Search

Using intracellular-controlled photochemistry to track dynamic organelle processes is gaining attention due to its broad applications. However, most of the employed molecular probes usually require toxic photosensitizers and complex bioanalytical protocols. Here, the synthesis and performance of two new subcellular probes (

Dual-State Emission (DSE) of organic molecules in both solution and solid-state is an elusive property that has recently drawn significant interest. In this work, we report two molecular rotors 1 and 2 with exceptional photoluminescence (PL) in solution (ФPL = 0.53 and ФPL = 0.43) and in the solid state (ФPL = 0.92 and ФPL = 0.84). To the best of our knowledge, this is the first report containing Donor-pi-Acceptor-pi-Donor (D-pi-A-pi-D) compounds with high quantum yields in both states that features a rotary acceptor. Furthermore, we describe the marked variations in PL in solution upon polarity and viscosity changes. TD-DFT computations indicate that these changes are facilitated by the fast molecular rotation in these molecules. The symmetry (or lack of it) in 1 and 2 plays a crucial role in producing noticeable differences in the X-ray crystal arrays with variations in the solid-state PL. We attribute this DSE behavior to the favorable combination of the D--A--D architecture and the twisted conformations adopted in the solid state.

Dual-State Emission (DSE) of organic molecules in both solution and solid-state is an elusive property that has recently drawn significant interest. In this work, we report two molecular rotors 1 and 2 with exceptional photoluminescence (PL) in solution (ФPL = 0.53 and ФPL = 0.43) and in the solid state (ФPL = 0.92 and ФPL = 0.84). To the best of our knowledge, this is the first report containing Donor-pi-Acceptor-pi-Donor (D-pi-A-pi-D) compounds with high quantum yields in both states that features a rotary acceptor. Furthermore, we describe the marked variations in PL in solution upon polarity and viscosity changes. TD-DFT computations indicate that these changes are facilitated by the fast molecular rotation in these molecules. The symmetry (or lack of it) in 1 and 2 plays a crucial role in producing noticeable differences in the X-ray crystal arrays with variations in the solid-state PL. We attribute this DSE behavior to the favorable combination of the D--A--D architecture and the twisted conformations adopted in the solid state.

Local microviscosity monitoring in living cells is a powerful tool to determine their healthy status in either a specific organelle or in the cytosol. Here is presented the rational design of a new family of self-calibrating dual-microviscosity probes as a strategy to improve the probe response at low viscosity ranges. We found one of the probes is useful to determine low viscosity variations in living cells where subtle stiffening of the rotor group in the probe can increase its viscosity sensitivity. Further X-ray structure analysis, fluorescence anisotropic measurements, and quantum chemical calculations of the electronic excitation by means of a natural transition orbital (NTO) analysis confirmed the observed response. The present work demonstrates that small viscosity variations (0.01–0.1 cP) in cells require improved analytical sensitivity to be properly monitored.

The dual-emissive fluorescent probe described here enabled dynamic tracking of singlet oxygen (1O2)-ROS species production and localization dynamics between the mitochondria and nucleoli in the presence of agents perturbing the mitochondrial membrane potential and under a photodynamic (PDT) system. Local structural information during the probe-1O2 interaction was followed by spectrally resolved confocal microscopy.

Membrane tension pores determine organelle dynamics and functions, giving rise to physical observables during the cell death process. While fluorescent organelle-targeted probes for specific chemical analytes are increasingly available, subcellular dynamic processes involving not only chemical parameters but also physicochemical and physical parameters are uncommon. Here, we report a mitochondrial chemical probe, named RCN, rationally designed to monitor osmotic effects during transmembrane tension pore formation by using local mitochondrial polarity and a subcellular localization redistribution property of the probe. Utilizing fluorescence spectroscopy, high-resolution confocal imaging, and spectrally resolved confocal microscopy, we provide a new correlation between mitochondrial dynamics and bleb vesicle formation using osmotic pressure stimuli in the cell, where the mitochondrial local polarity was found to drastically increase. The RCN provides a reliable protocol to assess transmembrane pore formation driven by osmotic pressure increments through local polarity variations and is a more robust physicochemical parameter allowing the health and decease status of the cell to be measured.

