Sharif Digital Repository

In recent years, there has been increasing interest in damaged DNA and RNA nucleobases. These damaged nucleobases can cause DNA mutation, resulting in various diseases such as cancer. Alkylating agents are mutagenic and carcinogenic in a variety of prokaryotic and eukaryotic organisms. The present study employs density functional theory (DFT/B3LYP) with the 6-311++G(d,p) basis set to investigate the effect of chemical damage in O-alkyl pyrimidines such as O4-methylthymine, O2-methylcytosine and O 2-methylthymine. We compared the intrinsic properties, such as proton affinities, gas phase acidities, equilibrium tautomerization and nucleobase pair's hydrogen bonding properties, of these... 

Glutathione tripeptide (γ-glutamyl-cysteinyl-glycine) is a flexible molecule and its conformational energy landscape is strongly influenced by forming intramolecular hydrogen bond, its charge and the environment. This study employs DFT-B3LYP method with the 6-31+G (d,p) basis set to carry out conformational analysis of neutral, zwitterionic, cationic, and anionic forms of glutathione. In analyzing the structural characteristics of these structures, intramolecular hydrogen bonds were identified and characterized in details by topological parameters such as electron density ρ(r) and Laplacian of electron density Δ2 ρ(r) from Bader's atom in molecules theory. Charge transfer energies based on... 

Gas-phase acidities of nucleosides, combined with the knowledge of deprotonation sites, could improve our understanding of chemical reactions to biological systems. In this paper, we mainly focus our attention on the influence of cation coordination on acidities of multiple sites in cytosine nucleosides. The acidities of multiple sites in M +-L (where L represents cytosine nucleosides and M + is an alkali metal ion, including Li +, Na + and K +) complexes have been investigated theoretically, employing B3LY P6-311++G(d,p) basis sets. The geometrical characters, gas-phase acidities, sugar puckering and electronic properties of non-deprotonated and/or deprotonated complexes have been... 

Histidine as a natural amino acid is found to be biologically important and is known to function as a nucleophile or enzyme co-factor, or in proton transfer process. The properties of gaseous aromatic amino acid histidine depend on the structural forms it may take in gas-phase. Ab initio method has been used to characterize the gas-phase conformer/tautomers of histidine. Wide range of possible structures for histidine was surveyed at the MM level, and then the geometries of the unique conformers were refined at the B3LYP/6-311++G (d,p) levels. At this theoretical level, 25 conformers were located for both tautomers of histidine i.e., His [NπH] and His [NτH]. The MM level provides a poor... 

In the present density functional theory study, we have compared intrinsic properties of non-natural nucleobases (acA, acG, acC, and acT nucleobases) such as proton affinities, gas phase acidities, tautomerization, and hydrogen-bonding properties with those in normal Watson-Crick nucleobases (A, G, C, T nucleobases). The hydrogen-bonding interactions in non-natural and Watson-Crick base pairs were studied at B3LYP/6-311++G (d,p) level regarding their geometries, energies, and topological features of the electron density. The quantum theory of atoms-in-molecule (QTAIM) and natural bond orbital (NBO) analyses were employed to elucidate the interaction characteristics in base pairs. The... 

Density functional theory (DFT) calculations were performed at the B3LYP level with a 6-311++G(d,p) basis set to systematically explore the geometrical multiplicity and binding strength for complexes formed by Li+, Na+, and K+ with cytidine and 2′-deoxycytidine. All computational studies indicate that the metal ion affinity (MIA) decreases from Li+ to Na+ and K+ for cytosine nucleosides. For example, for cytidine the affinity for the above metal ions are 79.5, 55.2, and 41.8 and for 2′-deoxycytidine, 82.8, 57.4, and 42.2 kcal/mol, respectively. It is also interesting to mention that linear correlations between calculated MIA values and the atomic numbers (Z) of the above metal ions were... 

Novel bilayer coated mesoporous silica nanoparticle (MCM-41) based on pH sensitive poly(acrylic acid-co-itaconic acid) and human serum albumin (HSA) was designed for controlled delivery of gemcitabine (anticancer drug) to cancer cells. The shell around the mesoporous silica has bilayer structure. Poly(acrylic acid-co-itaconic acid) was used as pH-sensitive inner shell and human serum albumin, HSA, was used as outer shell. The core-shell structure was formed due to electrostatic interaction between ammonium groups of modified MCM-41 and carboxylate groups of copolymer. Also, the albumin layer was wrapped around the copolymer coated nanoparticle by electrostatic interaction between ammonium... 

