Development of a borondipyrromethene-based Zn2+ fluorescent probe: solvent effects on modulation sensing ability

A borondipyrromethene-based Zn(2+) fluorescent probe BODPAQ was designed and synthesized. The chelators in BODPAQ, 2,2'-dipicolylamine (DPA) and 8-aminoquinoline (AQ), coordinate to Zn(2+) in a synergic manner. As a result, BODPAQ displays high Zn(2+) selectivity with a dramatic enhanced emission accompanied by a notable hypsochromic shift due to the binary inhibition effect of PET and ICT mechanisms, enabling the detection of Zn(2+) by both ratiometric and normal turn-on fluorescence methods in acetonitrile. Interestingly, the sensitivity of BODPAQ towards Zn(2+) changes upon varying the compositions of buffer solutions. In 3-morpholinopropanesulfonic acid (MOPS) buffer aqueous solution (50% CH(3)CN), BODPAQ displays the highest sensitivity for Zn(2+), while in citrate-phosphate buffer, BODPAQ shows no response to Zn(2+).     

Balance between fluorescence enhancement and association affinity in fluorescent heteroditopic indicators for imaging zinc ion in living cells

A fluorescent heteroditopic indicator for the zinc(II) ion possesses two different zinc(II) binding sites. The sequential coordination of zinc(II) at the two sites can be transmitted into distinct fluorescence changes. In the heteroditopic ligand system that our group developed, the formations of mono- and dizinc(II) complexes along an increasing gradient of zinc(II) concentration lead to fluorescence enhancement and an emission bathochromic shift, respectively. The extents of these two changes determine the sensitivity and, ultimately, the effectiveness of the heteroditopic indicator in quantifying zinc(II) ion over a large concentration range. In this work, a strategy to increase the degree of fluorescence enhancement upon the formation of the monozinc(II) complex of a heteroditopic ligand under simulated physiological conditions is demonstrated. Fluorination of the pyridyl groups in the pentadentate N,N,N'-tris(pyridylmethyl)ethyleneamino group reduces the apparent pK(a) value of the high-affinity site, which increases the degree of fluorescence enhancement as the monozinc(II) complex is forming. However, fluorination impairs the coordination strength of the high-affinity zinc(II) binding site, which in the triply fluorinated ligand reduces the binding strength to the level of the low-affinity 2,2'-bipyridyl. The potential of the reported ligands in imaging zinc(II) ion in living cells was evaluated. The subcellular localization properties of two ligands in five organelles were characterized. Both benefits and deficiencies of these ligands were revealed, which provides directions for the near future in this line of research.     

Photochemically stable fluorescent heteroditopic ligands for zinc ion

Photochemically stable fluorescent heteroditopic ligands (9 and 10) for zinc ion were prepared and studied. Two independent metal coordination-driven photophysical processes, chelation-enhanced fluorescence (CHEF) and internal (or intramolecular) charge transfer (ICT), were designed into our heteroditopic ligand framework. This strategy successfully relates three coordination states of a ligand, non-, mono-, and dicoordinated, to three fluorescence states, fluorescence OFF, ON at one wavelength, and ON at another wavelength. This ligand platform has provided chemical foundation for applications such as the quantification of zinc concentration over broad ranges (Zhang, L.; Clark, R. J.; Zhu, L. Chem.-Eur. J. 2008, 14, 2894-2903) and molecular logic functions (Zhang, L.; Whitfield, W. A.; Zhu, L. Chem. Commun. 2008, 1880-1882). The binding stoichiometries of dipicolylamino and 2,2'-bipyridyl, the two binding sites featured in heteroditopic ligands 7-10, were studied in acetonitrile using both Job's method of continuous variation and isothermal titration calorimetry (ITC). The fluorescence enhancement of 7-10 upon the formation of monozinc complexes (defined as the fluorescence quantum yield ratio of monozinc complex and free ligand) is qualitatively related to the highest occupied molecular orbital (HOMO) energy levels of their fluorophores. This is consistent with our hypothesis on the thermodynamics of the coordination-driven photophysical processes embodied in the designed heteroditopic system, which was supported by cyclic voltammetry studies. In conclusion, compounds 9 and 10 not only possess better photochemical stability but also display a higher degree of fluorescence turn-on upon formation of monozinc complexes than their vinyl counterparts 7 and 8.     

