Hydrogen Bonds of C=S, C=Se and C=Te with C-H in Small-Organic Molecule Compounds Derived from the Cambridge Structural Database (CSD)

Considerable interest in hydrogen bonding involving chalcogen has been growing since the IUPAC committee has redefined hydrogen bonding. Not only the focus is on unconventional acceptors, but also on donors not discussed before. It has been mentioned in previous studies that the proton of the H-C group could be involved in hydrogen bonding, but with conventional acceptors. In this study, we explored the ability of hydrogen bond formation of Se, S and Te acceptors with the H-C donor using Cambridge Structural Database in conjunction with Ab Initio calculations. In the CSD, there are respectively 256, 6249 and 11 R1,R2,-C=Se, R1,R2,-C=S and R1,R2,-C=Te structures that form hydrogen bonds, in which the N,N groups are majority. Except for C=S acceptor which can form a hydrogen bond with its C, C group, both C=Se and C=Te acceptors could form a hydrogen bond only with N,C and N,N groups. CSD analysis shows very similar d (norm) around -0.04 Å, while DFT-calculated interaction for N,C and N,N groups are also similar. Both interaction distances derived from CSD analysis and DFT-calculated interaction energies demonstrate that the acceptors form stable complexes with H-CF3. Besides hydrogen bonds, dispersion interactions are forces stabilizing the complexes since their contribution can reach 50%. Analysis of intra-molecular geometries and Ab Initio partial charges show that this bonding stems from resonance induced Cδ+=Xδ- dipoles. In many respects, both C=Se, C=S and C=Te are similar to C=S, with similar d (norm) and calculated interaction strengths.

Chalcogen Bonds in Small-Organic Molecule Compounds Derived from the Cambridge Structural Database (CSD)

Growing interest in non-covalent interactions involving chalcogen atoms has been ascribed to their importance in crystal engineering, molecular recognition and macromolecular edifices. The present study is dealing with chalcogen bonds involving divalent Sulphur, Selenium and Tellurium atoms, acting as sigma-hole donors, in small-molecule compounds using the Cambridge Structural Database (CSD) in conjunction with ab initio calculations. Results derived from CSD surveys and computational study revealed that nucleophiles formed complexes with the chalcogen-bond donors R1-X-R2 (X = S, Se or Te). The main forces stabilizing the complexes were chalcogen bonds, enhanced by dispersion interactions. Complexation pattern and energetics show that nucleophile bonding at divalent S, Se and Te atoms is a relatively strong and directed interaction. The bond consists of a charge transfer from a nucleophile atom lone pair to an X-R1 or X-R2 antibonding orbital.

Docking of Human Heat Shock Protein 90 with Selenoderivatives of Geldanamycin

The interference of human heat shock protein 90 (HSP90) in many signalling networks associated with cancer progression makes it an important drug target. In the present work, we investigated the binding ability of 9 selenoderivatives of geldanamycin (GMDSe) at the N-terminal domain of HSP90 derived from Protein Data Bank (PDB code: 1YET) based on ligand-protein docking. All selenoderivatives interacted positively with HSP90, yet the binding strength decreased when replacing monovalent oxygen in position 1 (GMDSe1) or 9 (GMDSe9). Hydrogen-bonding and lipophilic interactions between selenoderivatives and amino acid residues in the inhibitor site of HSP90 were thermodynamically the main forces driving the binding stability. Molecular electrostatic potential surfaces of the selenoderivatives showed marked non polar areas, which were probably involved in the lipophilic interactions with the hydrophobic residues of amino acids. Interestingly, the amino acid residues forming the hydrogen bonds with GMD were also involved in the hydrogen-bonding interactions with the selenoderivatives. Moreover, HSP90 interacted with the GMDSe6 and GMDSe7 selenoderivatives stronger than with GMD, while maintaining lipophilic interactions and hydrogen bonds with amino acid residues like Asp93, which are catalytically crucial for therapeutic properties of HSP90 inhibitors. This finding should guide further studies of pharmacophore properties of GMD selenoderivatives in order to explore their therapeutic properties. It is noteworthy that selenium has been suggested to reduce the risk of various types of cancers.

Interaction of Iron(III)-5,10,15,20-Tetrakis (4-Sulfonatophenyl) Porphyrin with Chloroquine, Quinine and Quinidine

Iron(III)-5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (FeTPPS) is used as non-physiological metalloporphyrin model for the natural iron (III)-protoporphyrin IX (FePPIX) resulting from hemoglobin degradation to investigate ligand binding reactions in aqueous solution. Studies were conducted on the interaction of FeTPPS with Chloroquine, Quinine, and Quinidine, which are historically the most common quinoline-based drugs used to treat malaria, an infectious disease afflicting several hundred millions every year worldwide, mainly in tropical regions. Using UV-Visible spectrophotometry, the binding reaction was studied at pH 7.40 in purely aqueous solution, and in aqueous solution containing NaNO3 at concentration of 0.1 M. Fitted titration curves obtained were in agreement with experimental data according to a formation scheme of 1:1 complex (1 FeTPPS μ-oxo-dimer: 1 Antimalarial). Values of apparent binding constant (K) obtained were between 4.3 × 103 M-1 to 7.59 × 104 M-1, demonstrating that FeTPPS and the antimalarials formed stable complexes. The stability of the complex decreased when NaNO3 was added to the solution. This ionic strength dependence was ascribed to electrostatic effects. Quinine and Chloroquine interacted with FeTPPS stronger than Quinidine did. Chloroquine showed the strongest affinity to FeTPPS. These findings revealed the influence of steric and stereochemical factors. Molecular electrostatic potentials (MEP) calculated with Hartree-Fock theory argue in favor of π-π and electrostatic interactions between reaction partners as driving forces for the complex formation. In the case of FeTPPS: Chloroquine interaction, it is suggested that an intramolecular hydrogen bond is formed between phenyl??and quinuclidine N-H+ as additional force stabilizing the complex. Analysis of crystallographic data using the Cambridge Structural Database (CSD) gave evidence of the hydrogen bond formation between phenyl??and N-H+ groups in 370 structures.

Docking of Glycokinase with Oxo, Sulfo, and Seleno Derivatives of the Carboxamide Activator S41

Inactivation of Glucokinase (GK) is associated with diabetes. Therefore, design of drugs targeting the GK activator site is currently integrated in the?strategy of the diabetes treatment.?The present work investigated the affinity of 30 ligands to GK based on molecular docking using the Gold 5.6 program. Glucokinase’s structure was derived from the Protein Data Bank (PDB Code?3S41), while the ligands were seleno, sulfo and oxo derivatives of the co-crystallized?carboxamide activator (PDB code:?S41). The results of the ligand-protein docking?revealed that GK formed thermodynamically stable complexes with all ligands. The main forces stabilizing the complexes are lipophilic interactions, enhanced by hydrogen bonds. Ligand molecular areas responsible for lipophilic and hydrogen bonding contacts with amino acid residues in the allosteric site of GK were evidenced by molecular electrostatic potentials (MEPs). Interestingly,?twelve of the S41 derivatives interacted with GK more strongly than the co-crystallized activator, while maintaining the lipophilic contacts with key amino acid residues like Arg63, which are catalytically crucial for?therapeutic properties of GK activators (GKAs).?It is noteworthy that divalent Se and S atoms were also involved in chalcogen bonds in the GKA site. Those bonds were nearly linear like hydrogen bonds. Such bond directionality should guide the design of pharmacophoric ligands containing chalcogen atoms.