Sharif Digital Repository

Acidity values of some compound (e.g., alkanes, alcohols, carboxylic acids and amines) with or without boron substitute have been studied theoretically to evaluate the influence of boron on acidity of organic functional groups. We have derived the unoccupied reactive orbital that show the maximum localization on the boron pπ atomic orbital overlapping with the lone-pair orbital of an electron donor. Localization of unoccupied reactive orbital on the boron pπ atomic and the polarizability of the boron center are two factors which affect acidity values of functional groups. Conformational searching was performed using MM (Molecular Mechanics). The most important conformations were optimized at... 

It is believed that intramolecular hydrogen bonding and also conjugation can affect the acidity power of organic molecules. But simultaneous effects of intramolecular hydrogen bonding and conjugation have not investigated systematically yet. In this project, we choose Ascorbic acid as a basic structure. Then we have changed its structure conveniently, and have explored the roles of hydrogen bonding and conjugation on the acidity of this molecule by using B3LYP functional with the 6-311++G(d,p) basis set. After that we similarly investigate these effects on the acidity of three different systems, including enols, enamines and alcohols. In this project we probe the effect of different hydrogen... 

This project aims to design a novel structure that can inhibit the activitvation of the c-Met enzyme using amino acids and sugars building blocks. The c-Met enzyme is a receptor tyrosine kinase that plays a significant role in several biological activities such as cell proliferation, survival, and invasion. Abnormal activity of the enzyme is linked to the progression of various types of cancer, including breast, lung, liver, and stomach cancer. The proposed sugar amino acid conjugate structures is expected to increase stability amino acids and dipeptides in the physiological environment, improve membrane permeability via active transport mechanism, and reduce toxicity and side effects by... 

Vimseltinib, a small molecule inhibitor, represents a promising avenue for combating cancers linked to macrophage-associated processes through its targeted action on the CSF1R tyrosine kinase receptor. CSF1R, a pivotal member of the tyrosine kinase receptor family, plays a crucial role in macrophage differentiation and function. This protein's significance is underscored in conditions such as tenosynovial giant cell tumors (TGCTs) and the presence of tumor-associated macrophages, wherein overproduction of CSF1 by neoplastic cells recruits CSF1R-dependent immune cells, fostering tumor expansion. The intricate interplay extends to tumor-associated macrophages, particularly the M2 subtype,... 

N, N′, N″-triethylenethiophosphoramide (Thiotepa) and its oxo analogue (Tepa) as the major metabolite are trifunctional alkylating agents with a broad spectrum of antitumor activity. In vivo and vitro studies show alkylation of DNA by Thiotepa and Tepa can follow two pathways, but it remains unclear which pathway represents the precise mechanism of action. In pathway 1, these agents are capable of forming cross-links with DNA molecules which can be carried out via two different mechanisms. In the first mechanism, the ring opening reaction is initiated by protonating the aziridine, which then becomes the primary target of nucleophilic attack by the N7-Guanine of DNA. The second one is the... 

Many of the significant reactions in chemistry and biology are related to bimolecular nucleophilic substitution (SN2) reactions which have been studied first by Hughes and Ingold in the 1930s. Afterward, many organic chemists have continued this work. Up to now, numerous experimental kinetic and theoretical researches have studied the mechanism of these reactions. Since most SN2 reactions occur in solution, a large number of these studies have been devoted to the solvent effects. One of these effects that has been examined extremely is H-bonding via protic solvents that lowers the energy of an anionic nucleophile relative to the transition state, in which the charge is more diffuse, and... 

Since we are exposed to many air pollutants such as different gases daily, this project has attempted to investigate how these gases affect nucleobases, which are the main constituent of the DNA chain. The gases used in this study are sulfur dioxide (SO2), carbon monoxide (CO) and nitric oxide (NO). Each of these gases was studied separately along with the most stable nucleobase in the neutral, anionic and cationic states. The AT and GC base pairs were also exposed to each of these gases and changes (for exampl, the acidity, proton affinity) created in the AT and GC base pairs were examined.The most important properties studied during this project include gas-nucleobase interactions, proton... 

