scholarly journals Synthesis, Kinetic and Conformational Studies of 2-Substituted-5-(β-d-glucopyranosyl)-pyrimidin-4-ones as Potential Inhibitors of Glycogen Phosphorylase

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5463
Author(s):  
Konstantinos F. Mavreas ◽  
Dionysios D. Neofytos ◽  
Evangelia D. Chrysina ◽  
Alessandro Venturini ◽  
Thanasis Gimisis
Keyword(s):  
Density Functional ◽  
Glycogen Phosphorylase ◽  
Density Functional Theory Calculations ◽  
Rabbit Muscle ◽  
Functional Theory ◽  
Design And Synthesis ◽  
Potential Inhibitors ◽  
New Compounds ◽  
General Synthesis

Dysregulation of glycogen phosphorylase, an enzyme involved in glucose homeostasis, may lead to a number of pathological states such as type 2 diabetes and cancer, making it an important molecular target for the development of new forms of pharmaceutical intervention. Based on our previous work on the design and synthesis of 4-arylamino-1-(β-d-glucopyranosyl)pyrimidin-2-ones, which inhibit the activity of glycogen phosphorylase by binding at its catalytic site, we report herein a general synthesis of 2-substituted-5-(β-d-glucopyranosyl)pyrimidin-4-ones, a related class of metabolically stable, C-glucosyl-based, analogues. The synthetic development consists of a metallated heterocycle, produced from 5-bromo-2-methylthiouracil, in addition to protected d-gluconolactone, followed by organosilane reduction. The methylthio handle allowed derivatization through hydrolysis, ammonolysis and arylamine substitution, and the new compounds were found to be potent (μM) inhibitors of rabbit muscle glycogen phosphorylase. The results were interpreted with the help of density functional theory calculations and conformational analysis and were compared with previous findings.

scholarly journals Computationally aided, entropy-driven synthesis of highly efficient and durable multi-elemental alloy catalysts

2020 ◽  
Vol 6 (11) ◽  
pp. eaaz0510 ◽  
Author(s):  
Yonggang Yao ◽  
Zhenyu Liu ◽  
Pengfei Xie ◽  
Zhennan Huang ◽  
Tangyuan Li ◽  
...  
Keyword(s):  
Density Functional ◽  
Rational Design ◽  
Density Functional Theory Calculations ◽  
Great Promise ◽  
Alloy Formation ◽  
Functional Theory ◽  
Excellent Thermal Stability ◽  
Design And Synthesis ◽  
Highly Efficient ◽  
Computational Strategy

Multi-elemental alloy nanoparticles (MEA-NPs) hold great promise for catalyst discovery in a virtually unlimited compositional space. However, rational and controllable synthesize of these intrinsically complex structures remains a challenge. Here, we report the computationally aided, entropy-driven design and synthesis of highly efficient and durable catalyst MEA-NPs. The computational strategy includes prescreening of millions of compositions, prediction of alloy formation by density functional theory calculations, and examination of structural stability by a hybrid Monte Carlo and molecular dynamics method. Selected compositions can be efficiently and rapidly synthesized at high temperature (e.g., 1500 K, 0.5 s) with excellent thermal stability. We applied these MEA-NPs for catalytic NH3 decomposition and observed outstanding performance due to the synergistic effect of multi-elemental mixing, their small size, and the alloy phase. We anticipate that the computationally aided rational design and rapid synthesis of MEA-NPs are broadly applicable for various catalytic reactions and will accelerate material discovery.

Design and synthesis of new Ru-complexes as potential photo-sensitizers: experimental and TD-DFT insights

RSC Advances ◽  
2016 ◽  
Vol 6 (73) ◽  
pp. 69647-69657 ◽  
Author(s):  
Walid Sharmoukh Walid Sharmoukh ◽  
Walid M. I. Hassan ◽  
Philippe C. Gros ◽  
Nageh K. Allam
Keyword(s):  
Density Functional Theory ◽  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Functional Theory ◽  
Design And Synthesis ◽  
Td Dft ◽  
Ru Complexes

Design of photosensitizers aided by density functional theory calculations.

The structures of xenorine A–C from the entomopathogenic bacterium Xenorhabdus indica

2017 ◽  
Vol 41 (5) ◽  
pp. 262-265
Author(s):  
Lie-Feng Ma ◽  
Hao-Ying Qian ◽  
Yang Zheng ◽  
Wei-Wei Pang ◽  
Yuan-Yuan Li ◽  
...  
Keyword(s):  
Quantum Chemical ◽  
Density Functional ◽  
Density Functional Theory Calculations ◽  
2D Nmr ◽  
Immunosuppressive Activity ◽  
Functional Theory ◽  
Chemical Structures ◽  
Synthetic Product ◽  
New Compounds

Three new compounds, xenorine A-C, along with six known compounds were isolated from the cultured broth of Xenorhabdus indica. The chemical structures of these compounds were elucidated mainly by analysis of 1D and 2D NMR and MS data. The major metabolites were dioxopiperazines. In addition, 5,6,11,11a-tetrahydro-1 H-imidazo[1′,5′:1,6]pyrido[3,4- b]indole-1,3(2 H)-dione, previously described as synthetic product, was isolated as a natural product. The absolute configuration was determined using quantum chemical time-dependent density functional theory calculations. The six known compounds showed weak in vitro immunosuppressive activity towards concanavalin-A- and lipopolysaccharide -induced proliferation of mice splenocytes.

