Real-time monitoring of nanomolar binding to a cyclodextrin monolayer immobilized on a Si/SiO2/novolac surface using white light reflectance spectroscopy: the case of triclosan.

The monitoring of the antibacterial agent triclosan binding at nanomolar concentration from an aqueous solution by employing a well-packed monolayer with a predetermined single orientation made of specifically synthesized 2,3-dimethyl-6-(undec-10-enamide)-6-deoxy-ß-cyclodextrin (DMBUA) on a silicon wafer (Si/SiO(2)) coated with a novolac resin is reported. A white light reflectance spectroscopy (WLRS) setup was used for the real-time monitoring of the DMBUA deposition and triclosan binding processes. Film thicknesses obtained by WLRS were in very good agreement with the ones measured by X-ray reflectivity (XRR) experiments. Triclosan binds strongly to the DMBUA monolayer (logK(assoc)=6.68). NMR studies in aqueous solution indicated that the chlorophenolyl ring rather than the dichlorophenyl ring is preferentially inserted into DMBUA cups. The current detecting system that requires no tedious surface chemistry, no thiolated cyclodextrins, no gold surfaces, and no expensive equipment may be useful in capturing small molecules and may permit various applications, e.g., preparation of antimicrobial surfaces.

Novel polycarboxylated EDTA-type cyclodextrins as ligands for lanthanide binding: study of their luminescence, relaxivity properties of Gd(iii) complexes, and PM3 theoretical calculations.

Novel -type cyclodextrin (CD) derivatives, , and , bearing 6, 7 and 8 bis(carboxymethyl)amino (iminodiacetic acid) groups, respectively, were prepared, and their complexation with Eu(iii), Tb(iii) and Gd(iii) ions was studied. Luminescence titrations and mass spectrometry showed formation of multimetal complexes ( 2 to 3, mainly 3 and exactly 4 metal ions), whereas luminescence lifetime measurements revealed the presence of exchangeable water molecules. Semiempirical quantum mechanical calculations, performed by the PM3 method and assessed by DFT calculations on model ligands, indicated efficient multi-metal complexation, in agreement with the experiment. The structures showed coordination of the metal ions in the outer primary side of the CDs via 4 carboxylate O atoms, 2 N atoms and a glucopyranose O atom per metal ion. Coordination of water molecules was also predicted, in accordance with experimental results. Calculated bond lengths and angles were in agreement with literature experimental values of lanthanide complexes. Calculated energies showed that complex stability decreases in the order > > . (1)H NMR molecular relaxivity measurements for the Gd(iii) complexes of , or in water afforded values 4 to 10 times higher than the relaxivity of a commercial contrast agent at 12 MHz, and 6 to 20 times higher at 100 MHz. Solutions of and Gd(iii) complexes in human blood plasma displayed relaxivity values at 100 MHz 7 and 12 times, respectively, higher than the commercial agent. MTT tests of the Gd(iii) complexes using human skin fibroblasts did not show toxicity. Attempts to supramolecularly sensitize the luminescence of the lanthanide complexes using various aromatic CD guests were ineffective, evidently due to large guest-metal distances and inefficient inclusion. The described lanthanide complexes, could be useful as contrast agents in MRI.

Crystal structure of the inclusion complex of the antibacterial agent triclosan with cyclomaltoheptaose and NMR study of its molecular encapsulation in positively and negatively charged cyclomaltoheptaose derivatives.

The inclusion complexes of triclosan with native cyclomaltoheptaose (beta-cyclodextrin, betaCD) as well as with negatively and positively charged derivatives are studied. The structure of the inclusion complex betaCD/triclosan in the crystalline state [P1, a=15.189(5), b=15.230(6), c=16.293(6), alpha=91.07(4), beta=91.05(3) gamma=100.71(3)] comprises two crystallographically independent host macrocycles A and B. The packing results in betaCD dimers that align head-to-head and form infinite channels along the c-axis. Only one guest molecule statistically disordered over two positions, (the dichlorophenyl ring in the cavities of either A or B) corresponds to each dimer (a 2:1 host/guest complex). The enclosed dichlorophenyl ring enters the dimer through the primary side, whereas the hydrophilic chlorophenol ring extends in the space between dimers. Water molecules in five positions are also enclosed in the intradimer region, arranged on a plane perpendicular to the sevenfold axis of betaCD. The NMR spectroscopic studies in aqueous solution show the presence of both 1:1 and 2:1 betaCD/triclosan complexes. In the first case, two different 1:1 complexes are simultaneously present, each with either ring entering the narrow primary side of one betaCD molecule. In the 2:1 complex both rings of triclosan are included in two independent betaCD hosts, a precursor to the supramolecular arrangement found in the crystalline form. In the case of the negatively charged sodium heptakis[6-deoxy-6-(3-thiopropionate)]-betaCD, the NMR studies at pH 7.9 show a complete inclusion of triclosan inside the host in two orientations, one for the non-ionized (phenol) and reverse for the ionized (phenolate) form. Finally, for the positively charged heptakis(6-aminoethylamino-6-deoxy)-betaCD, inclusion of triclosan is possible only when the pH is raised to 10 and it is concluded that both aromatic rings are alternatively inside the cavity. However in that case also, inclusion of the entire guest in the elongated cavity is suggested.