A set of BODIPY‐carboranyl dyads synthesized by a Sonogashira cross‐coupling reaction, where different C‐substituted ortho‐ and meta‐carboranyl fragments have been linked to a BODIPY fluorophore is described. Chemical, photophysical and physicochemical analyses are presented, including NMR and SXRD experiments, optical absorption/emission studies and log P measurements. These studies, supported by DFT computations (M06‐2X/6‐31G**) provide an explanation to the largely divergent cell income that these fluorescent carboranyl‐based fluorophores display, for which a structural or physicochemical explanation remains elusive. By studying the cell uptake efficiency and subcellular localization for our set of dyads on living HeLa cells, we tracked the origins of these differences to significant variations in their static dipole moments and partition coefficients, which tune their ability to interact with lipophilic microenvironments in cells. Remarkably, m‐carboranyl‐BODIPY derivatives with a higher lipophilicity are much better internalised by cells than their homologous with o‐carborane, suggesting that m‐isomers are potentially better theranostic agents for in vitro bioimaging and boron carriers for BNCT., The work has been performed within the framework of the French-Mexican International Laboratory (LIA-LCMMC). Authors acknowledge support from PAPIIT (IN222819) and CONACyT. The work was supported by Spanish Ministerio de Economía y Competitividad, MINECO (CTQ2016-75150-R) and Generalitat de Catalunya (2017/SGR/1720). Doctoral scholarships were granted by CONACyT to P.L.-V (337958) and R. F.-C. (576635). We thank María E. Ochoa (CINVESTAV-IPN), Marco A. Leyva (CINVESTAV-IPN) and Flor R. Vega (FQ-UNAM) for NMR/HRMS experiments, SXRD experiments and technical support, correspondingly.

A multicomponent diversity-oriented synthesis of new highly emissive tetracyclic isoquinolines that target specific organelles is described. The title compounds were prepared via a three-step protocol starting with an Ugi four-component reaction, followed by either an intramolecular alkyne hydroarylation and subsequent alkene isomerization or through a Pomeranz-Fritsch-type cyclization with a final intramolecular Heck reaction. Subcellular localization studies of these compounds using green channel confocal microscopy revealed remarkable and distinctive distribution patterns in live cells, showing an unprecedented high selectivity and imaging contrast. The differentiated organelle visualization-including localizers for mitochondria, lysosomes, Golgi apparatus, endoplasmic reticulum, and plasma membrane-was achieved by varying the nature of the tetracyclic system and substituent pattern, changing the original four-component set in the starting Ugi reaction.

Small-molecule fluorescent probes having optimized optical properties, such as high photostability and brightness, local microenvironment sensitivity and specific subcellular localizations, are increasingly available. Although the basis for designing efficient fluorophores for bioimaging applications is well established, implementing an improvement in a given photophysical characteristic always tends to compromise another optical property. This problem has enormous consequences for in vivo imaging, where ensuring a specific localization and precise control of the probe response is challenging. Herein we discuss a fluorescent probe, CC334, as a case study of the chromenylium-cyanine family that commonly exhibits highly complex photophysical schemes and highly interfered bioanalytical responses. By an exhaustive and concise analysis of the CC334 optical responses including detailed spectroscopic calibrations, steady-state microenvironment effects, ultrafast photophysics analysis and computational studies, we elucidate a new strategy to apply the probe in the singlet oxygen reactive oxygen species (1O2-ROS) monitoring using in vitro and in vivo models. The probe provides a new avenue for designing fluorescent probes to understand the dynamic behavior of subcellular environments.

A dual-emissive fluorescent probe enabling dynamic changes in nuclear local microviscosity monitoring was developed. The new sensing scenario involves probe subcellular localization redistribution, allowing a quantitative analysis of the local microviscosity related to nuclear damage in the presence of agents perturbing the nuclear morphology. With the aid of an organotin(iv) in situ formed complex we propose a different scenario of bioanalytical applications through confocal microscopy.

A homologous series of dithiocarbamate ligands derived from N-substituted amino acids was reacted with different diorganotin dichlorides to give 18 diorganotin complexes. Spectroscopic and mass spectrometric analysis evidenced the formation of assemblies with six-coordinate tin atoms embedded in skewed-trapezoidal bipyramidal coordination environments of composition C2SnS2O2. Single-crystal X-ray diffraction analysis for three of the compounds revealed a one-dimensional polymeric structure for the complex with the ligand derived from 5-aminopentanoic acid, which through further intermolecular Sn···O interactions generated an overall two-dimensional coordination polymer containing 40-membered hexanuclear tin macrocycles. On the contrary, the ligands derived from 6-aminohexanoic and 8-aminooctanoic acid provided the expected 22- and 26-membered dinuclear macrocyclic structures. Density functional theory calculations for a representative series of macrocyclic complexes of composition [Me2SnLx]2 with Lx = ¯S2...

