Prodrugs Designed by DFT and Molecular Mechanics Methods | Chapter 05 | Modern Advances in Pharmaceutical Research Vol. 2

The accumulation of knowledge on intramolecular processes, enzymes and transporters along with the vast progress in molecular revolution have accelerated the search for prodrugs having the capability to replace their corresponding current marketed drugs and to provide therapeutics with better pharmacological profiles. Utilizing the different available computational methods has led to the design and synthesis of a variety of prodrugs to replace their corresponding parent drugs.

It has been proven that prodrugs can significantly improve the life quality of patients.

The directed enzyme prodrug therapy (DEPT) approach to employ the design of artificial enzymes to activate prodrugs at specific sites along with use of intramolecular processes to design prodrugs are the most attractive strategies to obtain more efficient therapeutics.

Author(s) Details

Professor Rafik Karaman
Department  of  Bioorganic  Chemistry,  Faculty  of  Pharmacy,  Al-Quds  University,  P.O.Box  20002,  Jerusalem,  Palestine and Department of Sciences, University of Basilicata, Via dell’ateneo Lucano 10, 85100, Potenza, Italy.

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Reflections on the Use of Density Functional Theory in the Understanding of the Effects of Moderate Amounts of Sulfur Substitutional Impurities on ZnO | Chapter 06 | New Advances in Materials Science and Engineering Vol. 1

A theoretical study on the effects of a moderate amount of sulfur when used as substituent impurity in place of oxygen in zinc oxide at its crystal form using Density Functional Theory (DFT). S-substituent amounts in percent go from 0.1% up to 1.0% and we analyze modifications in the crystal properties such as lattice characteristics, total energy, and gap energy. Lattice parameter c increased slightly as S-substituent percent increased, lattice parameter a had an opposite behavior because it decreased as the S-substituent increased and c/a rate had ups and downs but with very slight variation between consecutive values. Total energy calculations showed an increasing trend at all times and binding energy showed a decreasing trend at all times as the substituent percent increase but the variation between consecutive points was small. Gap energy had a decreasing trend with a maximum variation of 6.57% at 1.0% S substituent from pristine ZnO. In order to correct the DFT underestimation of gap energy we applied a correction factor and found a decreasing trend as the substituent percent increase and observed the highest difference from undoped ZnO was 1.42% at 1.0% S-substituent. We study the effects on the ZnO structure occurring when moderate S-substituent amounts from 0.1% to 1.0% are used and provide new knowledge to predict if the geometric and electronic structure changes may be suitable for new applications of ZnO in optoelectronics.

Author(s) Details

Manuel Alberto Flores-Hidalgo
Facultad de Ciencias Qu´ımicas, Universidad Ju´arez del Estado de Durango, Durango, Durango 34120, Mexico.

Diana Barraza-Jim´enez
Facultad de Ciencias Qu´ımicas, Universidad Ju´arez del Estado de Durango, Durango, Durango 34120, Mexico.

Daniel Glossman-Mitnik
Laboratorio Virtual NANOCOSMOS, Departamento de Medio Ambiente y Energ´ıa, Centro de Investi- gaci´on en Materiales Avanzados, Chihuahua, Chih 31136, Mexico.

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A Comparative Study of Two Different Media Effect on the Electropolymerization of 2-(9-ethylcarbazol-3- yliminomethyl)phenol by Cyclic Voltammetry, Impedance Spectroscopy, XPS, UV-visible Measurements and DFT Calculation | Chapter 9 | Theory and Applications of Chemistry Vol. 2

A carbazole-based monomer, 2-(9-ethylcarbazol-3-yliminomethyl)phenol (SIC), was first synthesized and characterized. It was afterward polymerized by potentiostatic methods. Oxidative polymerization of SIC was carried out in two media. The first one (i.e. Bu4NBF4 (0.1M)/MeCN) gives the poly(2-(9- ethylcarbazol-3-yliminomethyl)phenol). However, the second one (LiClO4/MeCN + 35mM HClO4), leads to another polymer, the poly(2-(9-ethylcarbazol-3-yliminomethyl)cyclohexa-2,5-diene-1,4- dione).These two novel polymers will be abbreviated here after as PSIC and PDIC, respectively. If the formation of PSIC was expected, the formation of PDIC in acidic medium isn’t. It was explained by a hydroxyl function oxidation of SIC. The obtained polymers were then characterized by cyclic voltammetry, electrochemical impedance spectroscopy, XPS, IR and UV-Vis spectroscopies. Furthermore, the corresponding electrochemical and optical bandgap values were calculated in order to get an idea about the conductive properties. The related results show that PDIC and PSIC are good conductive polymers. The electrochemical polymerisation of SIC is performed in both protic and organic medium. During the anodic oxidation in protic medium containing LiClO4/MeCN + (35mM) HClO4, SIC undergoes hydrolysis around 1V, which modifies its structure before its polymerization. This reaction is very fast, and leads to the formation of two isomers, para-quinone and ortho-quinone (DIC) which oxidizes at the same potential and form PDIC. In the organic medium, the SIC retains its initial structure, and leads after oxidation to the corresponding polymer PSIC. The electrochemical behaviour of PSIC and PDIC supports the conductive character of both polymers and the difference between their structures. In an acidic medium, the imine bond undergoes a protonation which increases commonly the planarity of the polymeric material and subsequently, improves its electrical properties. The charge transfer resistance recorded for the PDIC film was much lower than the one recorded for the PSIC film. The electrochemical and the optical bandgaps of PDIC are lower than those of PSIC. The difference in structures of both polymers could explain these results. Compared to SIC, para-quinone and ortho-quinone compounds are formally electrons donor-acceptor (D-A) type moieties. In a D-A system, a charge transfer from the donor to the acceptor increases conjugation length through resonance which causes the decrease of its bandgap. Therefore, these findings indicate that PDIC is more conductive than PSIC.