On the Linear Geometry of Lanthanide Hydroxide (Ln—OH, Ln=La-Lu)

2019 ◽  
Author(s):  
Hassan Harb ◽  
Lee Thompson ◽  
Hrant Hratchian
Keyword(s):  
Triple Bond ◽  
Density Functional ◽  
Valence Electron ◽  
Density Functional Theory Calculations ◽  
Electron Configuration ◽  
Functional Theory ◽  
Key Species ◽  
Pi Orbitals ◽  
Lanthanide Hydroxide ◽  
Linear Geometry

Lanthanide hydroxides are key species in a variety of catalytic processes and in the preparation of corresponding oxides. This work explores the fundamental structure and bonding of the simplest lanthanide hydroxide, LnOH (Ln=La-Lu), using density functional theory calculations. Interestingly, the calculations predict that all structures of this series will be linear. Furthermore, these results indicate a valence electron configuration featuring an occupied sigma orbital and two occupied pi orbitals for all LnOH compounds, suggesting that the lanthanide-hydroxide bond is best characterized as a covalent triple bond.

On the Linear Geometry of Lanthanide Hydroxide (Ln—OH, Ln=La-Lu)

2019 ◽  
Author(s):  
Hassan Harb ◽  
Lee Thompson ◽  
Hrant Hratchian
Keyword(s):  
Triple Bond ◽  
Density Functional ◽  
Valence Electron ◽  
Density Functional Theory Calculations ◽  
Electron Configuration ◽  
Functional Theory ◽  
Key Species ◽  
Pi Orbitals ◽  
Lanthanide Hydroxide ◽  
Linear Geometry

Lanthanide hydroxides are key species in a variety of catalytic processes and in the preparation of corresponding oxides. This work explores the fundamental structure and bonding of the simplest lanthanide hydroxide, LnOH (Ln=La-Lu), using density functional theory calculations. Interestingly, the calculations predict that all structures of this series will be linear. Furthermore, these results indicate a valence electron configuration featuring an occupied sigma orbital and two occupied pi orbitals for all LnOH compounds, suggesting that the lanthanide-hydroxide bond is best characterized as a covalent triple bond.

A New Interpretation of the Structure and Solvent Dependence of the Far UV Circular Dichroism Spectrum of Short Oligopeptides

2019 ◽  
Author(s):  
Anshuman Kumar ◽  
Reinhard Schweitzer-Stenner ◽  
Bryan Wong
Keyword(s):  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Cd Spectra ◽  
Functional Theory ◽  
Polyproline Ii ◽  
Solvent Dependence ◽  
Explicit Consideration ◽  
New Interpretation ◽  
Implicit And Explicit ◽  
Explicit Water

In this work, we carry out new time-dependent density functional theory calculations on the cationic tripeptide GAG in implicit and explicit water to determine the transitions that give rise to the observed CD signals of polyproline II and β-strand conformations. Our results reveal a plethora of electronic transitions that are governed by configurational interactions between multiple molecular orbital transitions of comparable energy. We also show that reproducing the CD spectra of polyproline II and β-strand conformations requires the explicit consideration of water molecules. The structure dependence of delocalized occupied orbitals contributes to the experimentally-observed invalidation of Flory’s isolated pair hypothesis.

A New Interpretation of the Structure and Solvent Dependence of the Far UV Circular Dichroism Spectrum of Short Oligopeptides

2019 ◽  
Author(s):  
Anshuman Kumar ◽  
Reinhard Schweitzer-Stenner ◽  
Bryan Wong
Keyword(s):  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Cd Spectra ◽  
Functional Theory ◽  
Polyproline Ii ◽  
Solvent Dependence ◽  
Explicit Consideration ◽  
New Interpretation ◽  
Implicit And Explicit ◽  
Explicit Water

In this work, we carry out new time-dependent density functional theory calculations on the cationic tripeptide GAG in implicit and explicit water to determine the transitions that give rise to the observed CD signals of polyproline II and β-strand conformations. Our results reveal a plethora of electronic transitions that are governed by configurational interactions between multiple molecular orbital transitions of comparable energy. We also show that reproducing the CD spectra of polyproline II and β-strand conformations requires the explicit consideration of water molecules. The structure dependence of delocalized occupied orbitals contributes to the experimentally-observed invalidation of Flory’s isolated pair hypothesis.

Is a Non-Transition Element Nitride Ferromagnet Ever Achievable? Indication of the N-N Pairing Instability

2006 ◽  
Vol 71 (11-12) ◽  
pp. 1525-1531 ◽  
Author(s):  
Wojciech Grochala
Keyword(s):  
Density Functional Theory ◽  
Density Functional ◽  
Transition Element ◽  
Density Functional Theory Calculations ◽  
Functional Theory

The enthalpy of four polymorphs of CaN has been scrutinized at 0 and 100 GPa using density functional theory calculations. It is shown that structures of diamagnetic calcium diazenide (Ca2N2) are preferred over the cubic ferromagnetic polymorph (CaN) postulated before, both at 0 and 100 GPa.

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