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The aim of this investigation is to identify, by in silico and in vitro methods, the molecular determinants, e.g., solubility in an aqueous medium and lipophilic properties, which have an effect on the bioavailability of five selected fluoroquinolones. These properties were estimated by analysis of the electrostatic potential pattern and values of free energy of solvation as well as the partition coefficients of the studied compounds. The study is based on theoretical quantum-chemical methods and a simple experimental shake-flask technique with two immiscible phases, n-octanol and phosphate buffer. The solvation free energy values of compounds in both environments appeared to be negative. The wide range of electrostatic potential from negative to positive demonstrates the presence of dipole–dipole intermolecular interactions, while the high electron density at various sites indicates the possibility of hydrogen bond formation with solvent molecules. High partition coefficient values, obtained by summing the atomic contributions, did not take various correction factors into account and therefore were not accurate. Theoretical partition coefficient values based on more accurate algorithms, which included these correction factors (fragmental methods), yielded more accurate values. Theoretical methods are useful tools for predicting the bioavailability of fluoroquinolones.

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“…It is worth mentioning that atomic-contribution methods do not take correction factors into account [16, 20–23]. …”

Section: Methodsmentioning

confidence: 99%

Experimental and theoretical studies on the molecular properties of ciprofloxacin, norfloxacin, pefloxacin, sparfloxacin, and gatifloxacin in determining bioavailability

et al. 2014

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“…In addition to fragmental constants, ACD/LOGP [18] uses atom contribution methods in order to estimate missing fragmental increments. ACD/LOGP uses rules similar to those for CLOGP in order to calculate correlation factors.…”

Section: Log P Calculation Programsmentioning

confidence: 99%

Comparison of Predictivities of Log P Calculation Models Based on Experimental Data for 134 Simple Organic Compounds

Sakuratani¹,

Kasai²,

Noguchi³

et al. 2007

QSAR Comb. Sci.

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Predictivities of six log P calculation models (CLOGP, KOWWIN, ACD/LOGP, SLOGP, VLOGP and COSMO thermo) are compared using a common experimental dataset, which does not contain any of the compounds used in the training set for the six models. The former three models, which are based on fragment methods, showed better accuracy (r ¼ 0.87 -0.91) than SLOGP, which is based on the atom contribution method and VLOGP and COSMO thermo, which are property-based models. The trends of prediction by each model are described based on chemical structure and molecular weight. For all six models, several compounds had a significantly greater calculated log P value than the experimental log P value. It is interesting to note that most of these compounds had ionic moieties.

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“…However, already in 1964 octanolwater partition coefficients were implemented as standard in QSAR analysis because of the similarity of noctanol and lipophilic biophases [7]. QSPR with focus on octanol-water log P were integral parts of the foundation of log P calculation software as Rekker's fragment additivity method [11,12], CLOGP (for review, see [10]), ACDLabs [13], several atomistic approaches and the recent surface-integral model using local properties from semiempirical MO-calculations and their integrals over the molecular surface [14]. Based on large log P databases -in 1995, Hansch, Leo and Hoekman documented ca.…”

Section: Introductionmentioning

confidence: 99%