DFT/TDDFT investigation of the stepwise deprotonation in tetracycline: pKa assignment and UV–vis spectroscopy

Abstract

Tetracyclines are a class of derivatives of polycyclic naphthacene carboxamide, which have attracted wide interest in the pharmaceutical field for their use as antibiotics. These molecules are characterized by a substantial conformational flexibility and by the presence of different binding sites which endow tetracycline with a noticeable capability in binding biological targets. A salient property of tetracyclines is the presence of multiple acidic groups: four equilibrium constants have been measured for the fully protonated tetracycline (TCH 3 ? ) but so far no clear information concerning the pK a s of the various sites has been reported. We present here a computational investigation on the correlation between the acid-base and the spectroscopic properties of this important class of compounds. Starting from the TCH 3 ? species, the pK a of all the possible deprotonation sites has been computed by DFT calculations. The computed pK a s nicely compare with the experimental data, within 1 pK a unit, allowing us to individuate the products of the first deprotonation. This procedure has been iteratively repeated using as starting species the products singled out from the previous deprotonation, thus individuating the stepwise products of each deprotonation step. Then, the optical absorption spectra have been computed for all the species involved in the protonation/deprotonation equilibria, comparing the results with the experimental data. The good agreement between theory and experiment has allowed us to rationalize the correlation between the solution pH and the absorption spectra.

New Synthesis of Gold‐ and Silver‐Based Nano‐Tetracycline Composites

“…However, we assume that TC can interact with Ag ions at the amide position, owing to the affinity observed between Ag ions and the amide group . TC presents four acidic hydrogens, which can deprotonate in water, Ha, Hb, Hc, and Hd, with p K a values of 3.3, 7.3, 9.0, and 11.8 respectively (see Figure S1 in the Supporting Information) …”

Effect of micellar and sol–gel media on the spectral and kinetic properties of tetracycline and its complexes with Mg2+

“…TC in water can undergo several deprotonation equilibria, involving the functional groups bound to its linearly fused four-ring skeleton, whose dissociation constants have been broadly characterized ( pKa 1 = 3.5; pKa 2 = 7.3; pKa 3 = 9.5). 32,45,46 As a result, TC can exhibit in aqueous solution either a positive or a net negative charge according to the pH, the prevailing form being cationic, zwitterionic, monoanionic and di-anionic at pH 2, 5, 9, 11, respectively.…”

Facile Techniques to Synthesize Reduced Graphene Oxide for Removing Tetracycline From Water: Kinetics and Thermodynamics Studies

“…As a result, the adsorption of TC molecules on rGO was controlled by the stronger one. In pH > 7.7 solutions, TC was in the form of monovalent anion, + − −, or a divalent anion, 0 − − [15,41].…”