Design, synthesis, structural analysis and quantum chemical insight into the molecular structure of coumarin derivatives

Seven novel coumarin derivatives were synthesized and the selection of suitable functional groups does the tailoring of the supramolecular synthons. The theoretical studies substantiated the structural analysis results.

A Proline-Based Tectons and Supramolecular Synthons for Drug Design 2.0: A Case Study of ACEI

Proline is a unique, endogenous amino acid, prevalent in proteins and essential for living organisms. It is appreciated as a tecton for the rational design of new bio-active substances. Herein, we present a short overview of the subject. We analyzed 2366 proline-derived structures deposited in the Cambridge Structure Database, with emphasis on the angiotensin-converting enzyme inhibitors. The latter are the first-line antihypertensive and cardiological drugs. Their side effects prompt a search for improved pharmaceuticals. Characterization of tectons (molecular building blocks) and the resulting supramolecular synthons (patterns of intermolecular interactions) involving proline derivatives, as presented in this study, may be useful for in silico molecular docking and macromolecular modeling studies. The DFT, Hirshfeld surface and energy framework methods gave considerable insight into the nature of close inter-contacts and supramolecular topology. Substituents of proline entity are important for the formation and cooperation of synthons. Tectonic subunits contain proline moieties characterized by diverse ionization states: -N and -COOH(-COO−), -N+ and -COOH(-COO−), -NH and -COOH(-COO−), -NH+ and -COOH(-COO−), and -NH2+ and -COOH(-COO−). Furthermore, pharmacological profiles of ACE inhibitors and their impurities were determined via an in silico approach. The above data were used to develop comprehensive classification, which may be useful in further drug design studies.

Evaluation of fluorine-mediated intermolecular interactions in tetrafluorinated tetrahydroisoquinoline derivatives: synthesis and computational studies

Intermolecular interactions involving the aromatic C—F group in the absence of other strong hydrogen bond acceptors is the theme of this article. Weak interactions involving fluorine are known to generate various supramolecular synthons, thereby altering the crystal structures of small organic molecules. It is demonstrated that the weak interactions involving organic fluorine play a major role in directing crystal packing of highly flexible organic molecules like diphenyl tetrahydroisoquinolines reported herein. The intramolecular C—H...F hydrogen bonds are found to be significant in controlling the molecular conformation in specific cases wheras the intermolecular interactions involving the C—F groups result in a wide range of supramolecular synthons involving C—H...F and C—F...F—C interactions. The interactions are studied computationally to provide insight into their energies and the topology of the interactions is studied using Atoms in Molecules. C—H...F—C interactions are found to be quite stabilizing in nature with the stabilization energy of −13.9 kcal mol−1.

Chimeric supramolecular synthons in Ph2Te2(I2)Se

Iodination of Ph2Te2Se by molecular iodine is directed towards the Te atom and yields {diiodo[(phenyltellanyl)selanyl]-λ4-tellanyl}benzene, PhTeSeTeI2Ph or C12H10I2SeTe2. The molecule can be considered as a chimera of PhTeSeR, PhTeSeTePh and R′TeI2Ph fragments. The crystal structure features a complex interplay of the supramolecular synthons Te...π(Ph), Se...Te and I...Te, combining molecules into a three-dimensional framework. Their combination affords long-range supramolecular synthons which are fused in a way resembling the mythological chimera and could be defined as chimeric supramolecular synthons. The energies of the intermolecular interactions have also been calculated and analyzed.

Chirality-dependent supramolecular synthons based on the 1,3-oxazolidin-2-one framework: chiral drugs mephenoxalone, metaxalone and 114 other examples

Analysis of the 119 crystal structures of 1,3-oxazolidin-2-one derivatives, including the chiral muscle relaxants mephenoxalone and metaxalone, showed that cyclic motifs dominate in racemic, and linear in single-enantiomeric, samples.

‘Sacrificial’ supramolecular assembly and pressure-induced polymerization: toward sequence-defined functionalized nanothreads

Supramolecular synthons are exploited to synthesize –OH functionalized sp3-rich sequence-defined nanothreads using pressure-induced polymerization of a phenol:pentafluorophenol co-crystal.