate two nickel complexes, (MePh ₃ P) ₂ [Ni ^II (bdtCl ₂ ) ₂ ]·2(CH ₃ ) ₂ SO [complex (1)] and (MePh ₃ P)[Ni ^III (bdtCl ₂ ) ₂ ] [complex (2)]. Combining the techniques of nickel K - and sulfur K -edge X-ray absorption spectroscopy with high-resolution X-ray charge density modeling, together with theoretical calculations, the actual oxidation states of the central Ni atoms in these two complexes are investigated. Ni ions in two complexes are clearly in different oxidation states: the Ni ion of complex (1) is formally Ni ^II ; that of complex (2) should be formally Ni ^III , yet it is best described as a combination of Ni ²⁺ and Ni ³⁺ , due to the involvement of the non-innocent ligand in the Ni— L bond. A detailed description of Ni—S bond character (σ,π) is presented.

Two 15-membered octaazamacrocyclic nickel(II) complexes are investigated by theoretical methods to shed light on their affinity forwards binding and reducing CO₂. In the first complex ¹[Ni^IIL]⁰, the octaazamacrocyclic ligand is grossly unsaturated (π-conjugated), while in the second ¹[Ni^IILH]²⁺ one, the macrocycle is saturated with hydrogens. One and two-electron reductions are described using Mulliken population analysis, quantum theory of atoms in molecules, localized orbitals, and domain averaged fermi holes, including the characterization of the Ni-C_CO2 bond and the oxidation state of the central Ni atom. It was found that in the [NiLH] complex, the central atom is reduced to Ni⁰ and/or Ni^I and is thus able to bind CO₂ via a single σ bond. In addition, the two-electron reduced ³[NiL]²⁻ species also shows an affinity forwards CO₂.