Author(s) Details

Mounia Guergouri
Laboratoire de Chimie des Matériaux Constantine, Université des Frères Mentouri, Constantine 25000, Algeria.

Rafik Bensegueni
Université Mohamed Cherif Messaadia, 41000 Souk Ahras, Algeria.

Ammar Khelifa Baghdouche
Laboratoire de Chimie des Matériaux Constantine, Université des Frères Mentouri, Constantine 25000, Algeria.

Leila Bencharif
Laboratoire de Chimie des Matériaux Constantine, Université des Frères Mentouri, Constantine 25000, Algeria.

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Semiconducting Oligomers of 1,4-dimethoxybenzene, Thiophene and Thiazole: A Theoretical Study | Chapter 1 | Theory and Applications of Chemistry Vol. 2

Organic semiconducting oligomers containing three to nine heterocyclic units and based on 1,4-dimethoxybenzene, thiophene and thiazole have been studied by DFT and TDDFT at the B3LYP/6-31G(d,p)  level.  The energy  of  each  molecule,  those  of  the frontier orbitals  HOMO and  LUMO,the width  of  the  band  gaps  and  the  optical  properties  have  been  calculated. The inter-ring distances, dihedral angles and torsional angles have been elucidated. These molecules are planar π-conjugated systems. The  band  gaps  of  the  longer  oligomers  studied  range  from  2.53  to  2.72  eV  and  their excitation  energies  calculated  by  TDDFT  vary  from  2.22  to  2.36  eV. Wavelengths of absorption bands of 524 to 556 nm are also obtained by TDDFT. The results of this theoretical study show that these organic molecules have interesting properties and can potentially be used as components in solar cells. In this work, a theoretical investigation on the geometries and optoelectronic properties of oligomers based on 1,4-dimethoxybenzene, thiophene and thiazole has been done. Molecules that contain up to nine rings have been studied. For all these oligomers, the elongation of the molecular chain led to a gradual decrease of the energy gap between the frontier orbitals. This energy splitting varied from 2.5 to 3.7 eV. This indicates that these compounds may exhibit semi-conducting properties. The increase  in  the  molecular chain length  also  induced  a  decrease  in  the  excitation energy determined by TDDFT. These oligomers present many intra and inter-unit interactions which contribute to their rigidity and to a better delocalization of the π-electrons.

Author(s) Details

Diendéré Françoise
Laboratoire de Chimie Moléculaire et des Matériaux, Université de Ouagadougou, UFR/SEA 03 BP 7021, Burkina Faso.

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Prodrugs-Current and Future Drug Development Strategy | Chapter 7 | Modern Advances in Pharmaceutical Research Vol. 1

The  focus  of  traditional  prodrug  approach  was  on  altering  various  physiochemical  parameters, whereas the current modern computational approach considers designing prodrugs through attaching appropriate  linkers  with  drugs  having  poor  bioavailability  which  upon  exposure  to  physiological environments release the parent active drugs in a programmable (controlled) manner resulting in an improvement of their bioavailability. With the possibility of designing prodrugs with different linkers, the release rate of the parent active drugs can be controlled. The future of  prodrug  technology  is  exciting  and  yet  challenging. Advances must be made in understanding the chemistry of many organic reactions that can be effectively utilized to enable the development of more types of prodrugs. The understanding of organic reaction mechanisms of certain processes, particularly intramolecular reactions, will be the next major milestone in this field. It is envisioned that the future of prodrug technology holds the  ability  to  create  safe and  efficacious delivery of a wide range of active small molecules and biotherapeutics. This goal can be achieved using computational chemistry methods such as ab initio, semi-empirical and density functional theory (DFT), and molecular mechanics (MM) to calculate physicochemical and molecular  properties of current marketed drugs suffer low bioavailability or/and unpleasant taste or odor.

Author(s) Details

Professor Rafik Karaman
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Quds University, P.O. Box 20002, Jerusalem, Palestine and Department of Science, University of Basilicata, Potenza, Italy.

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