Hydrogen bond dynamics and conformational flexibility in antipsychotics

Research output: Contribution to journalJournal articleResearchpeer-review

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Hydrogen bond dynamics and conformational flexibility in antipsychotics. / Pereira, Jose E M; Eckert, Juergen; Rudic, Svemir; Yu, Dehong; Mole, Richard; Tsapatsaris, Nikolaos; Bordallo, Heloisa N.

In: Physical chemistry chemical physics : PCCP, Vol. 21, No. 28, 17.07.2019, p. 15463-15470.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Pereira, JEM, Eckert, J, Rudic, S, Yu, D, Mole, R, Tsapatsaris, N & Bordallo, HN 2019, 'Hydrogen bond dynamics and conformational flexibility in antipsychotics', Physical chemistry chemical physics : PCCP, vol. 21, no. 28, pp. 15463-15470. https://doi.org/10.1039/c9cp02456e

APA

Pereira, J. E. M., Eckert, J., Rudic, S., Yu, D., Mole, R., Tsapatsaris, N., & Bordallo, H. N. (2019). Hydrogen bond dynamics and conformational flexibility in antipsychotics. Physical chemistry chemical physics : PCCP, 21(28), 15463-15470. https://doi.org/10.1039/c9cp02456e

Vancouver

Pereira JEM, Eckert J, Rudic S, Yu D, Mole R, Tsapatsaris N et al. Hydrogen bond dynamics and conformational flexibility in antipsychotics. Physical chemistry chemical physics : PCCP. 2019 Jul 17;21(28):15463-15470. https://doi.org/10.1039/c9cp02456e

Author

Pereira, Jose E M ; Eckert, Juergen ; Rudic, Svemir ; Yu, Dehong ; Mole, Richard ; Tsapatsaris, Nikolaos ; Bordallo, Heloisa N. / Hydrogen bond dynamics and conformational flexibility in antipsychotics. In: Physical chemistry chemical physics : PCCP. 2019 ; Vol. 21, No. 28. pp. 15463-15470.

Bibtex

@article{39ca4ac713644f4c98cc537f9593723e,
title = "Hydrogen bond dynamics and conformational flexibility in antipsychotics",
abstract = "Effective treatment of disorders of the central nervous system can often be achieved using bioactive molecules of similar moieties to those known to be tolerable. A better understanding of the solid-state characteristics of such molecules could thereby create new opportunities for research on pharmaceutical preparations and drug prescriptions, while information about their rich intramolecular dynamics may well add an important aspect in the field of in silico drug discovery. We have therefore investigated three different antipsychotic drugs: haloperidol (C21H23ClFNO2, HAL), aripiprazole (C23H27Cl2N3O2, APZ) and quetiapine hemifumarate (C21H25N3O2S·0.5C4H4O4, QTP) based on similarities either in their structures, hydrophobic and hydrophilic moieties, or in their modes of action, typical or atypical. Our aim was to test the structural and molecular stability of these three different antipsychotics. To this end, we compared the molecular vibrations observed by inelastic neutron spectroscopy of these systems with those from theoretical periodic calculations of the crystalline antipsychotics using the Vienna ab initio simulation package (VASP). While most of the observed features in the lattice region were reasonably well represented by the calculations, the overall spectra were relatively complex, and hence traditional assignment procedures for the approximately 600 normal modes in the unit cell were not possible. These results indicate that in the search for new drug candidates, not only analysis of the flexibility of the receptor, but also the dynamics of the active molecules play a role in improving the prediction of binding affinities.",
keywords = "Antipsychotic Agents/chemistry, Hydrogen Bonding, Molecular Conformation",
author = "Pereira, {Jose E M} and Juergen Eckert and Svemir Rudic and Dehong Yu and Richard Mole and Nikolaos Tsapatsaris and Bordallo, {Heloisa N}",
year = "2019",
month = "7",
day = "17",
doi = "10.1039/c9cp02456e",
language = "English",
volume = "21",
pages = "15463--15470",
journal = "Physical Chemistry Chemical Physics",
issn = "1463-9076",
publisher = "Royal Society of Chemistry",
number = "28",

}

RIS

TY - JOUR

T1 - Hydrogen bond dynamics and conformational flexibility in antipsychotics

AU - Pereira, Jose E M

AU - Eckert, Juergen

AU - Rudic, Svemir

AU - Yu, Dehong

AU - Mole, Richard

AU - Tsapatsaris, Nikolaos

AU - Bordallo, Heloisa N

PY - 2019/7/17

Y1 - 2019/7/17

N2 - Effective treatment of disorders of the central nervous system can often be achieved using bioactive molecules of similar moieties to those known to be tolerable. A better understanding of the solid-state characteristics of such molecules could thereby create new opportunities for research on pharmaceutical preparations and drug prescriptions, while information about their rich intramolecular dynamics may well add an important aspect in the field of in silico drug discovery. We have therefore investigated three different antipsychotic drugs: haloperidol (C21H23ClFNO2, HAL), aripiprazole (C23H27Cl2N3O2, APZ) and quetiapine hemifumarate (C21H25N3O2S·0.5C4H4O4, QTP) based on similarities either in their structures, hydrophobic and hydrophilic moieties, or in their modes of action, typical or atypical. Our aim was to test the structural and molecular stability of these three different antipsychotics. To this end, we compared the molecular vibrations observed by inelastic neutron spectroscopy of these systems with those from theoretical periodic calculations of the crystalline antipsychotics using the Vienna ab initio simulation package (VASP). While most of the observed features in the lattice region were reasonably well represented by the calculations, the overall spectra were relatively complex, and hence traditional assignment procedures for the approximately 600 normal modes in the unit cell were not possible. These results indicate that in the search for new drug candidates, not only analysis of the flexibility of the receptor, but also the dynamics of the active molecules play a role in improving the prediction of binding affinities.

AB - Effective treatment of disorders of the central nervous system can often be achieved using bioactive molecules of similar moieties to those known to be tolerable. A better understanding of the solid-state characteristics of such molecules could thereby create new opportunities for research on pharmaceutical preparations and drug prescriptions, while information about their rich intramolecular dynamics may well add an important aspect in the field of in silico drug discovery. We have therefore investigated three different antipsychotic drugs: haloperidol (C21H23ClFNO2, HAL), aripiprazole (C23H27Cl2N3O2, APZ) and quetiapine hemifumarate (C21H25N3O2S·0.5C4H4O4, QTP) based on similarities either in their structures, hydrophobic and hydrophilic moieties, or in their modes of action, typical or atypical. Our aim was to test the structural and molecular stability of these three different antipsychotics. To this end, we compared the molecular vibrations observed by inelastic neutron spectroscopy of these systems with those from theoretical periodic calculations of the crystalline antipsychotics using the Vienna ab initio simulation package (VASP). While most of the observed features in the lattice region were reasonably well represented by the calculations, the overall spectra were relatively complex, and hence traditional assignment procedures for the approximately 600 normal modes in the unit cell were not possible. These results indicate that in the search for new drug candidates, not only analysis of the flexibility of the receptor, but also the dynamics of the active molecules play a role in improving the prediction of binding affinities.

KW - Antipsychotic Agents/chemistry

KW - Hydrogen Bonding

KW - Molecular Conformation

U2 - 10.1039/c9cp02456e

DO - 10.1039/c9cp02456e

M3 - Journal article

VL - 21

SP - 15463

EP - 15470

JO - Physical Chemistry Chemical Physics

JF - Physical Chemistry Chemical Physics

SN - 1463-9076

IS - 28

ER -

ID: 225443114