In this research a novel controlled anticancer drug delivery system with dual pH and thermal responses was designed based on magnetic mesoporous silica nanoparticles that were anchored by β-cyclodextrin and coated by poly(N-isopropylacrylamide) (PNIPAM). Results demonstrated that the behavior of doxorubicin (anticancer drug) release depended on pH and temperature conditions. At endosomal pH (pH 5.5) the amount of drug release enhanced because the cap was removed from the pores. Furthermore, PNIPAM shell collapsed above the lower critical solution temperature and the releasing of drug increased. Thus, this nanocarrier would have the potential to be applied in the tumor therapy. © 2017 Taylor... 

Understanding the nature of interaction between metal nanoparticles and biomolecules such as amino acids is important in the development and design of biosensors. In this paper, binding of M3 clusters (M = Au, Ag and Cu) with neutral and anionic forms of histidine amino acid was studied using density functional theory (DFT-B3LYP). It was found that the interaction of histidine with M3 clusters is governed by two major bonding factors: (a) the anchoring N-M and O-M bonds and (b) the nonconventional N-H⋯M and O-H⋯M hydrogen bonds. The nature of these chemical bonds has been investigated based on quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses. In the next... 

Understanding the nature of the interaction between metal nanoparticles and biomolecules has been important in the development and design of sensors. In this paper, structural, electronic, and bonding properties of the neutral and anionic forms of glutathione tripeptide (GSH) complexes with a Au 3 cluster were studied using the DFT-B3LYP with 6-31+G**-LANL2DZ mixed basis set. Binding of glutathione with the gold cluster is governed by two different kinds of interactions: Auâ€"X (X = N, O, and S) anchoring bond and Au··•·•H-X nonconventional hydrogen bonding. The influence of the intramolecular hydrogen bonding of glutathione on the interaction of this peptide with the gold cluster has been... 

Etheno-damaged DNA adducts such as 3,N4- ethenocytosine, N 2,3-ethenoguanine, and 1,N2-ethenoguanine are associated with carcinogenesis and cell death. These inevitable damages are counteracted by glycosylase enzymes, which cleave damaged nucleobases from DNA. Escherichia coli alkyl purine DNA glycosylase is the enzyme responsible for excising damaged etheno adducts from DNA in humans. In an effort to understand the intrinsic properties of these molecules, we examined gasphase acidity values and proton affinities (PA) of multiple sites of these molecules as well as equilibrium tautomerization and base pairing properties by quantum mechanical calculations. We also used calculations to compare... 

Interactions of α-D-glucose with gold, silver, and copper metal clusters are studied theoretically at the density functional theory (CAM-B3LYP) and MP2 levels of theory, using trimer clusters as simple catalytic models for metal particles as well as investigating the effect of cluster charge by studying the interactions of cationic and anionic gold clusters with glucose. The bonding between α-D-glucose and metal clusters occurs by two major bonding factors; the anchoring of M atoms (M = Cu, Ag, and Au) to the O atoms, and the unconventional M.H-O hydrogen bond. Depending on the charge of metal clusters, each of these bonds contributes significantly to the complexation. Binding energy... 

In the present research, two types of drug carriers based on mesoporous silica-coated magnetic graphene oxide, Fe3O4@GO@mSiO2, were synthesised and the pH-responsive behaviour for doxorubicin release was investigated. One type of the carrier was dendrimer-like multi ethylene amine grafted on Fe3O4@GO@mSiO2 and the other was dendrimer-like supramolecular polypseudorotaxane. Herein, α-cyclodextrin was used in the structure of supramolecular nanoparticles as a gatekeeper to inhibit the drug from escaping at neutral pH (the pH of healthy tissue). The drug release profile showed that the supramolecular nanocarrier was more sensitive to the pH changes. The content of drug release was about 100% at... 

