Multicomponent Crystal of Metformin and Barbital: Design, Crystal Structure Analysis and Characterization.

Xiaoshu Guan,Xiangnan Hu,Li Zhang,Linhong Cai,Cong Li,Lan Jiang

doi:10.3390/molecules26144377

Abstract

The formation of most multicomponent crystals relies on the interaction of hydrogen bonds between the components, so rational crystal design based on the expected hydrogen-bonded supramolecular synthons was employed to establish supramolecular compounds with desirable properties. This theory was put into practice for metformin to participate in more therapeutic fields to search for a fast and simple approach for the screening of candidate crystal co-formers. The prediction of intermolecular synthons facilitated the successful synthesis of a new multicomponent crystal of metformin (Met) and barbital (Bar) through an anion exchange reaction and cooling crystallization method. The single crystal X-ray diffraction analysis demonstrated the hydrogen bond-based ureide/ureide and guanidine/ureide synthons were responsible for the self-assembly of the primary structural motif and extended into infinite supramolecular heterocatemeric structures.

Highlights

The pharmacokinetics show that Met can rap3 iodfly14 arrive at the peak concentration in the cerebrospinal fluid and hippocampus crossing blood–brain barriers within 30 min; it has received a lot of attention in terms of decreasing tshoeropxtiiodnati(vDeVsStr)ewssaosfctohnedburacitnedantod mneeuarsounrael tahpeopmtoosisistuinrepsaotirepnttisonwibtehhnaevuiorordoefgmenuelrtaictiovme,apffoencetinvtec, raynsdtamls.etabolic diseases [5,6]
Twoassugmemnearraitzeed, .thTeorsautimonmaalrdizees,igthneorfatthioisnaml udle-tisciogmn poof ntheinstmcruylsttiacol mbapsoendeonnt csruypsrtalmboalseecduloanr ssyunptrhaomnoalencaulylasrissywnotrhkoendavnearlyyswisewll,oarnkded the expected synthons II and III were observed in the crystal structure sustained by a supramolecular heterocatemer
Very well, and the expected synthons II and III were observed in the crystal structure sustained by a supramolecular heterocatemer

Summary

Introduction

By allowing APIs containing guanidino groups to associate with a co-former involving the –(CONHCO)– group, we surmised that guanidino and acylurea moieties would organize supramolecular synthon assemblies formed via N–H···O and N–H···N hydrogen bonds into extended architectures. It was expected, that Met and/or Bar were able to form a homodimer through synthon A and I, respectively, and linked with each other via synthon B or synthon III to form a 1D chain. Dynamic vapor sorption (DVS) was conducted to measure the moisture sorption behavior of multicomponent crystals

Single Crystal X-ray Diffraction Analysis of the Crystal Structure

Characterization of the Crystal Structure

Characterization of the Moisture Sorption Behavior

Materials