Exploring the Influence of Spacers in EDTA-ß-Cyclodextrin Dendrimers: Physicochemical Properties and In Vitro Biological Behavior.

The synthesis of a new family of ethylenediaminetetraacetic acid (EDTA) core dimers and G0 dendrimers end-capped with two and four ß-cyclodextrin (ßCD) moieties was performed by click-chemistry conjugation, varying the spacers attached to the core. The structure analyses were achieved in DMSO-d6 and the self-inclusion process was studied in D2O by 1H-NMR spectroscopy for all platforms. It was demonstrated that the interaction with adamantane carboxylic acid (AdCOOH) results in a guest-induced shift of the self-inclusion effect, demonstrating the full host ability of the ßCD units in these new platforms without any influence of the spacer. The results of the quantitative size and water solubility measurements demonstrated the equivalence between the novel EDTA-ßCD platforms and the classical PAMAM-ßCD dendrimer. Finally, we determined the toxicity for all EDTA-ßCD platforms in four different cell lines: two human breast cancer cells (MCF-7 and MDA-MB-231), human cervical adenocarcinoma cancer cells (HeLa), and human lung adenocarcinoma cells (SK-LU-1). The new EDTA-ßCD carriers did not present any cytotoxicity in the tested cell lines, which showed that these new classes of platforms are promising candidates for drug delivery.

Zwitterion-neutral form equilibria and binding selectivity of pyridineboronic acids.

A 11B NMR study of 3-pyridineboronic acid at variable pH in water and 50 vol% aqueous dioxane confirms that the tautomeric equilibrium of the acid is shifted to the zwitterionic form in water, but to the molecular form in the mixed organic solvent. Interactions of 3- and 4-pyridineboronic acids with sialic acid, fructose and several other diols were studied by potentiometric titrations in a wide range of pH in water and water-organic mixtures. In all reaction media the stability of boronate complexes increases upon an increase in pH for neutral low acidic diols such as fructose and glucose but has the opposite trend for highly acidic sialic and lactic acids occurring as anionic species. The selectivity of pyridineboronic acids to sialate anions in an acidic medium is interpreted quantitatively by combining the pH-profiles with Brønsted type correlations for binding constants. In addition, mathematical expressions allowing one to predict the optimum pKa value of a boronic acid for the strongest binding of a given diol (sialic acid or fructose) at a given pH are suggested. The shifts in the tautomeric equilibrium induced by changing the solvent polarity in aqueous-organic mixtures are manifested in the magnitude of relative shifts of pKa of pyridineboronic acids induced by diol complexation.

Probing the Role of the Bridging Nitrogen in the Signaling Mechanism of an Anthracene-Boronic Acid Sugar Sensor and a Different Version of the PET-Based Mechanism.

The N-quaternized derivative 5 of the James-Shinkai anthracene-boronic acid fluorescence sugar sensor 1 was prepared to probe the role of the bridging nitrogen in the signaling mechanism of 1. Both 5 and 1 contain positively charged bridging groups NMe+ or NH+, respectively, but 5 lacks the ability to form the intramolecular ammonium-boronate doubly ionic hydrogen bond present in 1. Receptors 1 and 5 display opposite fluorescence vs pH profiles with a small turn-on effect of the sugar binding to the zwitterion of 5 in contrast to a large effect observed with 1. It is concluded that the ammonium-boronate hydrogen bond is essential for the signaling mechanism of 1. Its possible function is enabling the PET quenching effect by shifting the NH+ proton toward boronate anion inside the hydrogen bond, the degree of which is modulated by the ester formation with diols affecting the basicity of boronate anion. This mechanism agrees with observed signaling selectivity of 1 toward a series of di- and polyols of variable structures as well as with the behavior of 1 in buffered D2O and methanol solvents at controlled pH and provides an addition to the established "loose bolt" mechanism signaling mode essential for receptors with nonpolar fluorophores.

Fluorescence Sensing of Monosaccharides by Bis-boronic Acids Derived from Quinolinium Dicarboxamides: Structural and Spectroscopic Studies.

