Crystallographic and DFT Studies on Pyrrolo[1,2-c]imidazole Scaffolds

The crystal structures of the compounds C15H14N4O2 (1) and C16H16N4O4 (2) are reported and analyzed by single crystal X-ray diffraction technique. Compounds (1) and (2) crystallized in monoclinic space group P21/c and Cc with four molecules in the unit cell, respectively. The unit cell parameters for compound (1) are = 11.4501(15) ？, = 9.7869(11) ？, = 12.3653(15) ？, β = 90.997(11)°, and Volume = 1385.5(3) ？3 and for compound (2) are = 13.865(2) ？, = 6.9538(8) ？, = 16.841(2) ？, β = 98.602(11)°, and Volume = 1605.4(4) ？3. In both compounds (1) and (2), the pyrrolidine ring adopts half-chair conformation. Moreover, both inter- and intramolecular N–H？O hydrogen bonds stabilize the crystal structure and play a crucial role in crystal packing. This intermolecular interaction alone constructs chain motif in both compounds. It is also supported by weak intermolecular π-π interaction which is essential for the stability of the crystal packing. Further, the Density Functional Theory (B3LYP) method with standard 6-31G basis set was used in the calculation and calculated geometrical parameter is correlated with the corresponding experimental data. The obtained HOMO and LUMO energies are in negative values indicating that the compounds are in stable state. 1. Introduction The five-membered heterocyclic pyrrolidine ring system commonly occurs in many natural products and these five members are leading components of alkaloids [1]. They are essential synthetic components of HIV reverse transcriptase enzyme and inhibitors of substance P neurotransmitters [2, 3]. Further, they also act as antibacterial and antiamnestic agents [4, 5]. The heterocyclic imidazole derivatives are also considered to be an important synthetic precursor in drug designing and discovery process [6, 7]. These imidazole derivatives have antitumor, antimicrobial, and anti-inflammatory activity and they also inhibit MAP kinase p38 protein [8]. Also, the novel Py-Im derivatives have been established as powerful partial agonists of the 1A adrenoceptor (GPCR known as adrenergic receptor) and have shown better response over the 1B, 1D, and 2A receptor subtypes [9]. The fused Py-Im derivative also inhibits the JNK (c-Jun-N-terminal kinase) pathway which is the fascinating drug target for several neurodegenerative disorders. In view of the growing biological importance of Py-Im derivatives, the single crystal X-ray diffraction studies on the compounds were carried out and analyzed. 2. Experimental 2.1. Synthesis Synthesis of