2-Phenyl-3-hydroxy-4(1H)-quinolone possessing dual fluorescence due to excited-state intramolecular proton transfer (ESIPT) forms stable complex with phenylboronic acid with blue shifted emission maximum in micellar medium of a cationic surfactant even though the compound lacks required for complexation with boronic acids cis -diol structure. No complexation is observed in the presence of neutral or anionic surfactants. Titrations of this complex with polyols including sugars and nucleotides at pH 8 displace free quinolone showing ratiometric response, which allows determination of polyols with detection limits 0.05–1 mM and unusually wide linear dynamic ranges. Another ESIPT dye 2-(2′-hydroxyphenyl)−1H-benzimidazole also lacking cis -diol structure forms equally stable complex with phenylboronic acid and allows ratiometric determination of polyols with similar characteristics. The results of this study demonstrate that blocking ESIPT of signaling molecule by complexation of the receptor with the proton donor group eliminates the low energy emission from tautomeric form but strongly enhances the high energy emission typical for “normal” form of signaling molecule creating a possibility of ratiometric sensing.

The coordination properties and acid–base behavior of 2-[{(1 S ,2 R )-1-hydroxy-1-phenylpropan-2-ylimino}methyl]-4-bromophenol Schiff base probe ( L1 ) were characterized by UV–Vis and fluorescence titrations in water. The dissociation constants for the ligand account for a keto–enamine tautomer at pH 7. Detailed complexation studies were carried out, observing the formation of stable 1:1 complex for Zn 2+ , where a “turn-on” fluorescence effect is obtained. More importantly, no Cu 2+ interference is observed, which is a typical problem for Zn 2+ probes, this is awarded to the keto–enamine tautomeric form of the probe L1 according to UV–Vis and X-ray structure data. Also, the Zn 2+ vs . Cd 2+ ion discrimination for L1 is proved. Finally, TD-DFT theoretical calculations were conducted in order to stablish the detection mechanism of the probe.

Four secondary diamines with aromatic spacer groups derived from α,α′-dibromo-p-xylene and 4,4′-bis(chloromethyl)-1,1′-biphenyl have been transformed into bis-dithiocarbamate ligands and each combined with dimethyl-, di-n-butyl-, and diphenyltin(IV) dichloride to yield a total of 12 mononuclear diorganotin(IV) bis-dithiocarbamate complexes with six-coordinate metal coordination geometries and either 23- or 27-membered macrocyclic structures. The products were fully characterized by IR and NMR (1H, 13C, 119Sn) spectroscopy and high-resolution ESI+-TOF mass spectrometry. A representative selection of the macrocyclic complexes was further examined by DFT computational studies and the relative binding energies of the cis and trans isomers of the different diorganotin complexes were calculated and compared. Additionally, four possible conformations of the trans isomers were analyzed. With the purpose of examining whether the complexes can be applied to the recognition of anions, five macrocycles were selected based on criteria that allowed the influence of the aromatic spacer group, the N substituent of the dithiocarbamate ligand, and the organic groups attached to the metal center on the recognition properties to be explored. Among the NMe4+X– salts (X– = F–, Cl–, Br–, I–, NO3–, HSO4–, and CH3COO–) examined, the diorganotin complexes were sensitive to fluoride and carboxylate anions.

Design parameters derived from structure-property relationships play a very important role in the development of efficient molecular-based functional materials with optical properties. Here, we report on the linear and nonlinear optical properties of a fluorene-derived dipolar system (DS) and its octupolar analogue (OS), in which donor and acceptor groups are connected by a phenylacetylene linkage, as a strategy to increase the number of delocalized electrons in the π-conjugated system. The optical nonlinear response was analyzed in detail by experimental and theoretical methods, showing that, in the octupolar system OS, the dipolar effects induced a strong two-photon absorption process whose magnitude is as large as 2210 GM at infrared wavelengths. Solvatochromism studies were implemented to obtain further insight on the charge transfer process. We found that the triple bond plays a fundamental role in the linear and nonlinear optical responses. The strong solvatochromism behavior in DS and OS was analyzed by using four empirical solvent scales, namely Lippert-Mataga, Kamlet-Taft, Catalán, and the recently proposed scale of Laurence et al., finding consistent results of strong solvent polarizability and viscosity dependence. Finally, the role of the acceptor groups was further studied by synthesizing the analogous compound 2DS, having no acceptor group.