Three new diboronic acid-substituted bisquinolinium salts were synthesized, structurally described by single-crystal X-ray diffraction, and studied in-depth as fluorescent receptors for six monosaccharides and two open-chain polyols in water at physiological pH. The dicationic pyridine-2,6-dicarboxamide-based receptors contain two N-quinolinium rings as the fluorescent units covalently linked to three different isomers of phenylboronic acid (ortho, 2; meta, 3; and para, 4) as chelating binding sites for polyols. Additions of glucose/fructose in the micromolar concentration range to receptors 2 and 3 induce significant fluorescence changes, but in the presence of arabinose, galactose, mannose, and xylose, only modest optical changes are observed. This optical change is attributed to a static photoinduced electron transfer mechanism. The meta-diboronic receptor 3 exhibited a high affinity/selectivity toward glucose (K = 3800 M-1) over other monosaccharides including common interfering species such as fructose and mannitol. Based on multiple spectroscopic tools, electrospray ionization high-resolution mass spectrometry, crystal structures, and density functional theory calculations, the binding mode between 3 and glucose is proposed as a 1:1 complex with the glucofuranose form involving a cooperative chelating diboronate binding. These results demonstrate the usefulness of a new set of cationic fluorescent diboronic acid receptors with a strong ability for optical recognition of glucose in the sub-millimolar concentration range.

Anion Recognition by Benzoxaborole.

The binding types (H-bonding or coordinate) and stability constants for complexes of 11 mono- and di-anions with benzoxaborole (1) were determined by 1H and 11B NMR titrations in DMSO or MeCN. Compared to phenylboronic acid (PBA), 1 is a stronger Lewis acid and a poorer H-bond donor with only one B-OH group, which is expected therefore to recognize anions mostly through the coordinate bonding. This is the case however only with F-, HPO42-, and PhPO32- anions, which are coordinately bonded to 1, and partially with SO42-, which forms only the H-bonded complex with PBA, but both H-bonded and coordinate complexes with 1. The majority of tested anions (AcO-, PhPO3H-, (PhO)2PO2-, Cl-, and Br-) form H-bonded complexes with both 1 and PBA, whereas H2PO4- changes the binding mode from coordinate for PBA to H-bonded for 1. The preferable binding type for each anion is confirmed by calculations of DFT-optimized structures of the anion complexes of 1. The preferable binding type can be rationalized considering the effects of the steric hindrance, more significant for the coordinate bonding, and of increased anion basicity, which is favorable for both binding types, but enhances the strength of coordinate bonding more significantly than the strength of H-bonding.

Boronic acid complexes with amino phenolic N,O-ligands and their use for non-covalent protein fluorescence labeling.

Phenylboronic acid (PBA) forms neutral tetrahedral N,O-coordinated 6-membered cyclic complexes with stability constants reaching the values as large as 1.3 × 104 M-1 at pH 7.4 in water with amino phenolic compounds including 2-(2'-hydroxyphenyl)-1H-benzimidazole (HPBI) often used for protein probing and labeling. The crystal structures of isolated complexes demonstrate unusually high for boronate adducts degree of the tetrahedral character of the boron atom with short B-N bonds in agreement with their high solution stability. The complexation of PBA with HPBI, causes a strong enhancement of the fluorescence of the "enol" form of the ligand, increases the affinity of the dye to a protein (bovine serum albumin) and makes more pronounced the shift in emission maximum induced by the protein binding. Similar, but larger effects are observed with an amino HPBI derivative and with a stronger boronic acid benzoxaborole. Thus, the binding constant to the protein about 2 × 104 M-1 for free HPBI increases to 1.2 × 106 M-1 for the complex of 5-amino-HPBI with benzoxaborole making it suitable for an efficient non-covalent protein labeling or bioconjugation.

Examination of pinanediol-boronic acid ester formation in aqueous media: relevance to the relative stability of trigonal and tetrahedral boronate esters.