Nowadays, there is no doubt about the importance of investigation of physicochemical properties of nucleosides in order to determine the structure of these biopolymers. Nucleotides have a variety of roles in cellular metabolism. They are the constituents of nucleic acids: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), the molecular repositories of genetic information. The metal ions play a significant role in several biological processes. Synthesis, replication, and cleavage of DNA and RNA as well as their structure integrity are affected by the presence of these ionized metals in the cell nucleus. To understand the role of cations in the biophysics of DNA, it is necessary first to... 

Present work focuses on the influence of Heteroatom(s) on the bacisity of specific group of amines through the intramolecular hydrogen bonding. This group includes Aza-Crown Ethers specifically. We used Spartan and Gaussian packages to gain optimized structures for all compounds in order to explore the influence of the intramolecular hydrogen bonding on the bacisity of amines. All the gas phase optimizations and energy calculations were performed at the DFT/B3LYP/6-311++G(d,p) level of theory. The Hf/6-31+G(d,p) level was used for all single point calculations in the solution phase. As commonly used solvents in organic and biological reactions, the solution phase calculations were carried... 

This project aims to design a drug to fight leukemia and some autoimmune diseases having few side effects. These drugs are composed of natural sugar and amino acid structures. Among the various treatments available, drug structures as inhibitors of enzymes involved in cancer-related cellular processes is an important treatment. Methotrexate is one of the most widely used anticancer drugs in the last half-century and treats leukemia and many autoimmune diseases such as psoriasis. It is a derivative of folic acid (vitamin B9) and one of the drugs with specific properties. It is an anti-folate whose anti-metabolic effects can help kill cancer cells. One of the problems with using this drug to... 

The aim of this study is to devise innovative compounds that impede the function of CK2α enzyme by incorporating amino acids and sugars into their molecular structure. CK2α, a catalytic subunit of CK2 enzyme, operates autonomously and is the only continuously active kinase that does not require an upstream regulator. Emerging evidence highlights CK2α's crucial role in various cancers and infectious diseases, including Covid-19, indicating that suppressing its function could provide a promising approach to improve patient outcomes. To accomplish this objective, the drug design process must take into account both pharmacokinetic and pharmacodynamic properties. Pharmacokinetics, encompassing... 

Hydrogen bond is a type of molecular bonds which occurs between hydrogen and a highly electronegative atom( usually F, N and O) and results to special properties. Polyols and multihydroxyl compounds are among substances which have special properties such as acidity due to the existence of hydrogen bond in their molecular structure. Acidity in these compounds is a result of having stable anions due to intramolecular hydrogen bands. The existence of an electronegative group in addition to hydroxyl groups leads to increase the acidity in these substances. In this project acidities of some polyols and multihydroxyl compounds were calculated in both gas phase and solution phase( DMSO,... 

In this study, using the B3LYP/6-3111++g(d,p) computational level, we have explored the possibility of formation of some organic and bioorganic cation-cation clusters (CCC) in the absence of any anionic stabilizing species. Furthermore, we have shown the existence of a barrier energy for exothermic dissociation of these clusters. Herein, we have selected some biomolecules such as the chloroquine (CQ) antimalarial drug . The selected molecules possess the basic sites and can function as both hydrogen bond donors and acceptors. Also, a facile and direct synthetic route toward the rhodanine derivatives and thiazolidine-2,4-diones via a three-component coupling of carbon disulfide, primary... 

