Structural/Physicochemical Properties of Corycavidine, a Key Intermetabolite in the Biosynthesis of Isoquinoline Alkaloids, Elucidated by X-Ray Crystallography, Solution Conformation and Thermal Behavior Analyses, and Energy Calculations

2000 ◽  
Vol 73 (5) ◽  
pp. 1233-1241 ◽  
Author(s):  
Miyoko Kamigauchi ◽  
Mayumi Yoshida ◽  
Kayoko Saiki ◽  
Makiko Sugiura ◽  
Jujiro Nishijo ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Thermal Behavior ◽  
Isoquinoline Alkaloids ◽  
Solution Conformation ◽  
Energy Calculations ◽  
X Ray ◽  
X Ray Crystallography

Physicochemical Properties of Crystalline Forms of Ethynylestradiol Solvates: Comparison of Thermal Behavior with X-ray Crystal Structure

1989 ◽  
Vol 78 (4) ◽  
pp. 274-280 ◽  
Author(s):  
Toshimasa Ishida ◽  
Mitsunobu Doi ◽  
Mari Shimamoto ◽  
Naoko Minamino ◽  
Katsumi Nonaka ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Physicochemical Properties ◽  
Thermal Behavior ◽  
X Ray ◽  
Crystalline Forms

scholarly journals X-Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists

2019 ◽  
Author(s):  
Willem Jespers ◽  
Grégory Verdon ◽  
Jhonny Azuaje ◽  
maria majellaro ◽  
Henrik Keränen ◽  
...  
Keyword(s):  
Free Energy ◽  
Adenosine Receptor ◽  
Free Energy Calculations ◽  
Binding Modes ◽  
A2a Adenosine Receptor ◽  
Binding Model ◽  
Energy Calculations ◽  
X Ray ◽  
X Ray Crystallography ◽  
Pharmacological Data

<div> <div> <div> <p>Nowadays, rigorous free energy calculations are routinely considered in pharmaceutical design strategies. One typical sce- nario is the lead-optimization based on well-defined protein-ligand binding modes, inferred by pharmacological data in com- putational models and ultimately revealed by structural data. In this work, we reveal the molecular determinants of antago- nist binding to the adenosine A2A adenosine receptor (AR), an emerging target in immuno-oncology, via a robust protocol that connects structural and pharmacological data through free energy perturbation (FEP) calculations. Eight A2AAR binding site mutations from biophysical mapping experiments were initially analyzed with FEP simulations of each side-chain mutation, performed on alternate binding modes previously proposed in the literature. The results strongly suggested that only one binding mode could explain this experimental data, which was used to subsequently design a series of 11 chromone deriva- tives. The experimental affinities of these new compounds were linked through a cycle of ligand-FEP calculations around selected ligand pairs, which allowed the identification of the optimal positioning of the different chemical substituents in the proposed binding model. Subsequent X-ray crystallography of the A2AAR with a low and high affinity chromone derivative confirmed the predicted binding orientation, and provided new insights in the role of the explored substituents in the chro- </p> </div> </div> <div> <div> <p>mone scaffold. </p> </div> </div> </div>

scholarly journals X‐Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A 2A Adenosine Receptor Antagonists

2020 ◽  
Vol 59 (38) ◽  
pp. 16536-16543 ◽  
Author(s):  
Willem Jespers ◽  
Grégory Verdon ◽  
Jhonny Azuaje ◽  
Maria Majellaro ◽  
Henrik Keränen ◽  
...  
Keyword(s):  
Free Energy ◽  
Adenosine Receptor ◽  
Free Energy Calculations ◽  
Binding Mechanism ◽  
Receptor Antagonists ◽  
Energy Calculations ◽  
X Ray ◽  
X Ray Crystallography

scholarly journals X-Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists

2019 ◽  
Author(s):  
Willem Jespers ◽  
Grégory Verdon ◽  
Jhonny Azuaje ◽  
maria majellaro ◽  
Henrik Keränen ◽  
...  
Keyword(s):  
Free Energy ◽  
Adenosine Receptor ◽  
Free Energy Calculations ◽  
Binding Modes ◽  
A2a Adenosine Receptor ◽  
Binding Model ◽  
Energy Calculations ◽  
X Ray ◽  
X Ray Crystallography ◽  
Pharmacological Data