A heteroditopic fluoroionophoric platform for constructing fluorescent probes with large dynamic ranges for zinc ions

A heteroditopic fluoroionophoric platform has been designed for constructing fluorescent probes for zinc ions over large concentration ranges. The responses of the prototype probes 3a and 3b to zinc ions were shown to be consistent with our hypothesis, according to which the modulation of photoinduced electron transfer followed by conformation rigidification or enhanced internal charge transfer of a ditopic ligand upon successive zinc coordination affords a sensitive fluorescence enhancement in one wavelength channel followed by an emission band shift to another wavelength channel. The heteroditopic arylvinyl-bipy platform established in this study provides a lead structure for constructing fluorescent probes for real-time live cell imaging of zinc ions over broad dynamic ranges.     

Photoinduced electron transfer (PET) based Zn2+ fluorescent probe: transformation of turn-on sensors into ratiometric ones with dual emission in acetonitrile

Ratiometric sensors for the detection of metal ions have gained increasing attention due to its self-calibration tendency for the environmental effects. In this context, we have synthesized and characterized a dual emitting ratiometric Zn(2+) probe (1) having acridinedione as a fluorophore and N,N-bis(2-pyridylmethyl)amine (BPA) as a receptor unit. Existence of two different conformation of the molecule with photoinduced electron transfer (PET) from amine moiety to the acridinedione fluorophore leads to dual emission, namely locally excited (425 nm) and anomalous charge transfer emission (560 nm) in aprotic solvents. In the presence of one equivalent of Zn(2+), a 15-fold fluorescence enhancement in the locally excited state together with the quenching of charge transfer emission is observed. The intensity changes at the two emission peaks allow a ratiometric detection of Zn(2+) under PET signaling mechanism. The utilization of PET process for the ratiometric fluorescence change will further signify the importance of PET mechanism in sensing action. Addition of Zn(2+) to 1 in acetonitrile/water mixtures shows a single emission peak with fluorescence enhancement.     

Spectral properties of intramolecular charge transfer fluorescence probe 1-keto-2-(p-dimethylaminobenzal)-tetrahydronaphthalene

The photophysical properties of a new compound 1-keto-2-(p-dimethylaminobenzal)-tetrahydronaphthalene in various solvents at room temperature were characterized by the absorption and steady-state fluorescence technique. The bathochromic shift on the emission spectra, the broad halfwidth of the fluorescence band and the increase in the excited state dipole moment occurred. These results gave the evidence about the intramolecular charge transfer (ICT) character in the emitting singlet state of the compound.     

Photophysics of the platinum(II) terpyridyl terpyridylacetylide platform and the influence of Fe(II) and Zn(II) coordination

The synthesis, structural characterization, and photoluminescence (PL) properties of the square-planar terpyridylplatinum(II) complex [ ( t )Bu 3tpyPtCCtpy] (+) ( 1) and the octahedral trinuclear Fe (II) and Zn (II) analogues [Fe( ( t )Bu 3tpyPtCCtpy) 2] (4+) ( 2) and [Zn( ( t )Bu 3tpyPtCCtpy) 2] (4+) ( 3) are described. The photophysical properties of the mononuclear Pt (II) complex 1 are consistent with a charge-transfer excited-state parentage producing a large Stokes shift with a concomitant broad, structureless emission profile. The Fe-based ligand-field states in 2 provide an efficient nonradiative deactivation pathway for excited-state decay, resulting in a nonemissive compound at room temperature. Interestingly, upon chelation of 1 with Zn (II), a higher energy charge-transfer emission with a low-energy shoulder and a 215 ns excited-state lifetime is produced in 3. A spectroscopically identical species relative to 3 was produced in control experiments when 1 was reacted with excess protons (HClO 4) as ascertained by UV-vis and static PL spectra measured at room temperature and 77 K. Therefore, the chelation of Zn (II) to 1 is acid-base in nature, and its Lewis acidity renders the highest occupied molecular orbital level in 1 much less electron-rich, which induces a blue shift in both the absorption and emission spectra. At 77 K, complexes 1, 3, and protonated 1 display at least one prevalent vibronic component in the emission profile (1360 cm (-1)) resembling PL emanating from a ligand-localized excited-state, indicating that these emitting states are inverted relative to room temperature. These results are qualitatively confirmed by the application of time-dependent theory using only the 1360 cm (-1) mode to reproduce the low-temperature emission spectra.     

