Spatial and Temporal Resolution of the Oxygen-Independent Photoinduced DNA Interstrand Cross-Linking by a Nitroimidazole Derivative

Abdelgawwad, Abdelazim M. A.; Monari, Antonio; Tuñón, Iñaki; Francés‐Monerris, Antonio

doi:10.1021/acs.jcim.2c00460

Cited by 6 publications

(6 citation statements)

References 95 publications

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“…In LAC, photochemical and photophysical pathways different from the oxygen activation are exploited to disrupt the biological macrosystems and induce the cellular death. As an example, the presence of a suitable photoactivated leaving group in DNA interacting sensitizers , has been proposed as a way to induce covalent interstrand linkages, while Ruthenium complexes have been proposed for the controlled photorelease of reactive species. , …”

Section: Introductionmentioning

confidence: 99%

Perturbation of Lipid Bilayers by Biomimetic Photoswitches Based on Cyclocurcumin

Delova

Losantos

Pecourneau

et al. 2022

J. Chem. Inf. Model.

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The use of photoswitches which may be activated by suitable electromagnetic radiation is an attractive alternative to conventional photodynamic therapy. Here, we report all-atom molecular dynamics simulation of a biomimetic photoswitch derived from cyclocurcumin and experiencing E/Z photoisomerization. In particular, we show that the two isomers interact persistently with a lipid bilayer modeling a cellular membrane. Furthermore, the interaction with the membrane is strongly dependent on the concentration, and a transition between ordered and disordered arrangements of the photoswitches is observed. We also confirm that the structural parameters of the bilayer are differently affected by the two isomers and hence can be modulated through photoswitching, offering interesting perspectives for future applications.

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Section: Introductionmentioning

confidence: 99%

Perturbation of Lipid Bilayers by Biomimetic Photoswitches Based on Cyclocurcumin

Delova

Losantos

Pecourneau

et al. 2022

J. Chem. Inf. Model.

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“…To validate the TDDFT/B3LYP approach, the absorption properties of NBF-NO were computed by both the TDDFT/B3LYP protocol and by the multi-configurational complete-active-space second-order perturbation theory (CASPT2) method, as demonstrated in previous works on bioactive systems. , The nature of the electronic states and the comparison with the experimental records can be found in Table S1. The experimental lowest-energy band for NBF-NO (3.26 eV) is correctly reproduced by both methods with deviations from the experiment smaller than 0.2 eV in both cases (the intrinsic error of the method).…”

Section: Resultsmentioning

confidence: 99%

Red-Light-Photosensitized NO Release and Its Monitoring in Cancer Cells with Biodegradable Polymeric Nanoparticles

et al. 2023

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The role of nitric oxide (NO) as an "unconventional" therapeutic and the strict dependence of biological effects on its concentration require the generation of NO with precise spatiotemporal control. The development of precursors and strategies to activate NO release by excitation in the so-called "therapeutic window" with highly biocompatible and tissue-penetrating red light is desirable and challenging. Herein, we demonstrate that one-photon red-light excitation of Verteporfin, a clinically approved photosensitizer (PS) for photodynamic therapy, activates NO release, in a catalytic fashion, from an otherwise blue-light activatable NO photodonor (NOPD) with an improvement of about 300 nm toward longer and more biocompatible wavelengths. Steady-state and time-resolved spectroscopic and photochemical studies combined with theoretical calculations account for an NO photorelease photosensitized by the lowest triplet state of the PS. In view of biological applications, the water-insoluble PS and NOPD have been co-entrapped within water-dispersible, biodegradable polymeric nanoparticles (NPs) of mPEG-b-PCL (about 84 nm in diameter), where the red-light activation of NO release takes place even more effectively than in an organic solvent solution and almost independently by the presence of oxygen. Moreover, the ideal spectroscopic prerequisites and the restricted environment of the NPs permit the green-fluorescent co-product formed concomitantly to NO photorelease to communicate with the PS via Forster resonance energy transfer. This leads to an enhancement of the typical red emission of the PS offering the possibility of a double color optical reporter useful for the real-time monitoring of the NO release through fluorescence techniques. The suitability of this strategy applied to the polymeric NPs as potential nanotherapeutics was evaluated through biological tests performed by using HepG2 hepatocarcinoma and A375 melanoma cancer cell lines. Fluorescence investigation in cells and cell viability experiments demonstrates the occurrence of the NO release under onephoton red-light illumination also in the biological environment. This confirms that the adopted strategy provides a valuable tool for generating NO from an already available NOPD, otherwise activatable with the poorly biocompatible blue light, without requiring any chemical modification and the use of sophisticated irradiation sources.

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“…Molecular simulation as a powerful tool to probe the microscopic motions of different components in complex systems has been widely applied in various physical, chemical, and biological situations [ 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. In atomistic simulations of ILs, fixed-charge force fields are often employed due to the cell size required to eliminate finite-size artifacts and the time scale needed to thoroughly sample the configurational space of relevance.…”

Section: Introductionmentioning

confidence: 99%

Molecular Modelling of Ionic Liquids: Situations When Charge Scaling Seems Insufficient

et al. 2023

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Charge scaling as an effective solution to the experiment–computation disagreement in molecular modelling of ionic liquids (ILs) could bring the computational results close to the experimental reference for various thermodynamic properties. According to the large-scale benchmark calculations of mass density, solvation, and water-ILs transfer-free energies in our series of papers, the charge-scaling factor of 0.8 serves as a near-optimal option generally applicable to most ILs, although a system-dependent parameter adjustment could be attempted for further improved performance. However, there are situations in which such a charge-scaling treatment would fail. Namely, charge scaling cannot really affect the simulation outcome, or minimally perturbs the results that are still far from the experimental value. In such situations, the vdW radius as an additional adjustable parameter is commonly tuned to minimize the experiment–calculation deviation. In the current work, considering two ILs from the quinuclidinium family, we investigate the impacts of this vdW-scaling treatment on the mass density and the solvation/partition thermodynamics in a fashion similar to our previous charge-scaling works, i.e., scanning the vdW-scaling factor and computing physical properties under these parameter sets. It is observed that the mass density exhibits a linear response to the vdW-scaling factor with slopes close to −1.8 g/mL. By further investigating a set of physiochemically relevant temperatures between 288 K and 348 K, we confirm the robustness of the vdW-scaling treatment in the estimation of bulk properties. The best vdW-scaling parameter for mass density would worsen the computation of solvation/partition thermodynamics, and a marginal decrease in the vdW-scaling factor is considered as an intermediate option balancing the reproductions of bulk properties and solvation thermodynamics. These observations could be understood in a way similar to the charge-scaling situation. i.e., overfitting some properties (e.g., mass density) would degrade the accuracy of the other properties (e.g., solvation free energies). Following this principle, the general guideline for applying this vdW-tuning protocol is by using values between the density-derived choice and the solvation/partition-derived solution. The charge and current vdW scaling treatments cover commonly encountered ILs, completing the protocol for accurate modelling of ILs with fixed-charge force fields.

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Spatial and Temporal Resolution of the Oxygen-Independent Photoinduced DNA Interstrand Cross-Linking by a Nitroimidazole Derivative

Cited by 6 publications

References 95 publications

Perturbation of Lipid Bilayers by Biomimetic Photoswitches Based on Cyclocurcumin

Perturbation of Lipid Bilayers by Biomimetic Photoswitches Based on Cyclocurcumin

Red-Light-Photosensitized NO Release and Its Monitoring in Cancer Cells with Biodegradable Polymeric Nanoparticles

Molecular Modelling of Ionic Liquids: Situations When Charge Scaling Seems Insufficient

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