Correct Modeling of Cisplatin: a Paradigmatic Case

Tasinato, Nicola; Puzzarini, Cristina; Barone, Vincenzo

doi:10.1002/anie.201707683

Cited by 28 publications

(38 citation statements)

References 22 publications

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“…Density functional calculations along with molecular modelling have been used for the geometry optimizations of platinum and other heavy transition metal complexes and also to predict and explain their biological properties . In the present study, DFT modelling was performed on various mono‐ and bifunctional adducts of 1,1/ t,t and 1,0,1/ t,t,t with DHPA.…”

Section: Resultsmentioning

confidence: 99%

Structural Factors Affecting Binding of Platinum Anticancer Agents with Phospholipids: Influence of Charge and Phosphate Clamp Formation

Gorle

Zhang

Liu

et al. 2018

Chemistry A European J

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We report a detailed NMR and DFT study of the interaction of polynuclear platinum anticancer agents (PPCs) with negatively charged phospholipids as a mechanism for their cellular uptake. The reactions of fully N-labelled [{trans-PtCl(NH ) } (μ-trans-Pt(NH ) {NH (CH ) NH } )] ( N-1, 1,0,1/t,t,t) and the dinuclear [{trans-PtCl(NH ) } {μ-H N(CH ) NH }] ( N-2, 1,1/t,t) with the sodium salt of 1,2-dihexanoyl-sn-glycero-3-phosphate (DHPA) were studied at 298 K, pH ≈5.4, by [ H, N] HSQC 2D NMR spectroscopy. Both N-1 and N-2 form an initial mono-adduct in which the DHPA is coordinated via the phosphate O atom. For the dinuclear N-2, coordination of a second DHPA, in two different orientations, leads to two conformers of the bifunctional adduct. For N-1, coordination of the second DHPA allows the central {PtN } coordination unit to bind electrostatically to two additional DHPA molecules via phosphate clamp interactions, in an extended network. For both 1,0,1/t,t,t (1) and 1,1/t,t (2), equilibrium conditions are obtained more slowly (>35 h) than in the presence of phosphate (12 h) and in each case the rate constant for the first step of DHPA binding (k ) is about 8 times higher than that for phosphate, whereas the rate constants for the reverse reactions are quite similar. Reaction of N-1 with the sodium salt of 1,2-dihexanoyl-sn-glycero-3-[phosphatidyl-l-serine] (DHPS) showed only minor adduct formation via coordination to the N-donor atom of the phosphoserine group.

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Section: Resultsmentioning

confidence: 99%

Structural Factors Affecting Binding of Platinum Anticancer Agents with Phospholipids: Influence of Charge and Phosphate Clamp Formation

Gorle

Zhang

Liu

et al. 2018

Chemistry A European J

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“…The rev-DSD-PBEP86 double-hybrid density functional, recently proposed by Martin and coworkers (Santra et al, 2019), was employed together with the aug-cc-pVTZ and jun-cc-pVTZ basis sets. Indeed, triple-ζ basis sets in conjunction with the B2PLYP double-hybrid functional (Grimme, 2006) have been demonstrated to provide accurate predictions of geometries, rotational spectroscopic parameters and vibrational properties (Biczysko et al, 2010;Penocchio et al, 2015;Spada et al, 2017b;Tasinato et al, 2017;Boussessi et al, 2020a,b). Both PW6B95 and rev-DSD-PBEP86 were augmented for dispersion correlation through the Grimme's DFT-D3 scheme (Grimme et al, 2010) with Becke-Johnson damping (Grimme et al, 2011), even if the bare PW6B95 functional can already provide a satisfactory description of dispersion forces (Tasinato and Grimme, 2015).…”

Section: Computational Methodologymentioning

confidence: 99%

Accuracy Meets Interpretability for Computational Spectroscopy by Means of Hybrid and Double-Hybrid Functionals

et al. 2020

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Accuracy and interpretability are often seen as the devil and holy grail in computational spectroscopy and their reconciliation remains a primary research goal. In the last few decades, density functional theory has revolutionized the situation, paving the way to reliable yet effective models for medium size molecules, which could also be profitably used by non-specialists. In this contribution we will compare the results of some widely used hybrid and double hybrid functionals with the aim of defining the most suitable recipe for all the spectroscopic parameters of interest in rotational and vibrational spectroscopy, going beyond the rigid rotor/harmonic oscillator model. We will show that last-generation hybrid and double hybrid functionals in conjunction with partially augmented double-and triple-zeta basis sets can offer, in the framework of second order vibrational perturbation theory, a general, robust, and user-friendly tool with unprecedented accuracy for medium-size semi-rigid molecules.