The interaction of pinanediol with 2-fluorophenylboronic acid and several other substituted phenylboronic acids was studied in 40% vol. aqueous acetonitrile by 1H and 11B NMR, potentiometric and spectrophotometric titrations at variable pH values. The experimental results reveal the formation of a very stable trigonal ester (Ktrig ≈ 2 × 104 M-1) and a significantly less stable tetrahedral hydroxocomplex (Ktet ≈ 5 × 103 M-1) in contrast to the traditionally observed inverted order of stabilities Ktrig < Ktet. Comparison of the crystal structure of the trigonal ester isolated from aqueous acetonitrile with the DFT simulated structure of the respective hydroxocomplex shows that an unusual order of stabilities Ktrig > Ktet is observed in spite of the existence of the usual strain release effect in the O-B-O angle considered responsible for the typically observed increased stability of the tetrahedral hydroxocomplex. A complementary study of the stability of the six-membered cyclic boronate esters of chromotropic acid demonstrated the order Ktrig ≪ Ktet although the strain was absent in these esters. The results for m-, p-substituted phenylboronic acids show that the stability of both five- and six-membered trigonal esters formed with pinanediol and chromotropic acid, respectively, is insensitive to electronic effects but the electron accepting substituents stabilize the hydroxocomplexes. It follows from the whole set of results that Ktet can be much larger than Ktrig in the absence of the strain, but with a sufficiently acidic diol, and that the presence of the strain does not necessarily make Ktet larger than Ktrig for a less acidic diol with a purely saturated hydrocarbon backbone. Thus, the electronic effects manifested in the acidity of the diol appear to be more significant than the strain release effect in determining the Ktet/Ktrig ratio.

Mechanistic study of carboxylic acid and phosphate ester cleavage by oximate metal complexes surpassing the limiting reactivity of highly basic free oximate anions.

Two tridentate and one tetradentate new ligands containing the terminal oxime group separated from secondary amino and pyridine groups as additional binding sites by two or three methylene groups have been prepared. Their acid-base properties, as well as the composition and stability of their complexes with Zn(ii) and Cd(ii) ions, were determined by potentiometric and spectrophotometric titrations. The X-ray structure of a Cd(ii) complex of a related tridentate oxime ligand previously studied in solution was determined. All oximate complexes show high reactivity in the cleavage of aryl acetates, paraoxon, parathion and 4-nitrophenyl diphenyl phosphate, with rate constants significantly surpassing the limiting rate constants observed for highly basic free oximate anions. The second-order rate constants for individual oximate complexes in solution are assigned to each ligand, metal cation and substrate. The results of the cleavage of 4-substituted phenyl acetates were analyzed in terms of Brønsted correlations with the leaving group pKa, which demonstrated a change in the rate determining step from the nucleophilic attack to the leaving group departure upon an increase in the leaving group basicity. The zero slope of the Brønsted correlation for the nucleophilic attack indicates transition state stabilization through electrophilic assistance by the metal ion. This interpretation is supported by metal selectivity in the relative efficiency of the cleavage of paraoxon and parathion. The existence of the alpha-effect in ester cleavage by coordinated oximates is confirmed by an analysis of the Brønsted correlations with the nucleophile basicity for metal bound oximate and alkoxo or hydroxo nucleophiles. The very high reactivity of the oximate complexes of the new ligands is attributed to transition state stabilization and to the removal of the solvational imbalance of oximate anions that impedes the expected increase in the reactivity of highly basic free anions.

Recent Advances in Application of Azobenzenes Grafted on Mesoporous Silica Nanoparticles in Controlled Drug Delivery Systems Using Light as External Stimulus.

Hybrid materials based on Mesoporous Silica Nanoparticles (MSN) have attracted plentiful attention due to the versatility of their chemistry, and the field of Drug Delivery Systems (DDS) is not an exception. MSN present desirable biocompatibility, high surface area values, and a well-studied surface reactivity for tailoring a vast diversity of chemical moieties. Particularly important for DDS applications is the use of external stimuli for drug release. In this context, light is an exceptional alternative due to its high degree of spatiotemporal precision and non-invasive character, and a large number of promising DDS based on photoswitchable properties of azobenzenes have been recently reported. This review covers the recent advances in design of DDS using light as an external stimulus mostly based on literature published within last years with an emphasis on usually overlooked underlying chemistry, photophysical properties, and supramolecular complexation of azobenzenes.

Spectrophotometric, fluorimetric and electrochemical selective pyrophosphate/ATP sensing based on the dimethyltin(IV)-tiron system.

