scholarly journals Enzyme Models—From Catalysis to Prodrugs

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3248
Author(s):  
Zeinab Breijyeh ◽  
Rafik Karaman
Keyword(s):  
Tranexamic Acid ◽  
Physicochemical Properties ◽  
Experimental Research ◽  
Enzyme Catalysis ◽  
Antibacterial Agents ◽  
Minimum Energy ◽  
Cefuroxime Axetil ◽  
Quantum Mechanical ◽  
Enzymatic Reactions ◽  
Enzyme Models

Enzymes are highly specific biological catalysts that accelerate the rate of chemical reactions within the cell. Our knowledge of how enzymes work remains incomplete. Computational methodologies such as molecular mechanics (MM) and quantum mechanical (QM) methods play an important role in elucidating the detailed mechanisms of enzymatic reactions where experimental research measurements are not possible. Theories invoked by a variety of scientists indicate that enzymes work as structural scaffolds that serve to bring together and orient the reactants so that the reaction can proceed with minimum energy. Enzyme models can be utilized for mimicking enzyme catalysis and the development of novel prodrugs. Prodrugs are used to enhance the pharmacokinetics of drugs; classical prodrug approaches focus on alternating the physicochemical properties, while chemical modern approaches are based on the knowledge gained from the chemistry of enzyme models and correlations between experimental and calculated rate values of intramolecular processes (enzyme models). A large number of prodrugs have been designed and developed to improve the effectiveness and pharmacokinetics of commonly used drugs, such as anti-Parkinson (dopamine), antiviral (acyclovir), antimalarial (atovaquone), anticancer (azanucleosides), antifibrinolytic (tranexamic acid), antihyperlipidemia (statins), vasoconstrictors (phenylephrine), antihypertension (atenolol), antibacterial agents (amoxicillin, cephalexin, and cefuroxime axetil), paracetamol, and guaifenesin. This article describes the works done on enzyme models and the computational methods used to understand enzyme catalysis and to help in the development of efficient prodrugs.

Seemingly Anomalous Angular Distributions in H + D2 Reactive Scattering

Science ◽  
2012 ◽  
Vol 336 (6089) ◽  
pp. 1687-1690 ◽  
Author(s):  
Justin Jankunas ◽  
Richard N. Zare ◽  
Foudhil Bouakline ◽  
Stuart C. Althorpe ◽  
Diego Herráez-Aguilar ◽  
...  
Keyword(s):  
Cross Sections ◽  
Collision Energy ◽  
Minimum Energy ◽  
Angular Distributions ◽  
Quantum Mechanical ◽  
Minimum Energy Path ◽  
Reactive Scattering ◽  
Rotational Excitation ◽  
Reaction Products ◽  
Trajectory Calculations

When a hydrogen (H) atom approaches a deuterium (D2) molecule, the minimum-energy path is for the three nuclei to line up. Consequently, nearly collinear collisions cause HD reaction products to be backscattered with low rotational excitation, whereas more glancing collisions yield sideways-scattered HD products with higher rotational excitation. Here we report that measured cross sections for the H + D2 → HD(v′ = 4, j′) + D reaction at a collision energy of 1.97 electron volts contradict this behavior. The anomalous angular distributions match closely fully quantum mechanical calculations, and for the most part quasiclassical trajectory calculations. As the energy available in product recoil is reduced, a rotational barrier to reaction cuts off contributions from glancing collisions, causing high-j′ HD products to become backward scattered.

How Important Are Quantum Mechanical Nuclear Motions in Enzyme Catalysis?

1996 ◽  
Vol 118 (47) ◽  
pp. 11745-11751 ◽  
Author(s):  
Jenn-Kang Hwang ◽  
Arieh Warshel
Keyword(s):  
Enzyme Catalysis ◽  
Quantum Mechanical

scholarly journals Accelerated Computation of Free Energy Profile at Ab Initio Quantum Mechanical/Molecular Mechanics Accuracy via a Semiempirical Reference-Potential. 4. Adaptive QM/MM

2020 ◽  
Author(s):  
Jia-Ning Wang ◽  
Wei Liu ◽  
Pengfei Li ◽  
Yan Mo ◽  
Wenxin Hu ◽  
...  
Keyword(s):  
Molecular Mechanics ◽  
Computational Cost ◽  
Potential Method ◽  
Quantum Mechanical ◽  
Enzymatic Reactions ◽  
Energy Functions ◽  
Potential Energy Functions ◽  
Reference Potential ◽  
Nucleophilic Addition Reaction ◽  
Solvent Molecules