Synthesis and characterizations of star-shaped octupolar triazatruxenes-based two-photon absorption chromophores

A series of star-shaped octupolar triazatruxenes (TATs, 1-6) with intramolecular "push-pull" structure were synthesized and their photophysical properties have been systematically investigated. These chromophores showed obvious solvatochromic effect, i.e., significant bathochromic shift of the emission spectra and larger Stokes shifts were observed in more polar solvents mainly due to photoinduced intramolecular charge transfer (ICT). The two-photon absorption (2PA) cross-section values were determined by two-photon excited fluorescence (2PEF) measurements in toluene and THF. These chromophores exhibited large two-photon absorption cross-sections ranging from 280 to 1620 GM in the near-infrared (NIR) region. Compound 6 showed the largest 2PA action cross-section (σ(2)Φ) of 564 GM and could be a potential two-photon fluorescent (2PF) probe. In addition, compounds 1-6 all displayed good thermal stability and photostability.     

Tetrahydroindazolone substituted 2-aminobenzamides as fluorescent probes: switching metal ion selectivity from zinc to cadmium by interchanging the amino and carbamoyl groups on the fluorophore

Three fluorescent probes CdABA', CdABA and ZnABA', which are structural isomers of ZnABA, have been designed with N,N-bis(2-pyridylmethyl) ethylenediamine (BPEA) as chelator and 2-aminobenzamide as fluorophore. These probes can be divided into two groups: CdABA, CdABA' for Cd(2+) and ZnABA, ZnABA' for Zn(2+). Although there is little difference in their chemical structures, the two groups of probes exhibit totally different fluorescence properties for preference of Zn(2+) or Cd(2+). In the group of Zn(2+) probes, ZnABA/ZnABA' distinguish Zn(2+) from Cd(2+) with F(Zn)(2+)-F(Cd)(2+) = 1.87-2.00. Upon interchanging the BPEA and carbamoyl groups on the aromatic ring of the fluorophore, the structures of ZnABA/ZnABA' are converted into CdABA/CdABA'. Interestingly, the metal ions selectivity of CdABA/CdABA' was switched to discriminate Cd(2+) from Zn(2+) with F(Cd)(2+)-F(Zn)(2+) = 2.27-2.36, indicating that a small structural modification could lead to a remarkable change of the metal ion selectivity. (1)H NMR titration and ESI mass experiments demonstrated that these fluorescent probers exhibited different coordination modes for Zn(2+) and Cd(2+). With CdABA' as an example, generally, upon addition of Cd(2+), the fluorescence response possesses PET pathway to display no obvious shift of maximum λ(em) in the absence or presence of Cd(2+). However, an ICT pathway could be employed after adding Zn(2+) into the CdABA' solution, resulting in a distinct red-shift of maximal λ(em).     

Zn2+-triggered excited-state intramolecular proton transfer: a sensitive probe with near-infrared emission from bis(benzoxazole) derivative

Near-infrared (NIR) emission can offer distinct advantages for biological applications. A fluorescent sensor, Zinhbo-1, based on bis(benzoxazole) ligand with 2,2'-dipicolylamine (DPA) as receptor, was synthesized. In aqueous solution, Zinhbo-1 demonstrates high sensitivity and selectivity for sensing Zn(2+) with about 10-fold enhancement and nanomolar sensitivity (K(d) = 0.29 nM). Moreover, sensor Zinhbo-1 can detect Zn(2+) in near-infrared region (over 700 nm) with large Stokes shift (ca. 230 nm) attributing to the Zn(2+)-induced excited state intramolecular proton transfer (ESIPT).     

