Ln(III) complexes of macrocyclic ligands are used in medicinal chemistry, for example as contrast agents in MRI or radiopharmaceutical compounds, and in diagnostics using fluorescence imaging. This paper is devoted to a spectroscopic study of Ln(III) ternary complexes consisting of macrocyclic heptadentate DO3A and bidentate 3-isoquinolinate (IQCA) ligands. IQCA serves as an efficient antenna ligand, leading to a higher quantum yield and Stokes shift (250-350 nm for Eu, Tb, Sm, Dy in VIS region, 550-650 nm for Yb, Nd in NIR region). The shielding-quenching effect of NAD(P)H on the luminescence of the Ln(III) ternary complexes was investigated in detail and this phenomenon was utilized for the analytical determination of this compound. This general approach was verified through an enzymatic reaction during which the course of ethanol transformation catalyzed by alcohol-dehydrogenase (ADH) was followed by luminescence spectroscopy. This method can be utilized for selective and sensitive determination of ethanol concentration and/or ADH enzyme activity. This new analytical method can also be used for other enzyme systems coupled with NAD(P)H/NAD(P)+ redox pairs.

• Klíčová slova
• Ln(III) complexes, Ln(III) luminescence in VIS/NIR range, NAD(P)H determination, antenna ligand, enzyme probe, macrocyclic ligands,
• MeSH
• alkoholdehydrogenasa chemie   MeSH
• ethanol chemie   MeSH
• katalýza MeSH
• kontrastní látky chemie   MeSH
• lanthanoidy chemie   MeSH
• ligandy MeSH
• luminiscence * MeSH
• molekulární struktura MeSH
• NADP analýza   MeSH
• oxidace-redukce MeSH
• radiofarmaka chemie   MeSH
• spektrofotometrie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkoholdehydrogenasa MeSH
• ethanol MeSH
• kontrastní látky MeSH
• lanthanoidy MeSH
• ligandy MeSH
• NADP MeSH
• radiofarmaka MeSH

Three 1,4,7,10-tetraazacyclododecane-based ligands disubstituted in 1,4-positions with phosphonic acid, phosphonate monoethyl-ester, and H-phosphinic acid pendant arms, 1,4-H4do2p, 1,4-H2do2pOEt, and 1,4-H2Bn2do2pH, were synthesized and their coordination to selected metal ions, Mg(II), Ca(II), Mn(II), Zn(II), Cu(II), Eu(III), Gd(III), and Tb(III), was investigated. The solid-state structure of the phosphonate ligand, 1,4-H4do2p, was determined by single-crystal X-ray diffraction. Protonation constants of the ligands and stability constants of their complexes were obtained by potentiometry, and their values are comparable to those of previously studied analogous 1,7-disubstitued cyclen derivatives. The Gd(III) complex of 1,4-H4do2p is ~1 order of magnitude more stable than the Gd(III) complex of the 1,7-analogue, probably due to the disubstituted ethylenediamine-like structural motif in 1,4-H4do2p enabling more efficient wrapping of the metal ion. Stability of Gd(III)-1,4-H2do2pOEt and Gd(III)-H2Bn2do2pH complexes is low and the constants cannot be determined due to precipitation of the metal hydroxide. Protonations of the Cu(II), Zn(II), and Gd(III) complexes probably takes place on the coordinated phosphonate groups. Complexes of Mn(II) and alkali-earth metal ions are significantly less stable and are not formed in acidic solutions. Potential presence of water molecule(s) in the coordination spheres of the Mn(II) and Ln(III) complexes was studied by variable-temperature NMR experiments. The Mn(II) complexes of the ligands are not hydrated. The Gd(III)-1,4-H4do2p complex undergoes hydration equilibrium between mono- and bis-hydrated species. Presence of two-species equilibrium was confirmed by UV-Vis spectroscopy of the Eu(III)-1,4-H4do2p complex and hydration states were also determined by luminescence measurements of the Eu(III)/Tb(III)-1,4-H4do2p complexes.

• Klíčová slova
• MRI contrast agents, copper, cyclen derivatives, gadolinium, macrocyclic ligands, manganese, metal complexes, phosphinate ligands, phosphonate ligands, protonation constants, stability constants,
• MeSH
• cyklamy MeSH
• europium chemie   MeSH
• gadolinium chemie   MeSH
• heterocyklické sloučeniny chemie   MeSH
• komplexní sloučeniny chemická syntéza   chemie   MeSH
• kontrastní látky MeSH
• krystalografie rentgenová MeSH
• kyseliny fosfinové chemie   MeSH
• ligandy MeSH
• magnetická rezonanční spektroskopie MeSH
• mangan chemie   MeSH
• organofosfonáty chemie   MeSH
• potenciometrie MeSH
• spektrofotometrie ultrafialová MeSH
• teplota MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyclen MeSH Prohlížeč
• cyklamy MeSH
• ethyl phosphonate MeSH Prohlížeč
• europium MeSH
• gadolinium MeSH
• heterocyklické sloučeniny MeSH
• komplexní sloučeniny MeSH
• kontrastní látky MeSH
• kyseliny fosfinové MeSH
• ligandy MeSH
• mangan MeSH
• organofosfonáty MeSH

