Synthesis, Crystal Structure, DFT Studies, Docking Studies, and Fluorescent Properties of 2-(Adamantan-1-yl)-2H-isoindole-1-carbonitrile

Abstract

2-(Adamantan-1-yl)-2H-isoindole-1-carbonitrile (1) has been identified as a neurobiological fluorescent ligand that may be used to develop receptor and enzyme binding affinity assays. Compound 1 was synthesized using an optimized microwave irradiation reaction, and crystallized from ethanol. Crystallization occurred in the orthorhombic space group P212121 with unit cell parameters: a = 6.4487(12) Å, b = 13.648(3) Å, c = 16.571(3) Å, V = 1458(5) Å3, Z = 4. Density functional theory (DFT) (B3LYP/6-311++G (d,p)) calculations of 1 were carried out. Results indicated that the optimized geometry was similar to the experimental results, with a root-mean-squared deviation of 0.143 Å. In this paper, frontier molecular orbital energies and net atomic charges are discussed with a focus on potential biological interactions. Docking experiments within the active site of the neuronal nitric oxide synthase (nNOS) protein crystal structure were carried out and analyzed. Important binding interactions between the DFT-optimized structure and amino acids within the nNOS active site were identified that explained the strong NOS binding affinity reported. Fluorescent properties of 1 were studied using aprotic solvents of different polarities. Compound 1 showed the highest fluorescence intensity in polar solvents, with excitation and emission maximum values of 336 nm and 380 nm, respectively.

Density functional theory studies on graphene/h-boron nitride hybrid nanosheets for supercapacitor electrode applications

“…The slight variation in the atomic radii and electronegativity of individual B, C, and N atoms resulted in the minimal deviation of average bond length and average bond angle. Though the deviation in the average bond length and bond angle of the optimized structure is minimum, the overall accuracy of the structural calculation can be verified by performing root mean squared deviation (RMSD) calculation 62 using PyMol 2.3.2 63 and is listed in Table 2.…”

Structural Analysis, Molecular Modelling and Preliminary Competition Binding Studies of AM-DAN as a NMDA Receptor PCP-Site Fluorescent Ligand

“…: 5UOW [9]). The methods used are similar to those originally reported by Joubert et al, 2018 and 2019 [27,28], with the exception of the protein used for the docking experiments. The Molecular Operating Environment (MOE) 2018 software suite [23] was used for docking studies with the following protocol: (i) the enzyme protein structure was checked for missing atoms, bonds, and contacts, (ii) removal of water molecules, 3D protonation and energy minimisation was done with parameters, force field: MMFF94X+solvation, gradient: 0.05, chiral constraint and current geometry.…”

“…Final DMSO concentrations were kept lower than 2%. A 100 μL solution of 0.55 mM NMDA/glycine solution was then added to selectively stimulate the opening of the NMDAR channel [1,2,27]. After incubation of 5 min at 37 °C the cellular suspension was centrifuged for 2 min using a desk Hermle Z 100 M ® Microfuge and the supernatant was discarded.…”

Crystal structure, Hirshfeld surface analysis and DFT studies of 5-(adamantan-1-yl)-3-[(4-chlorobenzyl)sulfanyl]-4-methyl-4H-1,2,4-triazole, a potential 11β-HSD1 inhibitor

“…A crystal unit within the crystal structure of the 4 was selected as the starting structure for the DFT calculations. Structural optimization was performed using the Gaussian09 program package 31 , in the same manner as previously reported by our group 26 . Energy minima calculations were carried out using the Becke’s three parameters Lee-Yang-Parr exchange correlation functional (B3LYP).…”

“…: 4C7J). The docking method employed is similar to that reported by our group for studies on protease- and neuronal nitric oxide synthase enzymes 26,53 . The Molecular Operating Environment (MOE) 2018 software suite 41 was used for docking studies with the following protocol.…”