Aza-flavonols are compounds containing the 3-hydroxy-4(1H)-quinolone moiety, a unique scaffold with applications expanding from fluorescent probes and bioimaging to potential metal-related pharmaceutical drugs. Compositions and stability constants of metal complexes of an aza-flavonol 1-methyl-2-phenyl-3-hydroxy-4(1H)-quinolone (LH) in aqueous micellar medium of hexadecyltrimethylammonium bromide were established by fluorescence and spectrophotometric titrations of LH in the presence of metal ions of different type at variable pH. Strong binding with quenching of ligand fluorescence was observed for Cu2+, Fe2+/3+ and Pb2+ cations. The complexation with Zn2+ induced strong fluorescence enhancement in ZnL+ complex and smaller enhancement in ZnL2 complex. Al3+, Ga3+ and Me2Sn2+ cations induced strong fluorescence enhancement in 1:1 ML complexes, but quenching in ML2 complexes. Together with the relevant literature data these results indicate that the quenching effect in 1:2 complexes along with strong fluorescence enhancement in respective 1:1 complexes is a general phenomenon for 3-hydroxypyranone and 3-hydroxypyridinone ligands. The quantum mechanical Natural Transition Orbital analysis of ground and excited states of LH, AlL2+ and AlL2+ species reveals that the fluorescence of AlL2+ complex is quenched by an internal electron transfer process, which is absent in the 1:1 AlL2+ complex. The results emphasize strong dependence of the coordination induced fluorescence changes on the complex composition.

The dual-emissive fluorescent probe described here enabled dynamic tracking of singlet oxygen (1O2)-ROS species production and localization dynamics between the mitochondria and nucleoli in the presence of agents perturbing the mitochondrial membrane potential and under a photodynamic (PDT) system. Local structural information during the probe-1O2 interaction was followed by spectrally resolved confocal microscopy.

The measurement of physicochemical parameters in living cells can provide information specific to individual cell organelles, helping us to understand subcellular function in health and disease. While organelle-specific chemical probes have allowed qualitative measurements of micropolarity or microviscosity in organelles such as the mitochondria, the simultaneous quantification of mitochondrial local microviscosity (η(m)) and micropolarity (ε(m)), along with structural concurrent structural variations, has remained an unmet need. Here, we describe a new multifunctional mitochondrial probe (MMP) for simultaneous monitoring of η(m) and ε(m). This new probe enabled highly precise, quantitative measurements of local mitochondrial microviscosity and micropolarity in the presence of a variety of agents perturbing cellular function, and the changes observed using the probe could also be correlated with alterations in mitochondrial network morphology and motility. The strategy described represents a promising tool for the analysis of subtle changes in organellar structure.

BODIPY-derived molecular fluorescent rotors are one of the most useful families of fluorescent probes for the quantitative measurement of microviscosity. Here, we report the photophysical properties of two molecular rotors as ratiometric viscosity sensors, meso-(4-(9H-fluoren-2-yl)ethynyl)phenyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (1) and meso-(5-(9H-fluoren-2-yl)ethynyl)thiophen-2-yl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (2) having two independent chromophores; one (fluorene) is not influenced by viscosity and is used to determine concentration properties, and the other chromophore (BODIPY) acts as a molecular rotor. The fluorescence ratiometric calibration against microviscosity for the most sensitive probe (1), was obtained in a wide linear dynamic range. The sensitivity of the spectroscopic observables for 1 and 2 towards solvent viscosity and the typical analytical interfering solvent polarity and polarizability parameters were investigated by means of two different solvent scales, namely Lippert–Mataga and Catalan, finding consistent results. Quantum chemical calculations were conducted to analyze the probe mechanism in terms of Natural Transition Orbitals (NTOs) and the spatial extent of charge transfer excitations.

Nonclassical protomeric tautomerism in Schiff bases have the advantage of controlling and differentiating specific interactions in the −C═N– linkage since its interactions are not governed by keto–enol tautomerism. Here, we report about the optical properties of a Schiff base probe (P1). X-ray structure analysis evidenced the existence of an intramolecular hydrogen bond which is responsible of a photochromic-fluorescent behavior. The properties of P1 were investigated by UV–vis and fluorescence spectroscopy in solution and solid state. A positive solvatochromism resulting from specific interactions taking place in P1 was studied by three different solvent scales, namely Lippert–Mataga, Kamlet–Taft, and Catalan, finding consistent results. Moreover, a strong acidochromic behavior was detected and the pKa and pKa* values were determined, finding a photobasic character. Further, an ionochromic behavior was stablished. P1 exhibits a λ-ratiometric fluorescence response toward Sn(IV) giving a luminescence color...