Although Quantum Mechanical/Molecular Mechanics (QM/MM) methods are now routinely applied to the studies of chemical reactions in condensed phases and enzymatic reactions, they may confront technical difficulties when the reactive region is varying over time. For instance, when the solvent molecules are participating in the reaction, the exchange of water molecules between the QM and MM regions may occur on a time scale that is comparable to that of the reaction. Several adaptive QM/MM schemes have been proposed to cope with this situation. However, these methods either significantly increase the computational cost or introducing unrealistic restraints to the system. In this work, we developed a novel adaptive QM/MM scheme and applied it to a study of the nucleophilic addition reaction. In this approach, the simulation was performed with a small QM region (without solvent molecules), and the thermodynamic properties under other potential energy functions with larger QM regions (with a different number of solvent molecules and/or different level of QM theory) are computed via extrapolation using the reference-potential method. The results show that this reweighting process is numerically stable, at least for the case studied in this work. Furthermore, this method also offers an inexpensive way to examine the convergence of the QM/MM calculation with respect to the size of the QM region.<br>

1.3 Modelling Radicals and Their Reactivities

2021 ◽  
Author(s):  
E. Derat ◽  
B. Braïda
Keyword(s):  
Horseradish Peroxidase ◽  
Quantum Chemical ◽  
Valence Bond ◽  
Radical Reactions ◽  
Experimental Investigations ◽  
Quantum Mechanical ◽  
Enzymatic Reactions ◽  
Mechanical Methods ◽  
Electronic Configurations ◽  
Computational Quantum

AbstractIn this chapter, the application of computational quantum mechanical methods to the understanding of radical reactions is introduced. For radical reactions, access to electronic configurations through quantum chemical calculations allows rationalization of unusual reactivities. Using the valence bond approach, the nature of bonding in three-electron bonds can be characterized by large resonance interactions. Similarly, some simple reactions that are commonly believed to be radical-free, such as [3 + 2] cycloadditions, are in fact governed by a high-lying biradical intermediate that helps to stabilize the transition state. More complex radical and enzymatic reactions can also be modelled, as illustrated by the example of horseradish peroxidase. These case studies show that computational analysis can complement experimental investigations and fill in the blanks to enable a more complete understanding of radical reactions.

scholarly journals Effect of Ionic Composition on Physicochemical Properties of Mono-Ether Functional Ionic Liquids

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3112
Author(s):  
Hancheng Zhou ◽  
Lifei Chen ◽  
Zhuo Wei ◽  
Yongjuan Lu ◽  
Cheng Peng ◽  
...  
Keyword(s):  
Ionic Liquids ◽  
Physicochemical Properties ◽  
Ionic Composition ◽  
Enzymatic Reactions ◽  
Exchange Reactions ◽  
Ether Group ◽  
Melt Temperature ◽  
Physiochemical Properties ◽  
Alkyl Substitution ◽  
Electrochemical Window

Tunable properties prompt the development of different “tailor-made” functional ionic liquids (FILs) for specific tasks. FILs with an ether group are good solvents for many organic compounds and enzymatic reactions. However, ionic composition influences the solubility by affecting the physiochemical properties of these FILs. To address the structure effect, a series of novel FILs with a mono-ether group (ME) based on imidazole were prepared through cationic functionalization and anionic exchange reactions, and characterized by NMR, mass spectroscopy, and Thermogravimetric analysis (TGA). The effect of ionic composition (cationic structure and anions) on density, viscosity, ionic conductivity, electrochemical window, and thermal properties of these ME-FILs were systematically investigated. In general, the viscosity and heat capacity increases with the bigger cationic volume of ME-FILs; in particular, the 2-alkyl substitution of imidazolium enhances the viscosity remarkably, whereas the density and conductivity decrease on the condition of the same [NTf2]− anion; For these ME-FILs with the same cations, the density follows the order of [NTf2]− > [PF6]− > [BF4]−. The viscosity follows the order of [PF6]− > [BF4]− > [NTf2]−. Ion conductivity follows the order of [NTf2]− ≈ [BF4]− > [PF6]−. It is noted that the dynamic density has a good linear relationship with the temperature, and the slopes are the same for all ME-FILs. Furthermore, these ME-FILs have broad electrochemical windows and glass transition temperatures in addition to a cold crystallization and a melt temperature for ME-FIL7. Therefore, the cationic structure and counter anion affect the physicochemical properties of these ME-FILs together.

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