<div> <div> <div> <p>Nowadays, rigorous free energy calculations are routinely considered in pharmaceutical design strategies. One typical sce- nario is the lead-optimization based on well-defined protein-ligand binding modes, inferred by pharmacological data in com- putational models and ultimately revealed by structural data. In this work, we reveal the molecular determinants of antago- nist binding to the adenosine A2A adenosine receptor (AR), an emerging target in immuno-oncology, via a robust protocol that connects structural and pharmacological data through free energy perturbation (FEP) calculations. Eight A2AAR binding site mutations from biophysical mapping experiments were initially analyzed with FEP simulations of each side-chain mutation, performed on alternate binding modes previously proposed in the literature. The results strongly suggested that only one binding mode could explain this experimental data, which was used to subsequently design a series of 11 chromone deriva- tives. The experimental affinities of these new compounds were linked through a cycle of ligand-FEP calculations around selected ligand pairs, which allowed the identification of the optimal positioning of the different chemical substituents in the proposed binding model. Subsequent X-ray crystallography of the A2AAR with a low and high affinity chromone derivative confirmed the predicted binding orientation, and provided new insights in the role of the explored substituents in the chro- </p> </div> </div> <div> <div> <p>mone scaffold. </p> </div> </div> </div>

scholarly journals Special Issue Editorial: Chemical Bonding in Crystals and Their Properties

Crystals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 194
Author(s):  
Anna V. Vologzhanina ◽  
Yulia V. Nelyubina
Keyword(s):  
Physicochemical Properties ◽  
Chemical Bonding ◽  
Chemical Compounds ◽  
Special Issue ◽  
Crystalline Materials ◽  
X Ray ◽  
X Ray Crystallography ◽  
Invaluable Tool ◽  
Successful Design

Relations between physicochemical properties of chemical compounds exploited in many modern applications (including optical, magnetic, electrical, mechanical, and others) and interatomic interactions that operate in their crystals are the key to the successful design of new crystalline materials, in which X-ray crystallography has proved to be an invaluable tool [...]

2,2',4,4',6,6'-Hexanitrobiphenyl-3,3',5,5'-Tetramine: Synthesis and Comparison of Physicochemical Properties With Those of Other Amino Nitro Biphenyls

1987 ◽  
Vol 40 (1) ◽  
pp. 175 ◽  
Author(s):  
AJ Bell ◽  
E Eadie ◽  
RW Read ◽  
BW Skelton ◽  
AH White
Keyword(s):  
Thermal Stability ◽  
Thermal Properties ◽  
Physicochemical Properties ◽  
Chemical Stability ◽  
Amino Groups ◽  
X Ray ◽  
X Ray Crystallography ◽  
Spectroscopic Characteristics ◽  
Impact Energies ◽  
Present Understanding

A synthesis of 2,2′,4,4′,6,6′-hexanitrobiphenyl-3,3′,5,5′-tetramine, the most highly aminated of a series of hexanitrobiphenyl explosives, is described, and its physical and spectroscopic characteristics determined. The thermal properties and impact sensitiveness of the explosive have been studied, and the substance has been found to be relatively unstable to heat and more sensitive to impact than expected by comparison with other aminated polynitroaromatic compounds. Evidence is provided which suggests that, contrary to present understanding, the introduction of amino groups into such nitroaromatics may decrease their thermal stability and lower their chemical stability sufficiently to allow partial decomposition at low impact energies. �The structure of the tetramine has been determined by X-ray crystallography, and the features likely to be responsible for the unexpected physicochemical properties of the tetramine are discussed based on this.

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