A novel ZnII-sensitive fluorescent chemosensor assembled within aminopropyl-functionalized mesoporous SBA-15

A novel Zn2+-sensitive fluorescent chemosensor SC/SBA-15 has been obtained by the self-assembly of 4-chloroaniline-N-salicylidene (SC), a Schiff base ligand, within the channel of silylation-modified SBA-15 without destroying its hexagonally ordered mesoporous structure. The remarkable 200-fold fluorescence enhancement with a large Stokes shift of 180 nm in luminescence emission upon the addition of Zn2+ is attributed to the formation of a coordinate complex of a large rigid conjugate system and Zn2+ ions.     

Binding of H+ and Zn(II) ions with a new fluorescent macrocyclic phenanthrolinophane

The new macrocyclic ligand 1,9(4,7)-diphenanthroline-3,7,11,15-tetraazacyclohexadecaphane (L) was synthesized by a 2?:?2 reaction of 1,10-phenanthroline-4,7-dialdehyde with 1,3-diaminopropane, followed by reduction with NaBH(4). L contains two phenanthroline groups linked together by two 1,3-diaminopropane chains in such a way that the heteroaromatic nitrogen atoms point outside the ligand cavity. The ligand structure defines two pairs of identical compartments displaying a specific ability in the binding of protons (1,3-diaminopropane) and metal ions (phenanthroline). Protonation and Zn(II) coordination were studied by means of potentiometric and spectroscopic ((1)H NMR, UV-vis, fluorescence) techniques. Both protonation and Zn(II) coordination consistently affect the fluorescence emission properties of L, giving rise to enhancement or quenching of the emission, depending on the species involved. L becomes emissive upon protonation, but the formation of the highly protonated species, in particular the fully protonated [H(6)L](6+), quenches the emission. The mono- and dinuclear Zn(II) complexes of the unprotonated ligand are non-emissive, like free L, while Zn(II) binding to [HL](+) activates the emission. The most interesting aspect, however, is the chelation enhancement of quenching (CHEQ) observed upon Zn(II) binding to [H(2)L](2+) and [H(4)L](4+), being among the few examples of CHEQ effect observed for Zn(II) complexes. Hydrogen bonding between a metal coordinated water molecule and a phenanthroline group seems to be responsible for the CHEQ observed for [ZnH(2)L](4+).     

Novel fluorescent chemosensor for anions via modulation of oxidative PET: a remarkable 25-fold enhancement of emission

The fluorescence emission intensity of the 1:1 Zn(II) complex of a doubly boradiazaindacene (BODIPY) substituted bipyridyl ligand is highly sensitive to anion coordination to the metal center. Oxidative PET, which is responsible for the quenching of the fluorescence in the complex is effectively inhibited by anion coordination, leading to a 25-fold enhancement of the emission intensity.     

A ratiometric fluorescent sensor for phosphates: Zn2+-enhanced ICT and ligand competition

A pyrene-terpyridine-Zn conjugate has been synthesized and characterized, where Zn2+ acts as an electron acceptor to enhance molecular ICT with a large emission red-shift (>100 nm). It showed a ratiometric fluorescence change upon addition of phosphate anions in buffered aqueous solution. The selective response to phosphates or pyrophosphates involved ICT and ligand competition processes.     

Spectral and photophysical properties of intramolecular charge transfer fluorescence probe: 4'-dimethylamino-2,5-dihydroxychalcone

The spectral and photophysical properties of a new intramolecular charge transfer (ICT) probe, namely 4′-dimethylamino-2,5-dihydroxychalcone (DMADHC) were studied in different solvents by using steady-state absorption and emission spectroscopy. Whereas the absorption spectrum undergoes minor change with increasing polarity of the solvents, the fluorescence spectrum experiences a distinct bathochromic shift in the band position and the fluorescence quantum yield increases reaching a maximum before decrease with increasing the solvent polarity. The magnitude of change in the dipole moment was calculated based on the Lippert–Mataga equation. These results give the evidence about the intramolecular charge transfer character in the emitting singlet state of this compound.     

A novel quinoline-based two-photon fluorescent probe for detecting Cd2+ in vitro and in vivo

A new two-photon fluorescent Cd(2+) probe APQ is developed by introducing a N(1),N(1)-dimethyl-N(2)-(pyridin-2-ylmethyl)ethane-1,2-diamine binding group and a 4-methoxyphenylvinyl conjugation-enhancing group to the 2- and 6-positions of quinoline. This probe shows a large red shift and good emission enhancement under Cd(2+) binding. It also exhibits a high ion selectivity for Cd(2+) (especially over Zn(2+)) and a large two-photon absorption cross section at 710 nm. Two-photon microscopy imaging studies reveal that the new probe is non-toxic and cell-permeable and can be used to detect intracellular Cd(2+) under two-photon excitation.     

