A theoretical investigation on the synergetic effect of hydrogen-bonding interactions and thermodynamic property in the 1: 2 (azacyclopentane-2-one: N-methylolacetamide) ternary complex.

CONTEXT: Using chemical penetration enhancers to improve the penetration effect is one kind of important strategies in transdermal drug delivery system. Azone is a widely used transdermal absorption enhancer for transdermal drug delivery. To shed light on the permeation-promoting mechanism of azone, we selected ternary systems formed by azacyclopentane-2-one and N-methylolacetamide (1: 2) and explored the synergetic effect of hydrogen-bonding interactions among them and their thermodynamic properties. The findings indicate that the synergetic effects can enhance the ability of azone to change the original conformation of ceramides and even break the original hydrogen bonds, which is more beneficial for azone to destroy the 3D network structure of ceramides. When azone interacts with ceramide, the order of action tends to interact with one molecule of ceramide first and then with another molecule of ceramide. METHODS: The synergetic effects of hydrogen-bonding interactions in ternary systems were computed at the B3LYP/6-311 + + G** and MP2(full)/6-311 + + G** levels. Thermodynamic parameters for two ternary-complex routes were worked out at the B3LYP/aug-cc-pVDZ level. The shift of the electron density occurring simultaneously with trimer formation was analyzed at the MP2(full)/6-311 + + G** level. The above calculations were carried out using the Gaussian 03 program packages. Atoms in molecules (AIM) method and the AIMPAC program showed the topological charge density at the MP2(full)/6-311 + + G** level. The synergetic effects of hydrogen-bonding interactions and thermodynamic property in the 1: 2 (azacyclopentane-2-one: N-methylolacetamide) ternary systems were investigated using the B3LYP and MP2(full) methods.

Theoretical investigations into the intermolecular hydrogen-bonding interactions of N-(hydroxymethyl)acetamide dimers.

The structures of the N-(hydroxymethyl)acetamide (model molecule of ceramide) dimers have been fully optimized at B3LYP/6-311++G** level. The intermolecular hydrogen bonding interaction energies have been calculated using the B3LYP/6-311++G**, B3LYP/6-311++G(2df,2p), MP2(full)/6-311++G** and MP2(full)/6-311++G(2df,2p) methods, respectively. The results show that the O-H···O, N-H···O, O-H···N, and C-H···O hydrogen bonding interactions could exist in N-(hydroxymethyl)acetamide dimers, and the O-H···O, N-H···O, and O-H···N hydrogen bonding interactions could be stronger than C-H···O. The three-dimensional network structure formed by ceramide molecules through intermolecular hydrogen bonding interactions may be the main reason why the stratum corneum of skin could prevent foreign substances from entering our body, as is in accordance with the experimental results. The stability of hydrogen-bonding interactions follow the order of (a) > (b) ≈ (c) > (d) > (e) ≈ (f) > (g) > (h). The analyses of the energy decomposition, frequency, atoms in molecules (AIM), natural bond orbital (NBO), and electron density shift are used to further reveal the nature of the complex formation. In the range of 263.0-328.0 K, the complex is formed via an exothermic reaction, and the solvent with lower temperature and dielectric constant is favorable to this process. Graphical abstract The structures and the O-H···O=C, N-H···O=C and C-H···O=C H-bonding interactions in the N-(hydroxymethyl)acetamide (model molecule of ceramide) dimers were investigated using the B3LYP and MP2(full) methods.

A theoretical investigation into the cooperativity effect between the H∙∙∙O and H∙∙∙F⁻ interactions and electrostatic potential upon 1:2 (F⁻:N-(Hydroxymethyl)acetamide) ternary-system formation.

The cooperativity effects between the O/N-H∙∙∙F(-) anionic hydrogen-bonding and O/N-H∙∙∙O hydrogen-bonding interactions and electrostatic potentials in the 1:2 (F(-):N-(Hydroxymethyl)acetamide (signed as "ha")) ternary systems are investigated at the B3LYP/6-311++G** and MP2/6-311++G** levels. A comparison of the cooperativity effect in the "F(-)∙∙∙ha∙∙∙ha" and "FH∙∙∙ha(-)∙∙∙ha" systems is also carried out. The result shows that the increase of the H∙∙∙O interaction energy in the O-H∙∙∙O-H, N-H∙∙∙O-H or N-H∙∙∙O = C link is more notable than that in the O-H∙∙∙O = C contact upon ternary-system formation. The cooperativity effect is found in the complex formed by the O/N-H∙∙∙F(-) and O/N-H∙∙∙O interactions, while the anti-cooperativity effect is present in the system with only the O/N-H∙∙∙F(-) H-bond or the "FH∙∙∙ha(-)∙∙∙ha" complex by the N(-)∙∙∙H-F contact. Atoms in molecules (AIM) analysis and shift of electron density confirm the existence of cooperativity. The most negative surface electrostatic potential (V(S,min)) correlates well with the interaction energy E' int.(ha∙∙∙F-) and synergetic energy E(syn.), respectively. The relationship between the change of V(S,min) (i.e., ΔV(S,min)) and E(syn.) is also found.

A novel one-step synthesis of Gd3+-incorporated mesoporous SiO2 nanoparticles for use as an efficient MRI contrast agent.

Molecular imaging has generated a demand for more sensitive contrast agents for magnetic resonance (MR) imaging. We synthesized, by a novel one-step method, Gd(3+) incorporated mesoporous SiO(2) nanoparticles, Gd(2)O(3)@SiO(2), for use as an efficient contrast agent. The prepared nanoparticles were also coated with poly(lactic-co-glycolic acid) (PLGA). The size, morphology, composition and Brunauer-Emmett-Teller specific surface area of the nanoparticles were evaluated. The Gd(2)O(3)@SiO(2) nanoparticles possess intragranular network morphology with a uniform size distribution and an average size of approximately 20-40 nm. The PLGA-coated nanoparticles were spherical or near-spherical in shape with a diameter of approximately 120 nm, a smooth surface, and neither aggregation nor adhesion tendencies. No free Gd ions were detected to dissociate from Gd(2)O(3)@SiO(2) even up to the limit (<0.03 mg/l) of the ICP equipment (IRIS Advantage). Our theoretical computation based on density functional theory (using DMol3, Materials Studio) revealed that the Gd(2)O(3) molecules are fully absorbed on the interface of mesoporous SiO(2) with a stable state of lower energy. Both Gd(2)O(3)@SiO(2) and PLGA-coated Gd(2)O(3)@SiO(2) samples have a larger T(1) relaxivitiy than commercial gadolinium diethylene triaminepentaacetate (Gd-DTPA). In vitro and in vivo MR images using the Gd(2)O(3)@SiO(2) nanoparticles were observed with a 1.5 T clinical MR scanner and compared with the images using Gd-DTPA. The Gd(2)O(3)@SiO(2) nanoparticles display a better magnetic property than commercial Gd-DTPA. In vivo MR imaging demonstrated that the nanoparticles were mainly distributed in the liver. Strong enhancement was also detected in nasopharyngeal carcinoma CNE-2 xenografted tumors. The Gd(2)O(3)@SiO(2) nanoparticles are not only potential candidates for highly efficient contrast agents for MR imaging, but also might be developed into potent targeted probes for in vivo molecular imaging of cancer.