A simple (R)-(−)-2-phenylglycinol functionalized Schiff base exhibited a dual response to Zn 2+ , Cu 2+ and Fe 2+ ions in water:methanol, (90:10 v/v). The compound displays an “off–on” fluorescent effect with Zn 2+ ions. The emission response decreased with Cu 2+ forming a Cu 2+ /Zn 2+ specie. The fluorescence signal is restored upon addition of sulfide anion (S 2 − ) using the Cu 2+ displacement approach , forming again the Zinc complex. Additionally, the sensor exhibits a second channel (colorimetric) response with Fe 2+ even in the presence of competing Fe 3+ ions. The pH profiles allowed to determine the p K a values and the pH-dependent change in the sensor recognition process. In addition, TD-DFT quantum chemical calculations were implemented to analyze the sensing mechanism by means of Natural Transition Orbital (NTO) analysis. Flow cytometry experiments demonstrated that the sensor successfully detects either exogenous or endogenous (natural) Zn 2+ ions in Jurkat cells with high sensitivity.

The acid–base and coordination properties of 2-phenyl-3-hydroxy-4(1H)-quinolone (1) and 1-methyl-2-phenyl-3-hydroxy-4(1H)-quinolone (2) were characterized by potentiometric, UV-Visible and fluorescence titrations in water containing 5 or 30% vol MeCN and in a micellar solution of a cationic surfactant. The first dissociation constants (pKa1) corresponding to OH deprotonation of 1 and 2 are about 10 and ligand 1 undergoes a second NH deprotonation with a pKa2 about 12, which is reduced to 10.4 in the presence of a cationic surfactant. More detailed complexation studies were performed with more soluble ligand 1, which forms stable complexes of 1:1 and 1:2 compositions with Fe(III), Cu(II), Zn(II), Pb(II) and Me2Sn(IV) cations in neutral solutions. The most unusual behavior is observed with Zn(II), which strongly promotes NH deprotonation of ligand 1 with formation of the Zn(L)22− complex at a pH about 8. The formation of this complex is confirmed by the results of 1H NMR titrations in DMSO-d6. Binding of all cations is accompanied by the appearance of a new absorption band in the range 385–405 nm with concomitant disappearance of the band at 350–360 nm in the free ligand. Interactions of 1 and 2 with Zn(II) and Me2Sn(IV) are accompanied by strong and selective fluorescence enhancements with the blue shift of the emission bands allowing ratiometric detection of these cations. Complexation with transition and heavy metal ions as well as with lanthanides induces fluorescence quenching. Ligand 2 is characterized by X-ray crystallography.

Seven Schiff base derivatives of 4-dimethylamino-trans-cinnamaldehyde were synthesized in good yield. The structures of all new derivatives were established by IR, 1H, 13C NMR and HRMS experiments and three of them were corroborated by X-ray diffraction studies. Analysis of the supramolecular structures evidenced the presence of strong intermolecular hydrogen bonds (O–H⋯N) which promote the formation of molecular chains. The linear properties of this series of chromophores were investigated by UV-Vis and fluorescence spectroscopy in solution and in the solid state. The results revealed interesting photochromic properties for compound 2a promoted by a hydrogen bonding interaction in the solid state, which was established by absorption and emission spectra. Further evidence of the specific interactions that take place in compound 2a was obtained by studying the solvent effects observing a solvato- and acidochromic behavior.

A simple ( R )-(−)-2-phenylglycinol functionalized Schiff base L1 and its characterization as a fluorescent–colorimetric sensor for Hg 2+ ion are described. The UV–vis and fluorescence analysis in methanol and aqueous solution show complex formation between L1 and Hg 2+ ion with a micromolar association constant. Competition experiments performed for the acetate salts of Hg 2+ , Zn 2+ , Co 2+ , Pb 2+ , Cd 2+ , Mn 2+ , Cu 2+ , Ni 2+ , and Ba 2+ revealed that compound L1 exhibits high selectivity toward Hg 2+ displaying a color change easily detectable by naked-eye and a turn-off fluorescent effect due to a chelation-enhanced quenching (CHEQ) mechanism. Moreover, addition of EDTA to L1 –Hg 2+ recovers the fluorescence and color offering receptor L1 as a reversible sensor for real-time applications.

