Solvation dynamics of tetracyclic irbesartan in water and dichloromethane: Insights from local energy decomposition and ab initio molecular dynamics simulations library of the heterocyclic rings

• Autor: Aazam, Elham S. ; Thomas, Renjith
• Assuntos: AIMD ; LED ; NBO ; NCI ; Solvated energy
• É parte de: Journal of molecular liquids, 2022-04, Vol.352, p.118709, Article 118709
• Descrição: [Display omitted] •We report the structure and conformational dynamics of irbesartan.•Dynamics of interaction with drug- water/DCM in three different positions.•Quantitative interaction study of water and DCM in different pores using EDA.•Solvent dynamics using ab initio molecular dynamics. Solvation energy changes Gibb’s energy when an ion or molecule is transferred from a vacuum to a solvent. Solvation is the attraction and association of molecules of a solvent with molecules or ions of a solute. Irbesartan is an angiotensin II receptor blocker used to treat hypertension and diabetic nephropathy alone or with other drugs. The central theme presented in this manuscript is the effect of explicit solvent on this drug. We optimized the molecules at the DFT/B3LYP cc-pVDZ level for Natural bond orbitals (NBO), noncovalent interactions (NCI), and wavefunction assay. Solvation energy and ab initio molecular dynamics were studied using PBE0-D3/def2-TZVP and energy decomposition analysis at DLPNO-CCSD(T). Fragmentation studies showed that Irbesartan can produce four fragments: biphenylmethan, butyl-, tetrazole, and diazaspironenone. NBO delocalisation energy of the molecule, and solvated complexes are found to be in the order irbesartan-DCM > irbesartan-water > irbesartan (for oxygen) and irbesartan-water > irbeasartan > irbesartan-DCM (at carbon) and irbesartan-DCM > irbesartan > irbesartan-water (at hydrogen). Noncovalent interactions in water and DCM at different pores showed significant interaction as evident from the binding energies. Ab initio molecular dynamics (AIMD) simulations proved that irbesartan-water pores are less stable than irbesartan-DCM. CPCM delivers solvated free energy and non-electrostatic free energy of irbesartan in water.
  
• Editor: Elsevier B.V
  
• Idioma: Inglês