5-Fluorouracil (5FU), a common anti-cancer drug, occurs in four tautomeric forms and possesses two potential sites of both protonation and deprotonation. Tautomeric and resonance structures of the ionized forms of 5FU create the systems of connected equilibriums. Since there are contradictory reports on the ionized forms of 5FU in the literature, complex theoretical studies on neutral, protonated and deprotonated forms of 5FU, based on the broad spectrum of DFT methods, are presented. These indicate that the O4 oxygen is more willingly protonated than the O2 oxygen and the N1 nitrogen is more willingly deprotonated than the N3 nitrogen in a gas phase. Such preferences are due to advantageous charge delocalization of the respective ions, which is demonstrated by the NBO and ESP analyses. In an aqueous phase, stability differences between respective protonated and deprotonated forms of 5FU are significantly diminished due to the competition between the mesomeric effect and solvation. The calculated pKa values of the protonated, neutral and singly deprotonated 5FU indicate that 5FU does not exist in the protonated and double-deprotonated forms in the pH range of 0–14. The neutral form dominates below pH 8 and the N1 deprotonated form dominates above pH 8.
Pyridine, its N-oxide,
and their derivatives are exciting classes
of organic bases. These compounds show widespread biological activity,
and they are often used in synthesis. In this work results on theoretical
calculations of acid dissociation constants as pK
a of pyridine, its N-oxide, and their
derivatives were done based on the thermodynamic cycle in water and
acetonitrile. Additionally, gas-phase basicity (GB) and proton affinity
(PA) values were computed for systems studied. All pK
a values were obtained using B3LYP, M06-2X, and G4MP2
methods in the gas phase, which were combined with the PCM model calculations
(at the Hartree–Fock method) and with the use of four different
scale factors alpha. Theoretical GB, PA, and pK
a values were then compared with the available experimental
ones. Results obtained from B3LYP and M06-2X methods are quite similar
and compatible with experimental ones in terms of quality with correlation
coefficients values R
2 higher than 0.9,
whereas results received from G4MP2 deviate strongly. The calculated
pK
a values are highly sensitive to the
scale factors alpha used in the computational procedure. Root-mean-square
deviations (RMSD) between both theoretically and experimentally available
pK
a values of systems studied were also
computed. The RMSD values are lower than 0.8 for the best results,
suggesting that the theoretical model presented in this work is promising
for applications for pK
a calculations
of different classes of compounds.
SummaryDiosgenyl 2-amino-2-deoxy-β-D-glucopyranoside is a synthetic saponin exhibiting attractive pharmacological properties. Different pathways tested by us to obtain this glycoside are summarized here. Moreover, the synthesis of N-alkyl and N,N-dialkyl derivatives of the glucopyranoside is presented. Evaluation of antibacterial and antifungal activities of these derivatives indicates that they have no inhibitory activity against Gram-negative bacteria, whereas many of the tested N-alkyl saponins were found to inhibit the growth of Gram-positive bacteria and human pathogenic fungi.
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