Sensing of pyrophosphate anion (PPi) in the presence of nucleotide triphosphates allows the real time monitoring of the polymerase chain reaction. To get a deeper understanding of the factors involved in PPi/nucleotide triphosphate discrimination, a detailed study on the performance of a dimethyltin (IV)-catecholate complex capable of both separate fluorimetric or electrochemical detection of PPi in the presence of adenosine triphosphate (ATP) has been undertaken. Dimethyltin (IV) tightly binds PPi or ATP, and forms a stable 1:1 complex with tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid) in water. The complexation equilibria with all components are characterized quantitatively by potentiometric and spectroscopic titrations. Pyrophosphate anion can be detected owing to its ability to release free tiron from the complex by measuring either a fluorimetric or an electrochemical signal. On the contrary, ATP does not displace tiron but causes an interference with PPi in the fluorimetric detection method due to the formation of a ternary Me2Sn(IV)-tiron-ATP complex with optical properties intermediate between those of free and bound tiron. In the electrochemical (square wave voltammetry) method, the ternary ATP complex shows a separate peak which does not coincide with the peaks of neither free nor bound tiron, thus making possible the simultaneous detection of ATP in addition to PPi.

Stability of doubly and triply H-bonded complexes governed by acidity-basicity relationships.

We used our recently proposed acidity-basicity interplay (ABI) model (Chem. Sci., 2018, 9, 4402) and the Jorgensen secondary interactions hypothesis (JSIH) to rationalise the experimentally observed trends in the formation constants of doubly and triply H-bonded systems with -NHO[double bond, length as m-dash]C- and -NHN- interactions. Unlike the JSIH, the ABI interpretation can explain the trends in the complexation of amide/imide homo- and heterodimers as well as ADA-DAD clusters. We found that the strongest H-bonds play a very important role, a condition which offers an alternative to the well established JSIH to modulate the stability of these relevant systems.

Substrate Specificity and Leaving Group Effect in Ester Cleavage by Metal Complexes of an Oximate Nucleophile.

Deprotonated zinc(II) and cadmium(II) complexes of a tridentate oxime nucleophile (1, OxH) show a very high reactivity, breaking by 2-3 orders of magnitude the previously established limiting reactivity of oximate nucleophiles in the cleavage of substituted phenyl acetates and phosphate triesters, but are unreactive with p-nitrophenyl phosphate di- and monoesters. With reactive substrates, these complexes operate as true catalysts through an acylation-deacylation mechanism. Detailed speciation and kinetic studies in a wide pH interval allowed us to establish as catalytically active forms [Cd(Ox)]+, [Zn(Ox)(OH)], and [Zn(Ox)(OH)2]- complexes. The formation of an unusual and most reactive zinc(II) oximatodihydroxo complex was confirmed by electrospray ionization mass spectrometry data and supported by density functional theory calculations, which also supported the previously noticed fact that the coordinated water in [Zn(OxH)(H2O)2]2+ deprotonates before the oxime. Analysis of the leaving group effect on the cleavage of phenyl acetates shows that the rate-determining step in the reaction with the free oximate anion is the nucleophilic attack, while with both zinc(II) and cadmium(II) oximate complexes, it changes to the expulsion of the leaving phenolate anion. The major new features of these complexes are (1) a very high esterolytic activity surpassing that of enzyme hydrolysis of aryl acetate esters and (2) an increased reactivity of coordinated oxime compared to free oxime in phosphate triester cleavage, contrary to the previously observed inhibitory effect of oxime coordination with these substrates.

Brønsted versus Lewis Acid Type Anion Recognition by Arylboronic Acids.

Interactions between arylboronic acids and a series of anions as tetrabutylammonium salts in DMSO and MeCN were studied by (1)H and (11)B NMR as well as spectrophotometrically. Boronic acids act as Brønsted acid type receptors through hydrogen bonding with B(OH)2 hydroxyl groups toward Cl(-), Br(-), HSO4(-), and AcO(-), but they act as Lewis acid type receptors toward F(-) and H2PO4(-), which form tetrahedral adducts with the B(III) center of boronic acids, although there is also evidence for some contribution of hydrogen bonding with these anions. The Hammett plot for the binding constants of AcO(-) with 3- and 4-substituted phenylboronic acids in DMSO is nonlinear, with a small negative slope for electron-donating and weakly electron-accepting substituents and a large positive slope for strongly electron-accepting substituents. 3-Nitrophenylboronic acid recognizes zwitterions of amino acids in DMSO, and its UV absorption maximum undergoes a significant red shift in the presence of acetate anions, providing a means for sensing anions optically. Arylboronic acids as Brønsted acid type receptors show relatively low sensitivity to solvent polarity and are equally or even more efficient than widely employed proton donors such as ureas or dicarboxamides.

Reagentless polyol detection by conductivity increase in the course of self-doping of boronate-substituted polyaniline.

