Shariatinia Zahra, Shahidi Samira
Department of Chemistry, Amirkabir University of Technology, P.O. Box: 15875-4413, Tehran, Iran.
Department of Chemistry, Amirkabir University of Technology, P.O. Box: 15875-4413, Tehran, Iran.
J Mol Graph Model. 2014 Jul;52:71-81. doi: 10.1016/j.jmgm.2014.06.001. Epub 2014 Jun 16.
The physical sorption of a series of cyclophosphamide drug derivatives with formula [NH(CH2)3O]P(O0(N[CH2)(x)X]2) where x=2, X=F (2), Cl (3), Br (4); x=3, X=F (5), Cl (6), Br (7) and x=4, X=F (8), Cl (9), Br (10) on the surface of fullerene C60 was studied using density functional theory (DFT) at B3LYP and B3PW91 levels. The most negative binding energies obtained using the B3LYP approach and corrected for geometrical BSSE and dispersion energies (gCP-D3-ΔE(binding)) were measured for compounds 8 (among isolated drugs) and 13 (among complexes). The dipole moments of isolated drugs were obtained close to those of their complexes with C60 (∼4.0-5.5 Debye) indicating their hydrophililic nature that is an appropriate property appealing for drug delivery in biological media. The adsorption of all drugs on the surface of fullerene was endergonic with all of the ΔG(adsorption)>0. The ΔH(adsorption) values at B3PW91 level were only negative for complexes 14-16 indicating their exothermic adsorption nature. The HOMO-LUMO band gaps of complexes 11-19 were about 2.7 eV and are comparable with the gap in C60 but are much smaller than the gaps in isolated drugs 2-10 (6.5-8.0 eV) reflecting the increase in electrical conductivities upon complexation. The QTAIM data supported the covalent character of the C-O, C-N and N-H bonds, the intermediate character of PO, P-O and P-N bonds while the electrostatic nature of PO…C(fullerene) interactions. According to the gCP-D3-ΔE(binding) binding energies and ΔH(adsorption) values at B3LYP level, it seems that the complexes 12 and 13 can be the most promising prodrug+carrier delivery systems.
使用密度泛函理论（DFT）在B3LYP和B3PW91水平上研究了一系列通式为[NH(CH2)3O]P(O)(N[CH2)(x)X]2（其中x = 2，X = F (2)、Cl (3)、Br (4)；x = 3，X = F (5)、Cl (6)、Br (7)；x = 4，X = F (8)、Cl (9)、Br (10)）的环磷酰胺药物衍生物在富勒烯C60表面的物理吸附。使用B3LYP方法获得并经几何基组重叠误差（BSSE）和色散能校正（gCP-D3-ΔE(binding)）的最负结合能，在化合物8（在分离的药物中）和13（在配合物中）中测得。分离药物的偶极矩与其与C60的配合物的偶极矩相近（约4.0 - 5.5德拜），表明其亲水性，这是在生物介质中进行药物递送的合适性质。所有药物在富勒烯表面的吸附都是吸热的，所有的ΔG(吸附)>0。在B3PW91水平下，只有配合物14 - 16的ΔH(吸附)值为负，表明其吸附具有放热性质。配合物11 - 19的HOMO - LUMO带隙约为2.7 eV，与C60中的带隙相当，但比分离药物2 - 10中的带隙（6.5 - 8.0 eV）小得多，反映出络合后电导率的增加。QTAIM数据支持C - O、C - N和N - H键的共价性质，PO、P - O和P - N键的中间性质，而PO…C(富勒烯)相互作用的静电性质。根据B3LYP水平下的gCP-D3-ΔE(binding)结合能和ΔH(吸附)值，似乎配合物12和13可能是最有前途的前药+载体递送系统。
