DFT study of 2D graphitic carbon nitride based preferential targeted delivery of levosimendan, a cardiovascular drug

Abstract

2D nanocarriers particularly graphitic carbon nitride (g-C3N4) have shown its momentum in nanomedicine to augment the efficacy and safety of pharmaceutical drugs owing to its excellent compatibility and nontoxic nature. In current study, DFT/TD-DFT evaluation is performed for a cardiovascular drug levosimendan, g-C3N4 carrier and their complex g-C3N4-levosimendan at CAMB3LYP/6-31G (++) ** with a high precision of 0.1 eV in charge transfer. To study the nature of the complex different parameters such as non-covalent interaction analysis, density of states, charge decomposition analysis, natural bonding orbital analysis, electrostatic potential and UV-Visible spectra are investigated. The BSSE corrected adsorption energy of complex has confirmed an exothermic reaction indicating successful adsorption of levosimendan on g-C3N4 while solvation energy has described a good solubility index and stability for the complex. All the chemical reactivity parameters indicate a favorable complex having a potential of preferential targeting to the heart tissue. Dipole moment shows a significant increase for complex indicating its high solubility in water while NBO studies has signified the more pronounced interactions where the E value is larger for levosimendan and g-C3N4 which is further supported by ELF and ESP plots. Moreover, less distortion of bonds has been seen with +1 and -1 charges on the surface of g-C3N4-levosimendan-complex. PET based on electron-hole theory specifies g-C3N4 as a chelator while levosimendan as a fluorophore in the g-C3N4-levosimendan complex (also confirmed by UV-Visible results). All the results are in a good support of the complex which signify that g-C3N4 offers an excellent route of administration for levosimendan and has a potential to spark active research in nanomedicine particularly in targeted drug delivery systems.