A REVIEW ON SUPRAMOLECULAR CHEMISTRY IN DRUG DESIGN AND FORMULATION RESEARCH

Supramolecular chemistry, other way called as intermolecular chemistry disclose the relationship of molecules with environment. It exploits while exposing the physicochemical phenomina that happens when two like or unlike molecules/ions/systems contact each other. Drug action involve the target recognition process and response triggered by the intermolecular complex of drug and target. Drug design therefore require in depth study of intermolecular forces that exist between drug and target. Formulation of the drug or Active Pharmaceutical Ingredient (API) is also regulated by these forces. Compatibility and incompatibility in formulations are nothing but of the effect of the intermolecular forces on physical behavior of systems. Therefore review of intermolecular chemistry in general and its role particularly in pharmaceutical research is presented here for the benefit of the students and research scholars who aspire to work on interdisciplinary projects in the field of pharmacy. Key words: intermolecular forces, hydrogen bond, drug design, active pharmaceutical ingredient (API), crystal

Synthesis, characterization and molecular modelling of a novel dipyridamole supramolecule – X-ray structure, quantum mechanics and molecular dynamics study to comprehend the hydrogen bond structure–activity relationship

Hydrochloride salt formation for Active Pharmaceutical Ingredients (APIs) is the primary choice to impart aqueous solubility and to promote dissolution. Dipyridamole (DIP) is a cardiovascular drug which is practically insoluble in water. We discovered a new form of DIP called as dipyridamole hydrochloride trihydrate (DIPHT), which was prepared by an unusual method of reacting the DIP with hydrated hydrochloric acid (HCl) that was liberated in situ by the reaction of ferric chloride with water. The liberated HCl was consumed as reagent in situ by the scavenger (API) and was converted to a hydrochloride trihydrate. The product was characterized by FTIR, mass spectroscopy, PXRD and DSC. Supramolecular structure of this novel DIPHT was revealed by single crystal XRD. A sustained intramolecular hydrogen bond alliance was found in DIP and the DIPHT. Stability of this hydrogen bond was further evaluated by means of molecular modelling studies. We performed electron calculations using quantum mechanics (QM) on both the base and salt structures to compare their geometry and molecular orbital energy levels. Molecular Dynamics (MD) simulations were also conducted in explicit solvent models to provide more insights into the hydrogen bond strength and conformational preferences of the base and salt structure. Together with QM and MD, we were able to explain the influence of hydrogen bonds on proton uptake activity of DIP and stability of DIP and DIPHT. DIPHT which can dissolve faster than DIP in water may enhance the dissolution and bioavailability of the drug. As the current drug development research is shifting to repurpose the existing drugs in order to subside the untoward risks in new drug development, we believe that DIPHT with its intrinsic aqueous solubility could bring more application for DIP and generate interest within the pharmaceutical industry

A REVIEW ON SUPRAMOLECULAR CHEMISTRY IN DRUG DESIGN AND FORMULATION RESEARCH

Supramolecular chemistry, other way called as intermolecular chemistry disclose the relationship of molecules with environment. It exploits while exposing the physicochemical phenomina that happens when two like or unlike molecules/ions/systems contact each other. Drug action involve the target recognition process and response triggered by the intermolecular complex of drug and target. Drug design therefore require in depth study of intermolecular forces that exist between drug and target. Formulation of the drug or Active Pharmaceutical Ingredient (API) is also regulated by these forces. Compatibility and incompatibility in formulations are nothing but of the effect of the intermolecular forces on physical behavior of systems. Therefore review of intermolecular chemistry in general and its role particularly in pharmaceutical research is presented here for the benefit of the students and research scholars who aspire to work on interdisciplinary projects in the field of pharmacy

Induced Fit Docking (IFD) study of the Solid State Structure of (2E)-1-(5- bromothiophen-2-yl)-3- [4- (dimethylamino) phenyl]prop-2-en-1-one – fragment based design approach for human aldose reductase inhibition

Solid state structure information for (2E)-1-(5-bromothiophen-2-yl)-3-[4-(dimethylamino)phenyl]prop-2-en-1- one is revealed by using single crystal X-ray diffraction study. The conformation of the molecule in solid state is used to carry out the drug design studies like structure optimization by Density Functional Theory (DFT) and Induced Fit Docking (IFD) study on human aldose reductase. The asymmetric unit of (2E)-1-(5-bromothiophen-2-yl)-3-[4- (dimethylamino) phenyl]prop-2-en-1-one, C15H14Br N O S, contains just one molecule. The crystal structure displays intermolecular C11---H11...O3 & C17---H17...O3 hydrogen bonds. Docking experiments were conducted for the crystal structure conformation inside AR active site using Maestro 9.1v. from Schrödinger Suite 2009. GLIDE scoring function was used to calculate the dock score. The co-crystallized inhibitor (IDD594) in X-ray structure of AR-inhibitor complex (PDB id: 1USO) was taken as reference to correlate the results. In docking study the molecule has shown good binding capacity with a dock score of - 9.53891. The negative score for docking experiment signifies favorable positioning of ligand inside AR active site and the value is comparable to that of reference substrate (-10.6841). Results suggested that the molecule can be used as starting point for the development of human aldose reductase inhibitor in fragment based design

(2E)-3-(2-Bromophenyl)-1-(5-bromothiophen-2-yl)prop-2-en-1-one

The asymmetric unit of the title compound, C13H8Br2OS, contains two molecules, in which the dihedral angles between the thiophene and benzene rings are 10.5 (3) and 33.2 (4)°. There are no significant directional interactions in the crystal