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Theoretical assessment of naphazoline redoxchemistry and photochemistry
Örebro University, Department of Natural Sciences. (Biophysical Chemistry)
Örebro University, Department of Natural Sciences. (Biophysical Chemistry)
2007 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 111, no 15, p. 3977-3981Article in journal (Refereed) Published
Abstract [en]

The imidazoline derivative naphazoline (2-(1-naphtylmethyl)-2-imidazoline) is an α2-adrenergic agonist used as non-prescription eye and nasal preparations. Besides its functionality in generating vascoconstriction and decongestion in the patient, the toxicity, ROS generating capability, and recently also possible antioxidant capacity of the compound have been reported in the literature. In the current work the structural and electronic features of the drug are explored, using computational chemical tools. Electron affinities, ionization potentials, and excitation energies are reported, as well as charge and spin distributions of various forms of the drug. The difference in photochemical behavior between the protonated and unprotonated (basic) species is explained by the molecular orbital distributions, allowing for efficient excitation quenching in the basic structure but clear naphthalene to imidazolene charge transfer upon HOMO→ LUMO excitation in the protonated form, enabling larger intersystem crossing capability to the imidazole localized excited triplet and a resulting higher singlet oxygen quantum yield.

Place, publisher, year, edition, pages
Washington, DC: American Chemical Society , 2007. Vol. 111, no 15, p. 3977-3981
Keywords [en]
Molecular Structure, Naphazoline, Oxidation-Reduction, Photochemistry, Density functional theory
National Category
Theoretical Chemistry Natural Sciences Chemical Sciences
Research subject
Chemistry
Identifiers
URN: urn:nbn:se:oru:diva-4105DOI: 10.1021/jp070207fPubMedID: 17388561OAI: oai:DiVA.org:oru-4105DiVA, id: diva2:138404
Available from: 2007-11-02 Created: 2007-11-02 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Computational studies of photodynamic drugs, phototoxic reactions and drug design
Open this publication in new window or tab >>Computational studies of photodynamic drugs, phototoxic reactions and drug design
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The most important criterion when designing new drugs or improving old ones in order to prevent side effects or at least diminish them is drug safety. Treatment of all diseases generally needs use of either topical application or systemic medications (transported in the blood) during a certain period of time. These treatments are associated with a number of adverse effects. Photosensitivity is one of those side effects, with phototoxicity as one of the photosensitivity disorders. This adverse side effect arises because of a reaction between UV or visible-light and the drug molecule, its active form or photoproduct(s). Due to phototoxic side effect, unexpected symptoms varying from just a simple rash to severe cutaneous affectations can appear. Furthermore, biomolecular damage occurs once the drug-light interaction takes place persistently and ends with cell death.

Several drug families, such as over-the-counter drugs in the non-steroidal anti-inflammatory drug family of 2-arylpropionic acid derivatives, or prescription required fluoroquinolone drugs, have the capability to absorb mainly UV light radiation which in turn causes different phototoxic reactions by forming radical derivatives, reactive oxygen species or both. These may effect DNA, protein and lipid cell components leading to photogenotoxicity, photoallergy and lipid peroxidation, respectively. The photodegradation mechanisms of drugs belonging to the above mentioned families including ketoprofen, ibuprofen, flurbiprofen, naproxen, the active form of nabumetone, diclofenac and its main photoproduct, suprofen, tiaprofenic acid, naphazoline, norfloxacin and lomefloxacin are investigated in more detail in this thesis.

The results obtained by computational density functional theory (DFT) and time-dependent-DFT (TD-DFT) are in line with experimental data available to date. The studies provide detailed insight into the molecular basis and understanding of the full photodegradation mechanisms of drugs mentioned above. This also plays an important role in preventing or at least reducing the phototoxic adverse effects by enabling the development of safe drugs in this area. Hence, new modified non-steroid anti-inflammatory molecules were designed by computational techniques. Obtained results suggest possibility of their future usage as pharmaceuticals with reduced photodegradation and cyclooxygenase 1 induced adverse side effects compared to the parent compounds.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2009. p. 99
Series
Örebro Studies in Life Science ; 4
Keywords
NSAIDs, fluoroquinolone, photodegradation, phototoxicity, drug design, DFT, TD-DFT
National Category
Physical Chemistry
Research subject
Chemistry
Identifiers
urn:nbn:se:oru:diva-8356 (URN)978-91-7668-694-2 (ISBN)
Public defence
2009-11-26, Hörsal M, Örebro universitet, Örebro, 13:15 (English)
Opponent
Supervisors
Available from: 2009-10-26 Created: 2009-10-26 Last updated: 2017-10-18Bibliographically approved

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Musa, Klefah A. K.Eriksson, Leif A.

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