Chitosan based polyseudorotaxane was designed as a pH-responsive supramolecular polymeric shell around the mesoporous silica-coated magnetic graphene oxide (Fe3O4@GO@mSiO2). It was used for doxorubicin delivery at cancerous tissue in a controlled manner. The core-shell nanocarrier was formed due to electrostatic interaction between chitosan and carboxylated surface of Fe3O4@GO@mSiO2. The maximum release occurred at pH 5.5 (pH of endosomes) because the shell collapsed at this pH. The drug nanocarrier has potential application in tumor therapy due to good pH-sensitive behavior, improved solubility and high colloidal stability in... 

In the present work a pH responsive drug nanocarrier based on magnetic mesoporous silica nanoparticles (MMSN) and polyethylene glycol-co-polyvinyl pyridine (PEG-co-PVP) was prepared. The core-shell nanocarrier was formed due to electrostatic interaction between protonated polyvinyl pyridine and surface modified MMSN with carboxylate groups. This carrier was used for pH-controllable doxorubicin release. The maximum release was occurred at pH 5.5 (pH of endosomes). This carrier was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, UV-Vis spectrophotometer, scanning electron microscope, and high-resolution transmission electron microscope techniques. Also the... 

In this research, we report a magnetic pH-sensitive polymeric micelle designed for hydrophobic drug carrier in cancer treatment. This carrier was prepared by self-assembly of biodegradable triblock copolymer PEG-PCL-PEG coated on oleate-modified magnetic nanoparticles. The amphiphilic triblock copolymer was synthesized via reaction between the aldehyde group from the hydrophilic component with the amine group of the hydrophobic component. The resulting Schiff base linkage was sensitive to pH. The structure of nanocarrier was characterized by Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance spectroscopy (1H-NMR). Morphology and size of the magnetic... 

Magnetic micelle nanoparticles with thermoresponsive behavior were designed for thermo-triggered paclitaxel delivery. For this purpose, thermoresponsive triblock copolymer poly(N-isopropyl acrylamide)-b-polycaprolactone-b-poly(N-isopropyl acrylamide) was prepared. The magnetic micelle was formed by self-assembly of triblock copolymer on the magnetite which was coated by oleic acid. The size of the magnetic micelle was between 30–40 nm reported by transmission electron microscopy. Also, dynamic light scattering indicated the hydrodynamic diameter was thermal dependent. Moreover, the drug release profile showed thermo-triggered release of paclitaxel. Thus, the smart nanocarrier has potential... 

Magnetic micelle nanoparticles with thermoresponsive behavior were designed for thermo-triggered paclitaxel delivery. For this purpose, thermoresponsive triblock copolymer poly(N-isopropyl acrylamide)-b-polycaprolactone-b-poly(N-isopropyl acrylamide) was prepared. The magnetic micelle was formed by self-assembly of triblock copolymer on the magnetite which was coated by oleic acid. The size of the magnetic micelle was between 30–40 nm reported by transmission electron microscopy. Also, dynamic light scattering indicated the hydrodynamic diameter was thermal dependent. Moreover, the drug release profile showed thermo-triggered release of paclitaxel. Thus, the smart nanocarrier has potential... 

The functionality of multi-stimuli-responsive hydrogels in physiological states is the reason for the increased attention of hydrogels nowadays. Multi-stimuli-responsive hydrogels exhibit tunable changes in swelling or mechanical properties in response to predetermined combinations of stimuli such as pH, temperature, ionic strength, electric field, magnetic field, light, chemical triggers, enzyme concentration, redox species, reactive oxygen species (ROS), and glucose levels. This review summarizes the recent advances in multi-stimuli-responsive hydrogels used in medical approaches. The first part of the review highlights the medical applications of polymer-based and supramolecular hydrogels... 

In the present study, we designed a pH-responsive drug nanocarrier based on polyamidoamine-modified Fe3O4 nanoparticles coated by PEGylated starch-co-poly(acrylic acid). This carrier was used for the controlled release of doxorubicin as an anticancer drug model. The purpose of using the polyethylene glycol moiety is to generate a biostable nanocarrier in blood stream as it has been reported widely in the pharmaceutical literature. The use of a poly(acrylic acid) segment also provided pH-sensitivity to the polymer. Besides, the magnetic nanoparticles facilitate the cancer cell targeting with an external magnetic field located near the tumor site. This carrier was...