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 synthesised using an optimised microwave irradiation reaction and crystallised 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 showed that the optimised geometry is similar to the crystal structure parameters with a root-mean-squared deviation of 0.143 Å. 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 analysed. Important binding interactions between the DFT optimised structure and amino acids within the nNOS active site were identified that explain 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 values of 336 nm and 380 nm, respectively.

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 minimization 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 minutes using a desk Hermle Z 100 M ® Microfuge and the supernatant was discarded.…”