Structural stability of diclofenac vs. inhibition activity from ab initio molecular dynamics simulations. Comparative study with ibuprofen and ketoprofen

Kozłowska, Mariana; Rodziewicz, Paweł; Kaczmarek‐Kędziera, Anna

doi:10.1007/s11224-016-0893-8

Cited by 16 publications

(12 citation statements)

References 39 publications

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“…It has been previously shown by quantum dynamic tools that the great stabilizing role in acidic form of diclofenac is played by the intramolecular N-H...Cl interaction [53,54]. One of the local minima analyzed there correspond to the present DFH4 structure.…”

Section: Diclofenac Interaction With Single Pristine Chitosan Unitmentioning

confidence: 77%

Gas Phase Computational Study of Diclofenac Adsorption on Chitosan Materials

Kaczmarek‐Kędziera

2020

Molecules

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Environmental pollution with non-steroidal anti-inflammatory drugs and their metabolites exposes living organisms on their long-lasting, damaging influence. Hence, the ways of non-steroidal anti-inflammatory drugs (NSAIDs) removal from soils and wastewater is sought for. Among the potential adsorbents, biopolymers are employed for their good availability, biodegradability and low costs. The first available theoretical modeling study of the interactions of diclofenac with models of pristine chitosan and its modified chains is presented here. Supermolecular interaction energy in chitosan:drug complexes is compared with the the mutual attraction of the chitosan dimers. Supermolecular interaction energy for the chitosan-diclofenac complexes is significantly lower than the mutual interaction between two chitosan chains, suggesting that the diclofenac molecule will encounter problems when penetrating into the chitosan material. However, its surface adsorption is feasible due to a large number of hydrogen bond donors and acceptors both in biopolymer and in diclofenac. Modification of chitosan material introducing long-distanced amino groups significantly influences the intramolecular interactions within a single polymer chain, thus blocking the access of diclofenac to the biopolymer backbone. The strongest attraction between two chitosan chains with two long-distanced amino groups can exceed 120 kcal/mol, while the modified chitosan:diclofenac interaction remains of the order of 20 to 40 kcal/mol.

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Section: Diclofenac Interaction With Single Pristine Chitosan Unitmentioning

confidence: 77%

Gas Phase Computational Study of Diclofenac Adsorption on Chitosan Materials

Kaczmarek‐Kędziera

2020

Molecules

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“…The relative torsion of aromatic rings defined by the CCNC dihedral angle as well as the N─H…Cl interaction is also retained qualitatively, changing from 50.2° to 80.8° and from 2.422 to 2.707 å, respectively. All these values remain in the ranges determined by the previous study for the molecular dynamic simulations of global minimum of isolated DCL molecule . The table with the geometrical parameters is given in Supplementary Information.…”

Section: Structural Considerationsmentioning

confidence: 86%

“…All these values remain in the ranges determined by the previous study for the molecular dynamic simulations of global minimum of isolated DCL molecule. [62] The table with the geometrical parameters is given in Supplementary Information.…”

Section: Computational Detailsmentioning

confidence: 99%

Influence of photodegradation and surface modification on the graphene‐diclofenac physisorption process

Kaczmarek‐Kędziera

2019

Int J of Quantum Chemistry

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The present study provides the theoretical investigation of the mutual interaction of diclofenac and its photodegradation product with carbon materials. Because of the known weak interaction between graphene and aromatic molecules, the analyzed material surfaces are modified in order to maximize the mutual material: drug attraction. It is shown that the Stone‐Wales defects and single boron‐nitride pair doping only slightly influence the drug attraction, but the strongest impact is noticed for the introduction of the functional carboxyl group to the graphene sheet that preferably contains moreover single or double vacancies. Here, the additional stabilization with respect to the pristine graphene sheet is on the order of 7 to 10 kcal mol−1. A comparison of the adsorption of neutral acidic diclofenac molecule with its ionized form frequently applied in medical formulations shows that the negative charge accumulated on the carboxylate anion significantly increases the attraction of the drug by the graphene oxide (interaction energy changes from −27.45 to −46.33 kcal mol−1 upon ionization). Symmetry‐adapted perturbation theory applied for the decomposition of the interaction energy into the physically justified components confirms that all the investigated structures are governed by dispersion forces. Supermolecular MP2‐coupled approach with improved dispersion description allows to conclude that common density functional theory (DFT) functionals, including double hybrids with spin‐component scaling and dispersionless Pernal and Podeszwa functional, perform qualitatively well in the case of (modified‐) graphene materials, however, need to be applied with care for their boron‐nitride analogs.

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“…Mutual orientation of benzene rings might have a significant role in the COX-2 receptor inhibition. 54 According to ref ( 62 ), the structure of diclofenac, which is able to inhibit COX-2 (with the C–C–N–C dihedral angle of the −60°, see Figure 2 in ref ( 62 )), is not stable in the gas-phase ab initio simulations. In the case of MD simulations of water solutions, various C–C–N–C dihedral angles were observed (see Figure S6 ), including oscillations around −60°.…”

Section: Discussionmentioning

confidence: 99%

“…The intramolecular N–H···O bond and chlorine atoms present in the adjacent benzene ring ( Figure 1 and ref ( 62 )) cause the carboxylate group (−CO 2 – ) observed in the diclofenac anion (DN – ) to exhibit steric hindrance effect, which is characteristic of anti-inflammatory agents. 63 This distinguishes the DN – anion from the anions of carboxylic acids, the hydration of which has been studied in detail.…”

Section: Introductionmentioning

confidence: 99%

Hydration of the Carboxylate Group in Anti-Inflammatory Drugs: ATR-IR and Computational Studies of Aqueous Solution of Sodium Diclofenac

Levina

Penkov

Rodionova³

et al. 2018

ACS Omega

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Diclofenac (active ingredient of Voltaren) has a significant, multifaceted role in medicine, pharmacy, and biochemistry. Its physical properties and impact on biomolecular structures still attract essential scientific interest. However, its interaction with water has not been described yet at the molecular level. In the present study, we shed light on the interaction between the steric hindrance (the intramolecular N–H···O bond, etc.) carboxylate group (−CO2–) with water. Aqueous solution of sodium declofenac is investigated using attenuated total reflection-infrared (ATR-IR) and computational approaches, i.e., classical molecular dynamics (MD) simulations and density functional theory (DFT). Our coupled classical MD simulations, DFT calculations, and ATR-IR spectroscopy results indicated that the −CO2– group of the diclofenac anion undergoes strong specific interactions with the water molecules. The combined experimental and theoretical techniques provide significant insights into the spectroscopic manifestation of these interactions and the structure of the hydration shell of the −CO2– group. Moreover, the developed methodology for the theoretical analysis of the ATR-IR spectrum could serve as a template for the future IR/Raman studies of the strong interaction between the steric hindrance −CO2– group of bioactive molecules with the water molecules in dilute aqueous solutions.

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Structural stability of diclofenac vs. inhibition activity from ab initio molecular dynamics simulations. Comparative study with ibuprofen and ketoprofen

Cited by 16 publications

References 39 publications

Gas Phase Computational Study of Diclofenac Adsorption on Chitosan Materials

Gas Phase Computational Study of Diclofenac Adsorption on Chitosan Materials

Influence of photodegradation and surface modification on the graphene‐diclofenac physisorption process

Hydration of the Carboxylate Group in Anti-Inflammatory Drugs: ATR-IR and Computational Studies of Aqueous Solution of Sodium Diclofenac

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