Overview of experimental and computational methods for the determination of the pKa values of 5-fluorouracil, cyclophosphamide, ifosfamide, imatinib and methotrexate

Mioduszewska, Katarzyna; Dołżonek, Joanna; Wyrzykowski, Dariusz; Kubik, Łukasz; Wiczling, Paweł; Sikorska, Celina; Toński, Michał; Kaczyński, Zbigniew; Stepnowski, Piotr; Białk‐Bielińska, Anna

doi:10.1016/j.trac.2017.09.009

Cited by 62 publications

(34 citation statements)

References 48 publications

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“…The selected compounds have differences in their acidic/basic METHX is an antitumor drug with two acidic groups (pK a1 ¼ 3.4 and pK a2 ¼ 4.7) and one basic group (pK a3 ¼ 5.7). 66 At pH 3, this compound possesses partial negative and full positive charges (zwitterionic), which correspond to the dissociation of a-carboxyl group (pK a1 ¼ 3.4) and N(1) of the pteridine ring (pK a3 ¼ 5.7). As shown in Fig.…”

Section: Selectivity Of G-mno 2 /Cs/pge For Negatively Charged Compoundsmentioning

confidence: 99%

Fabrication of novel electrochemical sensors based on modification with different polymorphs of MnO₂nanoparticles. Application to furosemide analysis in pharmaceutical and urine samples

2018

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Section: Selectivity Of G-mno 2 /Cs/pge For Negatively Charged Compoundsmentioning

confidence: 99%

Fabrication of novel electrochemical sensors based on modification with different polymorphs of MnO₂nanoparticles. Application to furosemide analysis in pharmaceutical and urine samples

2018

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“…In other words, the PCA approach was adopted for grouping the studied PAHs based on their structural similarity. Since the usefulness of this technique for describing the properties of different chemicals was earlier confirmed (Sikorska and Puzyn 2015 ; Mioduszewska et al 2017 ), and given the enormity of advantages resulting from the application of this type of approach (such as speed, low cost, and safety), this approach was performed in the present contribution. In particular, we have presented the structures of PAHs in the space of the first and second principle components (score plot), in accordance with the demonstrative criterion (Abdi and Williams 2010 ).…”

Section: Methodsmentioning

confidence: 99%

Helical Multi-walled Carbon Nanotubes as an Efficient Material for the Dispersive Solid-Phase Extraction of Low and High Molecular Weight Polycyclic Aromatic Hydrocarbons from Water Samples: Theoretical Study

Paszkiewicz

Sikorska

Leszczyńska

et al. 2018

Water Air Soil Pollut

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The differences in effectiveness of multi-walled carbon nanotubes (MWCNTs) as the dispersive solid-phase extraction (dSPE) sorbent for the selective extraction of polycyclic aromatic hydrocarbons (PAHs) were explained on the basis of theoretical study. It was observed that for low molecular weight PAHs, the recoveries using non-helical and helical MWCNTs were similar. In contrary, for PAHs containing five or more aromatic rings, the extraction efficiency was higher using HMWCNTs than for non-helical ones. Principle component analysis (PCA) as well as providing structural parameters and interaction energies for adsorption processes (PAH + CNT → PAH-CNT) have been used for this purpose. All the PAH + CNT → PAH-CNT adsorption processes considered were found to be thermodynamically favorable. However, the adsorption energies (Eads) for PAHs and the helical carbon nanotube surface estimated for the B(a)P-HCNT and I(1,2,3-cd)P-HCNT are substantially less negative than those observed for PAH molecules interacting with the non-helical CNT. Namely, the Eads calculated in simulated aqueous environment for the B(a)P-MWCNT(6,2) and I(1,2,3-cd)P-MWCNT(6,2) were respectively − 43.32 and − 59.98 kcal/mol, while values of only − 7.75 kcal/mol (B(a)P-HCNT) and − 9.13 kcal/mol (I(1,2,3-cd)P-HCNT) were found for the corresponding PAH-HCNT systems. Therefore, we conclude that the replacement of MWCNTs with HCNTs leads to PAH-HCNT systems in which the interaction energies are much smaller than those estimated for the corresponding PAH-MWCNT systems. HMWCNTs are therefore recommended as the dSPE sorbent phase for the extraction of both low and high molecular weight PAHs from water samples.Electronic supplementary materialThe online version of this article (10.1007/s11270-018-3884-0) contains supplementary material, which is available to authorized users.

