Dansyl - naphthalimide dyads as molecular probes: effect of spacer group on metal ion binding properties

Interaction of a few dansyl-naphthalimide conjugates 1a-e linked through polymethylene spacer groups with various metal ions was investigated through absorption, fluorescence, NMR, isothermal calorimetric (ITC), and laser flash photolysis techniques. The characteristic feature of these dyads is that they exhibit competing singlet-singlet energy transfer (SSET) and photoinduced electron transfer (PET) processes, both of which decrease with the increase in spacer length. Depending on the spacer group, these dyads interact selectively with divalent Cu2+ and Zn2+ ions, as compared to other mono- and divalent metal ions. Jobs plot analysis showed that these dyads form 2:3 complexes with Cu2+ ions, while 1:1 complexes were observed with Zn2+ ions. The association constants for the Zn2+ and Cu2+ complexes were determined and are found to be in the order 103-105 M-1. Irrespective of the length of the spacer group, these dyads interestingly act as fluorescence ratiometric molecular probes for Cu2+ ions by altering the emission intensity of both dansyl and naphthalimide chromophores. In contrast, only the fluorescence intensity of the naphthalimide chromophore of the lower homologues (n = 1-3) was altered by Zn2+ ions. 1H NMR and ITC measurements confirmed the involvement of both sulfonamide and dimethylamine groups in the complexation with Cu2+ ions, while only the latter group was involved with Zn2+ ions. Laser excitation of the dyads 1a-e showed formation of a transient absorption which can be attributed to the radical cation of the naphthalimide chromophore, whereas only the triplet excited state of the dyads 1a-e was observed in the presence of Cu2+ ions. Uniquely, the complexation of 1a-e with Cu2+ ions affects both PET and SSET processes, while only the PET process was partially inhibited by Zn2+ ions in the lower homologues (n = 1-3) and the higher homologues exhibited negligible changes in their emission properties. Our results demonstrate that the spacer length dependent variations of the photophysical properties of these novel conjugates not only enable the selective detection of Cu2+ and Zn2+ ions but also aid in discriminating these two biologically important metal ions

DNA-assisted long-lived excimer formation in a cyclophane

A color-changed sandwich: A novel water-soluble cyclophane containing anthracene and imidazolium moieties (see structure) exhibits dual emission in aqueous medium and undergoes sequence-selective interactions with DNA but not with proteins and micelles. In the presence of DNA, it forms a sandwich-type excimer, which exhibits an unusually long lifetime (T) and red-shifted emission. This cyclophane can be used for DNA recognition through "turned on" excimer emission

Development of new photosensitizers for photodynamic therapy

In the photo-dynamic therapy (PDT) uses it, that certain compounds, called photosensitizers, for cells only in the light toxicity. Thus, for example, tumor cells are killed in the organism targeted. This could be particularly successful if it succeeds, with the photosensitizers before light exposure selectively transport into tumor cells and then be killed to enrich

Novel bifunctional acridine-acridinium conjugates: synthesis and study of their chromophore-selective electron-transfer and DNA-binding properties

Novel bifunctional conjugates 1-3, with varying polymethylene spacer groups, were synthesized, and their DNA interactions have been investigated by various biophysical techniques. The absorption spectra of these systems showed bands in the regions of 300-375 and 375-475 nm, corresponding to acridine and acridinium chromophores, respectively. When compared to 1 (φf = 0.25), bifunctional derivatives 2 and 3 exhibited quantitative fluorescence yields (φf = 0.91 and 0.98) and long lifetimes (τ = 38.9 and 33.2 ns). The significant quenching of fluorescence and lifetimes observed in the case of 1 is attributed to intramolecular electron transfer from the excited state of the acridine chromophore to the acridinium moiety. DNA-binding studies through spectroscopic investigations, viscosity, and thermal denaturation temperature measurements indicate that these systems interact with DNA preferentially through intercalation of the acridinium chromophore and exhibit significant DNA association constants (KDNA = 105-107 M−1). Compound 1 exhibits chromophore-selective electron-transfer reactions and DNA binding, wherein only the acridinium moiety of 1 interacts with DNA, whereas optical properties of the acridine chromophore remain unperturbed. Among bifunctional derivatives 2 and 3, the former undergoes DNA mono-intercalation, whereas the latter exhibits bis-intercalation; however both of them interact through mono-intercalation at higher ionic strength. Results of these investigations demonstrate that these novel water-soluble systems, which exhibit quantitative fluorescence yields, chromophore-selective electron transfer, and DNA intercalation, can have potential use as probes in biological applications

Chiral supramolecular assemblies of a squaraine dye in solution and thin films: concentration-, temperature-, and solvent-induced chirality inversion

We prepared novel cholesterol-appended squaraine dye 1 and model squaraine dye 2 and investigated their aggregation behavior in solution and thin films using photophysical, chiroptical, and microscopic techniques. Investigations on the dependence of aggregation on solvent composition (good/poor, CHCl3/CH3CN) demonstrated that squaraine dye 1 forms two novel H-type chiral supramolecular assemblies with opposite chirality at different good/poor solvent compositions. Model compound 2 formed J-type achiral assemblies under similar conditions. The supramolecular assembly of 1 observed at lower fractions of the poor solvent could be assigned to the thermodynamically stable form, while a kinetically controlled assembly is formed at higher fractions of the poor solvent. This assignment is evidenced by temperature- and concentration-dependent experiments. With increasing temperature, the chirality of the kinetically controlled aggregate was lost and, on cooling, the aggregate with the opposite chirality was formed. On further heating and cooling the aggregates thus formed resulted in no significant changes in chirality, that is they are thermodynamically stable. Similarly, at lower concentrations, the thermodynamically stable form exists, but at higher concentration aggregation was found to proceed with kinetic control. Based on these observations it can be assumed that formation of the kinetically controlled assembly might be largely dependent on the presence of the nonpolar cholesterol moiety as well as the amount of poor solvent present. However, under solvent-free conditions, structurally different aggregates were observed when drop cast from solutions containing monomer, whereas a left-handed CD signal corresponding to the thermodynamically controlled assemblies was observed from pre-aggregated solutions

