Absorption behavior of doxorubicin hydrochloride in visible region in different environments: a combined experimental and computational study

Abstract

The experimental absorption measurements in the interval 350-600 nm (Vis), molecular dynamics simulations, quantum-mechanics calculations and an advanced molecular treatment of simulation data are here combined to provide a complete...

Effects of Environmental and Electric Perturbations on the pKa of Thioredoxin Cysteine 35: A Computational Study

“…The Perturbed Matrix Method [ 16 , 17 , 18 , 19 ], is a hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) approach [ 20 , 21 ] that combines, with a low computational cost, an accurate description of the system region of interest—defined as Quantum Center (QC)—with a classical treatment of the surrounding environment, as provided by Molecular Dynamics (MD) simulations. The PMM-MD method has already demonstrated its validity for the characterization and modelling of biological systems [ 18 , 19 , 22 , 23 , 24 , 25 ]. In this work, it is used for the description of the deprotonation reaction and the calculation of pKa of Cysteine residues in a protein environment.…”

PyMM: An Open-Source Python Program for QM/MM Simulations Based on the Perturbed Matrix Method

“…To show the capabilities of PyMM, we describe its application to two molecules in solution, doxorubicin (DX) and deoxyguanosine. The application of the PyMM to doxorubicin allowed us to model its perturbed electronic excited states and to accurately predict its absorption spectrum in water, whereas for the deoxyguanosine, we applied the PyMM to estimate the oxidation free energy (i.e., the oxidation potential) in solution . Note that in the test set included in the code, we also provide the data to evaluate the absorption spectrum of water by means of PyMM. , …”

“…By means of MD-PMM, it is possible to calculate the UV−vis absorption spectra in liquid-state systems. 4,6,30 In the case of a chromophore in solution that exhibits negligible vibronic transitions (i.e., vanishing vibrational overlap between ground to excited states) compared to the vertical one or when the vibronic vertical signal is broad enough to cover all of the other non-negligible vibronic transitions, the electronic vertical transition can provide a good approximation of the overall vibronic lineshape. 31,32 The absorption spectrum of a chromophore in liquid-state system can be expressed through the extinction coefficient ε 0,i (ν) for the 0 → i electronic transition, which can be calculated as follows h c ( ) ( )…”

“…QM/MM methods established themselves as one of the primary tools to model biological systems, combining accuracy and computational efficiency. , The perturbed matrix method (PMM) − is a relatively recent QM/MM method that was developed with the aim of reducing the computing time necessary for this kind of calculation, making it suitable for application to complex systems, ranging from simple molecules in solution to protein–DNA complexes. PMM has been successfully applied to reproduce different properties such as the UV–vis spectra, ,, fluorescence spectra, circular dichroism spectra, IR spectra, , and redox potentials. , The method adopts an a posteriori strategy, i.e., the effect of the perturbation on the QM region of interest, typically evaluated from a classical molecular dynamics, is evaluated for every configuration at a very limited computational cost. Such an approach usually requires few quantum mechanical calculations (for a rigid QM region requiring a single calculation), effectively making the time scale of the PMM simulations on par with classical MD simulations for large systems and long trajectories.…”

Complexation and organization of doxorubicin on polystyrene sulfonate chains: impacts on doxorubicin dimerization and quenching

“…Another interesting feature of DX is the dependence of its electronic excited states from the environment. 13 For example, the ratio of the intensities of the first ( λ 1 ≃ 560 nm) and second ( λ 2 ≃ 590 nm) bands of the fluorescence emission spectrum ( I 1 and I 2 , respectively) changes in solvents of different polarities. This ratio can indeed be used to empirically evaluate the polarity of the molecular environment surrounding the drug.…”