The synthesis, chemical characterization and optical studies of three novel fluorene derivatives is reported. These compounds comprise a D–A–D architecture with fluorene moieties as donor groups and fluorenone or benzothiadiazole derivatives as acceptor groups. Theoretical analysis confirmed the existence and the nature of two principal electronic transitions (π → π* and intramolecular charge transfer). Spectroscopic studies in solution revealed that the intramolecular charge transfer character, and in turn the two-photon activity i.e., the fluorescence induced by two-photon absorption, is strongly affected by solvent polarity. The influence of specific solvent–solute interactions over emission properties was also studied through Lippert–Mataga plot. Evaluation of the two-photon absorption cross-sections, gave a maximum value of 105 GM (1 GM = 10−50 cm4 s) in toluene and a minimum value of 23 GM in THF solutions at 750 nm for the fluorenone derivative, a molecule with poor intramolecular charge transfer character and thus weak two-photon absorption; however the benzothiadiazole derivative, with stronger intramolecular charge transfer transition, produced a maximum value of 1000 GM in THF and a minimum value of 236 GM in methanol. Fluorescence quantum efficiency of these compounds was also affected by the medium, with fluorescence quenching in protic solvents such as methanol due to specific solvent interactions (i.e., hydrogen-bonding). Nevertheless, in a more polar medium such as water, nanoaggregates synthesized from the benzothiadiazole derivative exhibited good two-photon activity, i.e., ∼500 GM and fluorescence quantum efficiency of 0.83. Furthermore, these nanoaggregates exhibited more resistance against photodegradation processes than any of the organic solutions tested.

Non-classical protomerism of Schiff bases offers several advantages; for example, specific interactions in the -C[double bond, length as m-dash]N- linkage can be controlled and differentiated because the interactions are not governed by keto-enol tautomerism. Herein, the pH sensing properties of a new protomeric Schiff base probe () are reported. In particular, among several acids, the probe displays significant optical responses upon interaction with hydrochloric acid (HCl). X-ray structural analysis confirmed the existence of an intermolecular interaction with HCl through a -C[double bond, length as m-dash]NH-ClO- linkage. Moreover, an optical response via a second channel is manifested as photochromic fluorescence behavior. The properties of were investigated by UV-vis and fluorescence spectroscopy in a solution and the solid state. Its strong acidofluorochromic behavior was analyzed and its pKa and values were determined, which revealed a photobasic character. Positive solvatochromism that resulted from specific interactions taking place in was studied using four different solvent scales, namely, Lippert-Mataga, Kamlet-Taft, Catalán and the recently proposed scale of Laurence et al., which yielded consistent results. Finally, theoretical calculations were conducted to analyze the mechanism of the probe in terms of natural transition orbitals (NTOs) and the spatial extent of charge transfer excitations.

Two simple and low cost 2,4-di-tert-butyl-6-[(1-hydroxycyclohexylmethylimino)methyl]phenol (L1) and 2-[{(1-hydroxycyclohexyl)methylimino}methyl]phenol (L2) Schiff base sensors exhibiting selectivity for Zn(2+) in water:methanol (95:5, v/v, 10 mM HEPES) are described. L1 and L2 display an "off-on" fluorescence effect forming the L1·Zn and L2·Zn complexes, respectively. In the case of L1·Zn, the emission response is quenched by the addition of Cu(2+) forming the respective L1·Cu complex; in spite of that, the fluorescence signal can be completely restored only by the addition of tartrate anions (C4H4O6(2-)) forming again L1·Znvia the "off-on" displacement approach. However, in the case of L2·Zn no Cu(2+) interference is observed, which is a typical problem for Zn(2+) sensors. Here we describe that a very subtle structural change in the ligand during transition from the enol-imine tautomer in L1 to the keto-enamine tautomer in L2 is enough to modulate the Zn(2+)/Cu(2+) selectivity. Also, the Zn(2+)vs. Cd(2+) discrimination for L1 and L2 is proved. Moreover, we found that the interaction between both L·Zn complexes and tartrate anions completely restored the free ligands by the ligand substitution mechanism even in a more efficient association than phosphate anions. Further, a second colorimetric response channel upon addition of Fe(2+) was observed for L1 and L2. Then, TD-DFT theoretical calculations were conducted in order to study the efficiency of the sensors to give different responses in the presence of such metal ions. Finally, the L2 sensor successfully detects Zn(2+) in Jurkat cells cultured with and without Zn(2+) enriched medium.