We report on the novel reagentless and label-free detection principle based on electroactive (conducting) polymers considering sensors for polyols, particularly, saccharides and hydroxy acids. Unlike the majority of impedimetric and conductometric (bio)sensors, which specific and unspecific signals are directed in the same way (resistance increase), making doubtful their real applications, the response of the reported system results in resistance decrease, which is directed oppositely to the background. The mechanism of the resistance decrease is the polyaniline self-doping, i.e., as an alternative to proton doping, an appearance of the negatively charged aromatic ring substituents in polymer chain. Negative charge "freezing" at the boron atom is indeed a result of complex formation with di- and polyols, specific binding. Changes in Raman spectra of boronate-substituted polyaniline after addition of glucose are similar to those caused by proton doping of the polymer. Thermodynamic data on interaction of the electropolymerized 3-aminophenylboronic acid with saccharides and hydroxy acids also confirm that the observed resistance decrease is due to polymer interaction with polyols. The first reported conductivity increase as a specific signal opens new horizons for reagentless affinity sensors, allowing the discrimination of specific affinity bindings from nonspecific interactions.

Oximate metal complexes breaking the limiting esterolytic reactivity of oximate anions.

Zinc(II) and cadmium(II) complexes of a tridentate oximate ligand cleave 4-nitrophenyl acetate with rate constants surpassing by two orders of magnitude those reported as the maximum possible level for highly basic free oximate anions as a result of removal of the "solvational imbalance" of the nucleophile by metal coordination.

Substituent effects and pH profiles for stability constants of arylboronic acid diol esters.

Stability constants of boronic acid diol esters in aqueous solution have been determined potentiometrically for a series of meta-, para-substituted phenylboronic acids and diols of variable acidity. The constants ß(11-1) for reactions between neutral forms of reactants producing the anionic ester plus proton follow the Hammett equation with ρ depending on pKa of diol and varying from 2.0 for glucose to 1.29 for 4-nitrocatechol. Observed stability constants (K(obs)) measured by UV-vis and fluorometric titrations at variable pH for esters of 4,5-dihydroxy-1,3-benzenedisulfonate (Tiron) generally agree with those expected on the basis of ß(11-1) values, but the direct fitting of K(obs) vs pH profiles gives shifted pKa values both for boronic acids and diol as a result of significant interdependence of fitting parameters. The subsituent effects on absorption and fluorescence spectra of Tiron arylboronate esters are characterized. The K(obs) for Tiron determined by (11)B NMR titrations are approximately 1 order of magnitude smaller than those determined by UV-vis titrations under identical conditions. A general equation, which makes possible an estimate of ß(11-1) for any pair of boronic acid and diol from their pKa values, is proposed on the basis of established Brönsted-type correlation of Hammett parameters for ß(11-1) with acidity of diols. The equation allows one to calculate stability constants expected only on basis of acid-base properties of the components, thus permitting more strict evaluation of contributions of additional factors such as steric or charge effects to the ester stability.

Supramolecular complexations of natural products.

Complexations of natural products with synthetic receptors as well as the use of natural products as host compounds are reviewed, with an emphasis on possible practical uses or on biomedical significance. Applications such as separation, sensing, enzyme monitoring, and protection of natural drugs are first outlined. We then discuss examples of complexes with all important classes of natural compounds, such as amino acids, peptides, nucleosides/nucleotides, carbohydrates, catecholamines, flavonoids, terpenoids/steroids, alkaloids, antibiotics and toxins.

Selective fluorometric detection of pyrophosphate by 3-hydroxyflavone-diphenyltin(IV) complex in aqueous micellar medium.