OBJECTIVE: 19F MRI requires biocompatible and non-toxic soluble contrast agents with high fluorine content and with suitable 19F relaxation times. Probes based on a DOTP chelate with 12 magnetically equivalent fluorine atoms (DOTP-tfe) and a lanthanide(III) ion shortening the relaxation times were prepared and tested. METHODS: Complexes of DOTP-tfe with trivalent paramagnetic Ce, Dy, Ho, Tm, and Yb ions were synthetized and characterized. 19F relaxation times were determined and compared to those of the La complex and of the empty ligand. In vitro and in vivo 19F MRI was performed at 4.7 T. RESULTS: 19F relaxation times strongly depended on the chelated lanthanide(III) ion. T1 ranged from 6.5 to 287 ms, T2 from 3.9 to 124.4 ms, and T2* from 1.1 to 3.1 ms. All complexes in combination with optimized sequences provided sufficient signal in vitro under conditions mimicking experiments in vivo (concentrations 1.25 mM, 15-min scanning time). As a proof of concept, two contrast agents were injected into the rat muscle; 19F MRI in vivo confirmed the in vivo applicability of the probe. CONCLUSION: DOTP-based 19F probes showed suitable properties for in vitro and in vivo visualization and biological applications. The lanthanide(III) ions enabled us to shorten the relaxation times and to trim the probes according to the actual needs. Similar to the clinically approved Gd3+ chelates, this customized probe design ensures consistent biochemical properties and similar safety profiles.

• Klíčová slova
• Fluorine-19 magnetic resonance imaging, Lanthanide series elements, Macrocyclic ligand complexes, Molecular probes, Phosphinic acid complexes, Relaxation times,
• MeSH
• chelátory chemie   MeSH
• fluor chemie   MeSH
• ionty MeSH
• kontrastní látky chemie   MeSH
• krysa rodu Rattus MeSH
• lanthanoidy chemie   MeSH
• ligandy MeSH
• magnetismus MeSH
• molekulová hmotnost MeSH
• oxazoly chemie   MeSH
• pyrimidinony chemie   MeSH
• zobrazování fluorovou magnetickou rezonancí * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 2,3-dihydro-5H-oxazolo(3,2-a)thieno(3,2-d)pyrimidin-5-one MeSH Prohlížeč
• chelátory MeSH
• fluor MeSH
• ionty MeSH
• kontrastní látky MeSH
• lanthanoidy MeSH
• ligandy MeSH
• oxazoly MeSH
• pyrimidinony MeSH

Lanthanide(III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (H(3)DO3A) are suggested as sensors for sensitive luminescence-based determination of a carbonate anion. Thermodynamic study of association of [Eu(H(2)O)(2)(DO3A)] with bidentate anionic ligands using luminescence spectroscopy reveals an affinity order CO(3)(2-) > oxalate(2-) > picolinate(-) > phthalate(2-) ≈ citrate(3-); presumably as a consequence of an increasing chelate ring size. The ternary [Eu(DO3A)(picolinate)](-) and [Tb(DO3A)(picolinate)](-) complexes show improved photophysical properties due to the antenna effect of the picolinate anion. High quenching effect of carbonate anion and, to a lesser extent also oxalate, enables construction of a linear calibration plot utilizing optimized experimental conditions (e.g. c(LnL) = 0.1 mM, c(picolinate) = 2-5 mM, pH = 7.4, λ(exc) = 286 nm, etc.) for carbonate determination in solution. Both sensors show a comparable sensitivity and the detection limit of about 0.4 mM. In order to improve the photophysical properties of Ln(III) sensor by shift of excitation wavelength about 40 nm to VIS range, the isoquinoline-3-carboxylic acid (IQCA) as antenna ligand was employed instead of picolinic acid. The analysis of commercial samples of European mineral waters was carried out and they were compared to the results obtained by capillary isotachophoresis to confirm there is no inherent (systematic) error to the present analysis. The Ln(III) sensor with IQCA is recommended since it has a better robustness than that with picolinate. The present analytical method is simple and rapid, and it is useful for sensitive determination of bicarbonate/carbonate concentration in water samples under aerobic conditions.

• MeSH
• chemické techniky analytické přístrojové vybavení   MeSH
• europium chemie   MeSH
• heterocyklické sloučeniny monocyklické chemie   MeSH
• ligandy MeSH
• luminiscenční měření MeSH
• makrocyklické sloučeniny chemie   MeSH
• organokovové sloučeniny chemie   MeSH
• terbium chemie   MeSH
• termodynamika MeSH
• uhličitany analýza   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid MeSH Prohlížeč
• europium MeSH
• heterocyklické sloučeniny monocyklické MeSH
• ligandy MeSH
• makrocyklické sloučeniny MeSH
• organokovové sloučeniny MeSH
• terbium MeSH
• uhličitany MeSH