Sensitization of europium(III) luminescence by benzophenone-containing ligands: regioisomers, rearrangements and chelate ring size, and their influence on quantum yields.

A series of europium(III) complexes based on the macrocyclic azacarboxylate structure, DO3A, have been investigated, incorporating benzophenone appended at N10 of the macrocycle via linkers containing amide bonds (H3DO3A = 1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid). Complexes [EuL(1-3)] incorporate N10-CH2CONH-BP linkers (BP = benzophenone), which allow formation of a five-membered chelate ring containing the metal ion upon chelation of the amide oxygen; these three isomeric complexes differ from one another in the substitution position of the BP unit, namely para, meta, and ortho for L1, L2, and L3 respectively. The quantum yields of europium luminescence sensitized via the chromophore are found to be highly dependent upon the position of substitution, being 20 times smaller for the ortho compared to the para-substituted complex. A related para-substituted BP complex [EuL(4)], prepared by an unusual Michael reaction of the azamacrocycle with a BP-containing acrylamide, incorporates an additional methylene unit in the linker, namely N10-CH2CH2CONH-BP. Despite the longer linker, this complex equals the luminescence quantum yield achieved with [EuL(1)] (Phi(lum) = 0.097 and 0.095, respectively, in H2O at 298 K). Analysis of the pertinent kinetics reveals that the decreased energy transfer efficiency in this complex, arising from the longer donor-acceptor distance, is compensated by an increased radiative rate constant. Under basic conditions, the ortho-substituted complex [EuL(3)] undergoes an intramolecular rearrangement to generate an unprecedented complex [EuL(5)] incorporating a 4-phenyl-2-hydroxyquinoline unit directly bound to the ring nitrogen. Although this complex is a poor emitter, an analogous complex obtained from 2-amino-acetophenone, which generates 4-methyl-2-hydroxyquinoline during the corresponding rearrangement, is an order of magnitude more emissive while still benefiting from relatively long-wavelength absorption. The emission from this complex is pH sensitive, being dramatically quenched under mildly basic conditions.

Positive effect of natural and negatively charged cyclodextrins on the stabilization of penicillins towards beta-lactamase degradation due to inclusion and external guest-host association. An NMR and MS study.

The complexation of penicillin (1a-c) and cephalosporin (2a,b) antibiotics with cyclodextrins (CDs), both natural [beta-CD (3b) and gamma-CD (3c)] and carboxylated [heptakis(6-oxycarbonylethylthio-6-deoxy)-beta-CD sodium salt (4b) and octakis(6-oxycarbonylethylthio-6-deoxy)-gamma-CD (4c) sodium salt], has been studied at neutral pH. Penicillins [ampicillin (1a), amoxicillin (1b) and dicloxacillin (1c) form inclusion complexes with the above CDs, as was shown by extensive NMR spectroscopic studies, whereas cephalosporins (cephalexin, cefadroxil) do not. Inclusion of the penicillins into either 3b or 4b was not accompanied by significant chemical shift changes in the 1H NMR spectra. On the contrary, with the wider 3c and its derivative 4c inclusion was evidenced by both chemical shift displacements of the cavity protons and intermolecular interactions, indicating the formation of primarily 1:1 guest-host inclusion complexes. The binding constants for 1a/3c, 1a/4c and 1c/3c were calculated as 19 +/- 4, 17 +/- 0.9 and 622 +/- 200 M(-1), respectively. With 4c, a 1:2 stoichiometry was also found. In addition, simultaneous formation of aggregates by external association takes place in solution, as shown by the ESI-mass spectrometric data. Studies on the hydrolysis of ampicillin under pseudo-first order conditions using an excess of 3c, 4c and of linear maltoheptaose at pH 7 showed that the drug hydrolysed at a similar rate in all cases. In the presence, however, of beta-lactamase enzyme and the carboxylated host 4c, ampicillin degraded twice as slowly (0.008 h(-1)) as in the presence of beta-lactamase alone (0.017 h(-1)). This was explained by the effective protection provided by both inclusion and external association of the host. The interaction, therefore, of penicillins with carboxylated CDs may present a means to lessen the chemical instability of these drugs in the presence of beta-lactamase enzymes.