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.
Highlights
Radioligand binding techniques are extensively used to explore biological proteins involved in the pathophysiology of neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease [1,2,3].Neuroprotective targets, including the neuronal nitric oxide synthase enzyme [4], theN-methyl-D -aspartate (NMDA) receptor [3], and voltage gated calcium channels (VGCC) [5] have been widely studied using radioligands
The use of alternative approaches, such as fluorescent methods, to study enzyme-ligand and receptor-ligand binding interactions can provide information that may not be readily available using conventional radiopharmacology techniques, and can avoid some of the disadvantages associated with radiopharmacology, such as high costs, health hazards, disposal, and possible methodological implications [6,7,8,9]
The crystal packing is not planar and has an inversion-related a number of weak C-H· · · π interactions between the adamantane and the isoindole moieties of the molecularconstituting arrangement
Summary
Radioligand binding techniques are extensively used to explore biological proteins involved in the pathophysiology of neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease [1,2,3]. 2 ofthe perform docking experiments to elucidate potential biological binding interactions, and further explore its fluorescent properties. These studies nNOS enzyme, NMDA receptor, and/or VGCC that can be used to develop binding affinity studies will provide valuable information that may be used to develop fluorescent displacement assays using fluorescent displacement assays. These studies compound invaluable an excellent yield in ofthat This is a significant its crystal structure andinformation geometry both the solid and10free-form state, analyze frontier molecular will provide beonly used tomin develop fluorescent displacement assays improvement in yield and reduction in reaction time compared to the conventional method orbitals atomic net utilizingand compound.
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