Quantum calculation based on the density functional theory (DFT) level and 6-311++G (d,p) basis set was employed to study the relation between the structure and radical scavenging activity of a series of hydroxybenzohydroxamic acid derivatives, namely: [HU]; hyroxyurea, [TX]; 3,4,5-trihydroxybenzamidoxime, [DX]; 3,4-dihydroxybenzohydroxamic acid, [4-HBA]; 4-hydroxybenzohydroxamic acid, [2,3-DHBA]; 2,3-Dihydroxybenzohydroxamic acid, [3,5-DHBA]; 3,5-Dihydroxybenzohydroxamic acid and [2-HBA]; 2-hydroxybenzohydroxamic acid in the gas phase, water and benzene environments. The hydrogen bond property of the studied structures and their radicals as well as radical cations was investigated using... 

This thesis is divided into two parts: In part I, which is theoretical part, we were looking for a computational method which is extensively comparable with experimental results to determine pKa of wide variety of organic compounds. The pKa is an important property in many sciences such as chemistry, biology, and material science, since inclination of a compound to donate or accept a proton is fundamental to understanding many chemical and biochemical processes. Experimentally determined pKa values are not always available from literature sources and often estimated values are employed in their place. It is useful, therefore, to have reliable and accurate means of calculating relative and/or... 

Hydrogen bonding is an important weak interaction encountered in gas, liquid, as well as solid phase. The hydrogen bond plays a very vital role in many life processes and is one of the most frequently used terms in chemistry and biology. Amides have several applications as drugs, antibacterials and antifungals. Different substituents can affect the acidity of amides. Investigation have shown that hydroxyl function group can increase the acidity of many organic molecules through interamolecular hydrogen bonding. The goal of this project is to investigate the acidity of cyclic amides and barbiturates by adding hydroxyl group in the gas and solution phase. All the gas phase optimizations and... 

Hydrogen bonding is an important weak interaction encountered in gas and liquid, as well as solid phase. The hydrogen bond plays a very vital role in many life processes and is one of the most frequently used terms in chemistry and biology. Beta diketones have several applications in organic, inorganic and analytical chemistry. Different substituents can affect the acidity of beta diketones. Investigation have shown that hydroxyl function group can increase the acidity of many organic molecules through interamolecular hydrogen bonding. The goal of this project is to investigate the acidity of hydroxyl containing beta diketones in the gas and solution phase. All the gas phase optimizations... 

1- Mesoporous silica materials have been found to possess pore sizes ranging from 2 -10 nm alongside 2D-hexagonal and 3D-cubic structural features. The specific properties of nanoparticles of the mesoporous silica family, such as the collected size, porosity, morphology, and high chemical stability, make them among the best drug delivery systems and catalysts. Designing the catalysts with advanced structures that effectively locate the transition metals and create active centres onto the surfaces of mesoporous silica materials has attracted extraordinary attention. According to many studies, mesoporous silica materials without organic functional groups cannot be used as catalysts in chemical... 

One of the goals of the current research is to investigate natural structures to inhibit Ras proteins that belong to the family of guanosine triphosphatase proteins. For example, one of the common mutations is Kras mutations, which are seen exclusively in pancreatic ductal adenocarcinoma. Changes in Kras protein expression are observed in 30 percent of lung cancer cases. Kras mutations occur in 35-45 percent of colon cancers, leading to drug resistance. Our work method in this research is that we collect a dataset of natural compounds for the target protein. Then, the binding energies of these structures with the receptor protein are calculated through Autodoc Vina. After that, using deep... 

Telework is an adaptable method for working which covers an extensive variety of work exercises in circulated associations comprised of people with robots and independent frameworks. From the levels of Nano and micro frameworks and gadgets the distance to the level of worldwide undertaking systems, beneficial work is reshaped by E-Work or Telework or Telecommute. The current work stresses on the part of learning administration as an empowering influence of E-Working standard. The four primary circles of information in e-Work related are: ‘‘e-Work”, ‘‘Integration , Coordination and Collaboration”, ‘‘Distributed Decision Support” and ‘‘Active Middleware”. Cloud computing can be distinguished...