A supramolecular ON-OFF-ON fluorescence assay for selective recognition of GTP

With the objective of developing small molecule based receptors for nucleosides and nucleotides, interactions of a cyclic donor-acceptor conjugate 1 with adenosine, AMP, ADP, CTP, UTP, ITP, ATP, and GTP have been investigated by absorption, steady-state, and time-resolved fluorescence, cyclic voltammetry (CV), NMR, and fluorescence indicator displacement techniques. Titration of 1 with the fluorescent indicator, 8-hydroxy-1,3,6-pyrene trisulfonate (HPTS), resulted in nearly complete fluorescence quenching of HPTS, along with 25% hypochromicity in its absorption spectrum. Benesi-Hildebrand analysis gave a 1:1 stoichiometry for the complex between the receptor 1 and HPTS with an association constant (Kass) of 4.66 × 104 M−1 in buffer. The driving force for such a complexation was evaluated to be the synergistic effects of π-stacking and electrostatic interactions inside the cavity as confirmed by the effect of ionic strength, temperature, and the negative results obtained with the model compound 2. Titration of the nonfluorescent complex [1.HPTS] with various nucleosides and nucleotides resulted in revival of fluorescence of the indicator, HPTS. It was observed that GTP induces maximum displacement of HPTS from the complex [1.HPTS] with an overall fluorescence enhancement of ca. 150-fold. The addition of adenosine, AMP, ADP, CTP, and UTP showed negligible changes, whereas ca. 45- and 50-fold enhancement was observed with ATP and ITP, respectively. The competitive displacement of the indicator by various analytes is found to be in the order GTP (buffer) ≈ GTP (biofluid) » ITP ≈ ATP > UTP > CTP ≈ ADP ≈ AMP ≈ Ade. By virtue of having a better π-electron cloud, GTP undergoes effective electronic, π-stacking, and electrostatic interactions inside the cavity and forms a stable complex with the receptor 1. The uniqueness of this assay is that it differentiates GTP from ATP and other nucleotides and signals the event through a visual "turn on" fluorescence mechanism in buffer as well as in biological fluids

Synthesis of novel quinaldine-based squaraine dyes: effect of substituents and role of electronic factors

Condensation of squaric acid with quinaldinium salts containing electron-donating substituents gave only the semisquaraines. However, with salts possessing electronegative and electron-withdrawing groups, the squaraine dyes were isolated in quantitative yields. The semisquaraines formed undergo condensation with highly nucleophilic salts yielding the unsymmetrical squaraine dyes. These results demonstrate the role of electronic factors and provide valuable information for the design of efficient squaraine-based sensitizers that can have potential applications in photodynamic therapy

Dual-mode semisquaraine-based sensor for selective detection of Hg<SUP>2+</SUP> in a micellar medium

A novel chemosensor based on semisquaraine dye (SSQ) for selective detection of Hg2+ is described. SSQ is obtained in quantitative yields from the reaction between squaric acid and 6-ethoxy-2-quinaldinium iodide. SSQ in combination with surfactant shows a dual chromogenic and fluorogenic response selectively toward Hg2+ as compared to Li+, Na+, K+, Ag+, Ca2+, Mg2+, Zn2+, Pb2+, Cd2+, Cu2+, and Fe3+ due to the soft acid nature and size of the mercuric ion

Aggregation Behavior of halogenated squaraine dyes in buffer, electrolytes, organized media, and DNA

Aggregation properties of bis(3,5-dibromo-2,4,6-trihydroxyphenyl)squaraine (1) and bis(3,5-diiodo-2,4,6-trihydroxyphenyl)squaraine (2) have been examined in buffer and in the presence of electrolytes, β-cyclodextrin, micelles and DNA. These dyes were found to form aggregates in buffer and methanol-water solutions that have absorption bands blue-shifted to those of the monomeric forms. The iodo derivative 2 forms aggregates at much lower concentrations (1.7 × 10<SUP>−6</SUP> M) compared to the bromo derivative 1 (2.35 × 10<SUP>−6</SUP> M) in 20% (vol/vol) methanol-buffer solution. Increase in methanol concentration in methanol-water solutions resulted in the disruption of the aggregates. The intermediate dimer in the monomer to aggregate conversion process can be detected under specified conditions. The entropy and the standard free energy for the dimer formation in the case of 1 are found to be -16.12 eu and 7.46 k cal mol<SUP>−1</SUP>, respectively. Addition of electrolytes (LiCl, NaCl, and KCl) and calf thymus DNA resulted in the enhancement of aggregate formation, whereas the monomer gets stabilized for several hours in the presence of microheterogeneous media such as β-cyclodextrin and cetyltrimethylammonium bromide. These results reveal that face-to-face stacking followed by hydrogen bonding interactions between the chromophoric units are the major driving force for the formation of sandwich (H-type) aggregates. These dyes exhibit favorable photophysical properties and can be applied into the tissues using carrier systems in which they do not form aggregates and hence can have potential use as sensitizers in photodynamic therapeutical applications