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“…The effects of 5-FU substitution on DNA and RNA stability are a net result of multiple forces that are differentially affected by the strong electronegativity of 5-FU. The pK A for the imino hydrogen of 5-FU is in the physiological range [ 85 , 86 ]. Thus, 5-FU base pairs are anticipated to be more dynamic and potentially contribute less to nucleic acid stability than native base pairs.…”

Section: Synthesis Of 5-fu Substituted Rna and Dna For Biophysicalmentioning

confidence: 99%

Chemistry of Fluorinated Pyrimidines in the Era of Personalized Medicine

Gmeiner

2020

Molecules

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We review developments in fluorine chemistry contributing to the more precise use of fluorinated pyrimidines (FPs) to treat cancer. 5-Fluorouracil (5-FU) is the most widely used FP and is used to treat > 2 million cancer patients each year. We review methods for 5-FU synthesis, including the incorporation of radioactive and stable isotopes to study 5-FU metabolism and biodistribution. We also review methods for preparing RNA and DNA substituted with FPs for biophysical and mechanistic studies. New insights into how FPs perturb nucleic acid structure and dynamics has resulted from both computational and experimental studies, and we summarize recent results. Beyond the well-established role for inhibiting thymidylate synthase (TS) by the 5-FU metabolite 5-fluoro-2′-deoxyuridine-5′-O-monophosphate (FdUMP), recent studies have implicated new roles for RNA modifying enzymes that are inhibited by 5-FU substitution including tRNA methyltransferase 2 homolog A (TRMT2A) and pseudouridylate synthase in 5-FU cytotoxicity. Furthermore, enzymes not previously implicated in FP activity, including DNA topoisomerase 1 (Top1), were established as mediating FP anti-tumor activity. We review recent literature summarizing the mechanisms by which 5-FU inhibits RNA- and DNA-modifying enzymes and describe the use of polymeric FPs that may enable the more precise use of FPs for cancer treatment in the era of personalized medicine.

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Overview of experimental and computational methods for the determination of the pKa values of 5-fluorouracil, cyclophosphamide, ifosfamide, imatinib and methotrexate

Cited by 62 publications

References 48 publications

Fabrication of novel electrochemical sensors based on modification with different polymorphs of MnO₂nanoparticles. Application to furosemide analysis in pharmaceutical and urine samples

Fabrication of novel electrochemical sensors based on modification with different polymorphs of MnO₂nanoparticles. Application to furosemide analysis in pharmaceutical and urine samples

Helical Multi-walled Carbon Nanotubes as an Efficient Material for the Dispersive Solid-Phase Extraction of Low and High Molecular Weight Polycyclic Aromatic Hydrocarbons from Water Samples: Theoretical Study

Chemistry of Fluorinated Pyrimidines in the Era of Personalized Medicine

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Overview of experimental and computational methods for the determination of the pKa values of 5-fluorouracil, cyclophosphamide, ifosfamide, imatinib and methotrexate

Cited by 62 publications

References 48 publications

Fabrication of novel electrochemical sensors based on modification with different polymorphs of MnO2nanoparticles. Application to furosemide analysis in pharmaceutical and urine samples

Fabrication of novel electrochemical sensors based on modification with different polymorphs of MnO2nanoparticles. Application to furosemide analysis in pharmaceutical and urine samples

Helical Multi-walled Carbon Nanotubes as an Efficient Material for the Dispersive Solid-Phase Extraction of Low and High Molecular Weight Polycyclic Aromatic Hydrocarbons from Water Samples: Theoretical Study

Chemistry of Fluorinated Pyrimidines in the Era of Personalized Medicine

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Fabrication of novel electrochemical sensors based on modification with different polymorphs of MnO₂nanoparticles. Application to furosemide analysis in pharmaceutical and urine samples

Fabrication of novel electrochemical sensors based on modification with different polymorphs of MnO₂nanoparticles. Application to furosemide analysis in pharmaceutical and urine samples