Indium(III)-induced fluorescent excimer formation and extinction in calix[4]arene-fluoroionophores

New fluorogenic or/and chromogenic calix[4]arenes 1-3 with two facing amide groups linked to fluorescent pyrene units are synthesized. Orientations of the pyrene units are remote from each other in 1 and face-to-face pi-stacked in 2, which produces different photophysical properties. In the excited state, the two pyrene units of 2 form a strong intramolecular excimer displaying an emission at 472 nm with a relatively weak monomer emission at 395 nm. In contrast, 1 exhibits only a monomer emission at 398 nm because intramolecular hydrogen bonding between the phenolic OH oxygens and the amide hydrogens prevents pi-stacking of the two pyrene groups. Fluorescence changes upon addition of various metal ions show that 1 has a remarkably high selectivity for In(3+) over the other metal ions tested. Compound 1 forms 2:1 (metal:ligand), as well as 1:1 complexes, with In(3+), with fluorescence varying uniquely with the complex stoichiometry. Compound 3, which possess two pyrene units and two chromogenic azo groups, shows almost the same binding behavior toward metal ions as does 1, together with additional bathochromic shifts of the absorption maximum. Compared with 1, compound 3 emits a considerably weaker fluorescence, which is attributed to electron transfer from the pyrene units to the nitro groups of the phenylazo moieties.     

A naphthalimide fluorophore with efficient intramolecular PET and ICT processes: application in molecular logic

A novel 4-amino-1,8-naphthalimide (NDI) with two different metal cation receptors connected at 4-amino or imide nitrogen positions respectively was designed and prepared. Significant internal charge transfer (ICT) as well as photoinduced electron transfer (PET) from the receptors to NDI is revealed by the shifted UV-vis absorption spectra and significant fluorescence quenching. Both Zn(2+) and Cu(2+) can coordinate selectively with the two cation receptors in this molecule with different affinities. The coordination of Zn(2+) with the receptor at imide nitrogen hindered the PET process and accordingly restored the quenched fluorescence of NDI. But the coordination of Zn(2+) at 4-amino position blocked the ICT process and caused significant blue-shift on the absorption peak with the fluorescence intensity unaffected. Similarly, coordination of Cu(2+) with the receptor at imide nitrogen can block the PET process, but can not restore the quenched fluorescence of compound 3 due to the paramagnetic properties of Cu(2+), which quench the fluorescence significantly instead. With Cu(2+) and Zn(2+) as two chemical inputs and absorption or fluorescence as output, several logic gate operations, such as OR, NOR and INHIBIT, can be achieved.     

Metal ion detection by luminescent 1,3-bis(dimethylaminomethyl) phenyl receptor-modified chromophores and cruciforms

Chromophores ranging from simple small molecule π-conjugated systems comprised of phenylene ethynylene or fluorenylethynyl units to cross-conjugated Bunz-type cruciforms have been derivatized to include 1,3-bis(dimethylaminomethyl)phenyl moieties. The photophysical responsiveness of these diamino-substituted chromophores to metal ions has been examined. Both emission enhancement (turn-on) and ratiometric fluorescence detection of Cu(2+) and Zn(2+) ions have been achieved in THF.     

The zinspy family of fluorescent zinc sensors: syntheses and spectroscopic investigations

Four fluorescent sensors designed for Zn(II) detection that contain a fluorescein reporting group and a pyridyl-amine-thioether derivatized ligand moiety were prepared and their photophysical properties characterized. These "Zinspy" sensors are water soluble and generally display approximately 1.4- to approximately 4.5-fold fluorescence enhancement upon Zn(II) coordination, depending upon fluorescein halogenation and the number and nature of the zinc-binding appendages. The Zinspy sensors exhibit improved selectivity for zinc compared to the di-(2-picolyl)amine-based Zinpyr family.