3-Hydroxyflavonate-diphenyltin(IV) chloride (Ph(2)Sn(Ofl)Cl) was prepared and characterized structurally by single crystal X-ray diffraction. The compound possesses high fluorescence (λ(max) 464 nm with excitation at 400 nm) in neutral aqueous solutions containing 5 mM cetyltrimethylammonium chloride and does not lose the flavonol ligand even at high dilution. The fluorescence is selectively quenched by pyrophosphate (PPi) (linear range 0-5 µM, detection limit 0.1 µM). Determination of 1 µM PPi tolerates the presence of 100-fold excess of AMP, ADP, inorganic phosphate and acetate, and 10-fold excess of ATP. From concentration profiles of the quenching effect it is concluded that quenching occurs due to formation of the complex (Ph(2)Sn(Ofl))(3)PPi, which is transformed at higher PPi concentrations to a simple 1 : 1 complex Ph(2)Sn(Ofl)(PPi). No flavonol ligand exchange with PPi is observed. A series of related organotin(IV) complexes were prepared in situ by reacting 3-hydroxyflavone with Me(2)SnCl(2), PhSnCl(3) and n-BuSnCl(3). The derivatives of Me(2)SnCl(2) and PhSnCl(3) behave similarly to Ph(2)Sn(Ofl)Cl but with lower sensitivity to PPi. However, the n-butyltin(IV) derivative tentatively of the composition n-BuSn(Ofl)(2) undergoes fluorescence enhancement rather than quenching in the presence of PPi in the µM concentration range. The results of this study demonstrate that the use of metal flavonol complexes as optical sensors for anions is a promising approach.

Electrophilic assistance to the cleavage of an RNA model phopshodiester via specific and general base-catalyzed mechanisms.

Kinetics of transesterification of the RNA model substrate 2-hydroxypropyl 4-nitrophenyl phosphate promoted by Mg(2+) and Ca(2+), the most common biological metals acting as cofactors for nuclease enzymes and ribozymes, as well as by Co(NH(3))(6)(3+), Co(en)(3)(3+), Li(+), and Na(+) cations, often employed as mechanistic probes, was studied in 80% v/v (50 mol %) aqueous DMSO, a medium that allows one to discriminate easily specific base (OH(-)-catalyzed) and general base (buffer-catalyzed) reaction paths. All cations assist the specific base reaction, but only Mg(2+) and Na(+) assist the general base reaction. For Mg(2+)-assisted reactions, the solvent deuterium isotope effects are 1.23 and 0.25 for general base and specific base mechanisms, respectively. Rate constants for Mg(2+)-assisted general base reactions measured with different bases fit the Brønsted correlation with a slope of 0.38, significantly lower than the slope for the unassisted general base reaction (0.77). Transition state binding constants for catalysts in the specific base reaction (K(‡)(OH)) both in aqueous DMSO and pure water correlate with their binding constants to 4-nitrophenyl phosphate dianion (K(NPP)) used as a minimalist transition state model. It was found that K(‡)(OH) ≈ K(NPP) for "protic" catalysts (Co(NH(3))(6)(3+), Co(en)(3)(3+), guanidinium), but K(‡)(OH) ≫ K(NPP) for Mg(2+) and Ca(2+) acting as Lewis acids. It appears from results of this study that Mg(2+) is unique in its ability to assist efficiently the general base-catalyzed transesterification often occurring in active sites of nuclease enzymes and ribozymes.

Schiff base formation and recognition of amino sugars, aminoglycosides and biological polyamines by 2-formyl phenylboronic acid in aqueous solution.

Interactions of 2-, 3- and 4-formyl phenylboronic acids (FPBAs) with sugars, amino sugars, aminoglycosides and various poly- and monoamines have been studied by UV-vis, (1)H and (11)B NMR titrations in water at variable pH. Behavior of 2-FPBA was anomalous in several aspects. Transformation of the acid into its conjugate base was slow in NMR time scale and was accompanied by intramolecular cyclization affording the respective benzoboroxole. The equilibrium constants for imine formation (K(imine)) between 2-FPBA and simple monoamines including amino sugars were ca. 2 orders of magnitude larger than those with other isomers. Still one order of magnitude larger K(imine) values were observed for 2-FPBA with aminoglycosides (kanamycin, amikacin, gentamicin, neomycin) and polyamines (spermine, spermidine). The examination of UV-vis and (11)B NMR spectra of imines formed with 2-FPBA showed that formally neutral Schiff bases in fact were zwitterionic species containing a protonated imine group and an anionic B(OH)(3)(-) group. The enhanced stability of imines with monoamines can therefore be attributed to the electrostatic stabilization provided by the zwitterionic structure and further increased stability of imines with antibiotics and polyamines is explicable by additional stabilization of the borate anionic group by ion paring with ammonium groups not involved in Schiff base formation. Thanks to high molar absorptivity of protonated imines interaction of 2-FPBA with aminoglycosides allows detecting them spectrophotometrically in a µM concentration range in neutral aqueous solutions in the presence of sugars, amino sugars and amino acids.