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“…Throughout this work, we use the vibrational assignment published in several studies. [4,5,8,9] From the practical viewpoint, the most important step of cisplatin usage is the formation of different platinum complexes in physiological environment. [10] It is generally accepted that chloride ligands are replaced by water molecules in the coordination sphere of Pt(II) when cisplatin reaches cytoplasm (containing approximately 4-10mM chloride concentration, instead of 154mM Cl − in extracellular environment).…”

Section: Introductionmentioning

confidence: 99%

“…The structural parameters and vibrational results predicted by the calculations were compared with the corresponding experimental data, and a complete assignment of the cisplatin vibrational spectra was presented in Amado et al and Georgieva et al Later theoretical calculations of cisplatin vibrational modes were published in several studies . Quantum chemical calculations of cisplatin were discussed as a correct modeling approach in Tasinato et al The most recent study of the optimized structures and lowest energy conformations of five currently used platinum‐based drugs (cisplatin, carboplatin, nedaplatin, oxaliplatin, and heptaplatin) has focused on the low‐energy modes between 200 and 600 cm −1 , where anharmonicity effects have less influence on the accuracy of computed frequencies. Throughout this work, we use the vibrational assignment published in several studies …”

Section: Introductionmentioning

confidence: 99%

“…Quantum chemical calculations of cisplatin were discussed as a correct modeling approach in Tasinato et al The most recent study of the optimized structures and lowest energy conformations of five currently used platinum‐based drugs (cisplatin, carboplatin, nedaplatin, oxaliplatin, and heptaplatin) has focused on the low‐energy modes between 200 and 600 cm −1 , where anharmonicity effects have less influence on the accuracy of computed frequencies. Throughout this work, we use the vibrational assignment published in several studies .…”

Section: Introductionmentioning

confidence: 99%

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Cisplatin interacting with buffering media and cysteine: Molecular insight due to Raman microspectroscopy

Šišková

2019

J Raman Spectroscopy

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The solvation of cisplatin, [Pt(NH3)2Cl2], a widely used chemotherapeutical drug, regarded on molecular level in model media is often overlooked by researchers. It is, however, essential in several aspects. The solvation was monitored by using Raman scattering microspectroscopy. This technique being used for the first time enables us to focus the laser beam several micrometers above the dissolving crystals of cisplatin, allowing to monitor the process of cisplatin dissolution in situ. The obtained Raman microspectroscopic results provided a direct qualitative evidence about (a) interaction between Tris, MOPS, and HEPES buffers and cisplatin via PtN coordination covalent bond and (b) interaction of cisplatin with cysteine dominantly through PtS bond (at pH 7.4). Furthermore, this vibrational spectroscopic technique revealed a decreased dissolution of cisplatin in a particular buffering solution in the presence of NaCl abundance; kinetics of the PtN formation in the case of MOPS–NaCl medium was monitored. Moreover, spatial dissolution of cisplatin in Cys‐Tris medium was observed in situ. The particular buffering medium, containing either primary or tertiary amines, can interact with cisplatin via a coordination covalent bond. The presence of an increased NaCl concentration can partially suppress this interaction. Raman microspectroscopy, a method of vibrational spectroscopy, is a powerful technique to investigate the dissolution of cisplatin in situ. On the basis of vibrational microspectroscopic measurements, it provides direct evidence about cisplatin interactions with selected model media being widely used in biochemistry and biophysics. This interaction could influence the effectiveness of cisplatin as a drug.

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Correct Modeling of Cisplatin: a Paradigmatic Case

Cited by 28 publications

References 22 publications

Structural Factors Affecting Binding of Platinum Anticancer Agents with Phospholipids: Influence of Charge and Phosphate Clamp Formation

Structural Factors Affecting Binding of Platinum Anticancer Agents with Phospholipids: Influence of Charge and Phosphate Clamp Formation

Accuracy Meets Interpretability for Computational Spectroscopy by Means of Hybrid and Double-Hybrid Functionals

Cisplatin interacting with buffering media and cysteine: Molecular insight due to Raman microspectroscopy

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