title: Adsorption of Antifungal Drugs Inside Pristine and Functionalized Fullerenes and Nanotubes: DFT Investigation.
abstract: BACKGROUND
  Econazole, sulconazole and tioconazole usage as antifungal agents is limited due to poor pharmacokinetic properties. Pristine and hydroxylated structures of the C240 fullerene and single walled carbon nanotube (SWCNT) were proposed as transporters of these imidazoles potentially enhancing their pharmacokinetics.
  
  
  METHODS
  To assess possibility of creation of the endohedral complexes of the azoles and carbon nanostructures, their adsorption and interaction energies were calculated with the hybrid exchange-correlation density functional B97-1 and 6-31(d,p) basis set. Interactions within the transporter - drug complexes were investigated with the Atoms in Molecules (AIM) Theory and Reduced Density Gradient (RDG).
  
  
  CONCLUSIONS
  The adsorption energies of the studied azoles depend on type and surface modification of the transporter. Hydroxylation of the fullerene and nanotube surface makes an opportunity for chemisorption of the investigated antifungal drugs. The pristine and hydroxylated nanotube complexes exhibit thermodynamic stability. The complexes of the fullerenes are thermodynamically unstable but its kinetic stability could be significant thus allowing for the such structures to exist. The energetic instability would enhance liberation of the encapsulated molecule from the complex. It is advantageous in the context of drug release.
authors.affiliation: Department of Drug Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.|Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097 Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Pieńko
authors.affiliation: Department of Drug Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Grudzień
authors.affiliation: Department of Pharmacodynamics, Center of Preclinical Research and Technology, Faculty of Pharmacy, Medical University of Warsaw, Zwirki i Wigury 81, 02-097 Warsaw, Poland.
authors.forename: Przemysław Paweł
authors.initials: PP
authors.lastname: Taciak
authors.affiliation: Department of Drug Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.|Department of Synthetic Drugs, National Medicines Institute, 30/34 Chelmska, 00-725 Warsaw, Poland.
authors.forename: Aleksander P
authors.initials: AP
authors.lastname: Mazurek
mesh_terms: D000327:Adsorption; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004464:Econazole / Q000008:administration & dosage* / Q000737:chemistry; D037741:Fullerenes / Q000737:chemistry*; D007093:Imidazoles / Q000008:administration & dosage* / Q000737:chemistry; D008958:Models, Molecular; D037742:Nanotubes, Carbon / Q000737:chemistry*; D011789:Quantum Theory; D012995:Solubility; D013816:Thermodynamics
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D037741:Fullerenes; D007093:Imidazoles; D037742:Nanotubes, Carbon; C530172:pristine (C60); C033308:sulconazole; D004464:Econazole; C020527:tioconazole
keywords: Endohedral complexes; atoms in molecules.; imidazoles; intermolecular interactions; kinetic stability; reduced
  density gradient; thermodynamic stability