Aza-BODIPY nanomicelles as versatile agents for the in vitro and in vivo singlet oxygen-triggered apoptosis of human breast cancer cells.

Herein, we synthesised four aza-BODIPY dyes (1-4) with the singlet oxygen generation quantum yield values of ca. 65-85%. Furthermore, we formulated a nanomedicine by encapsulating these dyes into an amphiphilic micelle, DSPE. The spherical nanomicelles formed were characterized using photophysical and morphological analyses, and their in vitro and in vivo photodynamic efficacies were investigated. One of the conjugates, DSPE-1, showed the lowest IC50 value of 2 µM against a human breast cancer cell line (MDA MB 231). The mechanism of photodynamic activity has been evaluated by employing different biophysical and morphological assays, which confirmed apoptotic cell death (ca. 80-90%) predominantly through the involvement of reactive oxygen species. Interestingly, we observed that 2 mg kg-1DSPE-1 induced enhanced apoptosis and efficient inhibition of the growth of breast tumor xenografts in NOD/SCID mice models. Herein, we demonstrated the application of aza-BODIPY nanomicelles in photodynamic therapy for the first time, and our results revealed that the DSPE-BODIPY nanomicelles enhanced the cellular uptake as well as the photodynamic activity, thereby demonstrating the use of these nanomicelles as efficient sensitizers in biological applications.

Fluorescence quenching by intercalation of a pyrene group tethered to an N4-modified cytosine in duplex DNA.

A series of duplex DNA oligomers was prepared that contain a pyrene chromophore linked by a trimethylene chain (-(CH2 )3 -) to N(4) of a cytosine. The pyrene group stabilizes the DNA as evidenced by an increase in melting temperature. The absorption spectrum of the linked pyrene chromophore shows a temperature-dependent shift and there is also a strong induced circular dichroism spectrum attributed to the pyrene group. The fluorescence of the pyrene chromophore is strongly quenched at room temperature by linkage to the DNA, but it increases above the melting temperature. We attribute these observations to intramolecular intercalation of the pyrene group at a base pair adjacent to its linkage site at cytosine.

Aza-BODIPY derivatives: enhanced quantum yields of triplet excited states and the generation of singlet oxygen and their role as facile sustainable photooxygenation catalysts.

A new series of aza-BODIPY derivatives (4 a-4 c, 5 a,c, and 6 b,c) were synthesized and their excited-state properties, such as their triplet excited state and the yield of singlet-oxygen generation, were tuned by substituting with heavy atoms, such as bromine and iodine. The effect of substitution has been studied in detail by varying the position of halogenation. The core-substituted dyes showed high yields of the triplet excited state and high efficiencies of singlet-oxygen generation when compared to the peripheral-substituted systems. The dye 6 c, which was substituted with six iodine atoms on the core and peripheral phenyl ring, showed the highest quantum yields of the triplet excited state (Φ(T) =0.86) and of the efficiency of singlet-oxygen generation (Φ(Δ) =0.80). Interestingly, these dyes were highly efficient as photooxygenation catalysts under artificial light, as well as under normal sunlight conditions. The uniqueness of these aza-BODIPY systems is that they are stable under irradiation conditions, possess strong red-light absorption (620-680 nm), exhibit high yields of singlet-oxygen generation, and act as efficient and sustainable catalysts for photooxygenation reactions.

Squaraine dyes in PDT: from basic design to in vivo demonstration.

The design and development of novel squaraine dyes as sensitisers for photodynamic therapy (PDT) applications has grown tremendously in the last decade from the time when a squaraine dye was proposed to be a potential candidate, to-date when the use of such dyes have been demonstrated in animal models for skin cancer. This perspective article highlights the basic design, tuning of absorption, triplet excited state and two-photon absorption properties and recent developments of the squaraines as PDT sensitisers.

Novel semisquaraine regioisomers: isolation, divergent chemical reactivity and photophysical properties.

A zwitterionic semisquaraine 1,3-regioisomer which exhibits distinct photophysical properties and chemical reactivity was isolated. Uniquely, this isomer has been identified as the reactive intermediate in the squaraine dye formation reaction rather than the neutral 1,2-isomer and opens up new avenues for the synthesis of novel dyes for optoelectronic applications.

ß-Cyclodextrin as a photosensitizer carrier: effect on photophysical properties and chemical reactivity of squaraine dyes.

With the objective of understanding the utility of ß-cyclodextrin (ß-CD) as a carrier system, we have investigated its interactions with a few near-infrared absorbing squaraine dyes (i.e., 1a,b and 2a,b) through absorption and steady-state and time-resolved fluorescence techniques. The addition of ß-CD to the phloroglucinol dyes 1a,b resulted in a significant bathochromic shift in absorption, together with a ca. 1.5-2.5-fold enhancement in fluorescence intensity, whereas for the aniline-based dyes 2a,b, a hypsochromic shift in the absorption and a ca. 5-12-fold fluorescence enhancement were observed in a 10% (v/v) ethanol/water mixture. Benesi-Hildebrand analysis showed that both the dyes 1a,b and 2a,b form 2:1 stoichiometric complexes with ß-CD. The complex formation was confirmed by competitive binding analysis employing adamantyl-1-carboxylic acid (ACA) and adamantyl-1-ammonium chloride (ADAC). The displacement of the dyes 1a,b and 2a,b from the [dye-ß-CD] complex by ADAC and ACA unambiguously establishes the encapsulation of these dyes in the hydrophobic nanocavity of ß-CD. Uniquely, the formation of the inclusion complexes with ß-CD provides unusual protection from nucleophilic attack by aminothiols such as cysteine and glutathione for dyes 1a,b, whereas negligible protection was observed for dyes 2a,b. These results demonstrate the substituent-dependent encapsulation of potentially useful squaraine dyes in ß-CD, thereby indicating its potential as a carrier system for the squaraine dyes 1a,b useful in photodynamic therapy.

Tuning photosensitized singlet oxygen generation efficiency of novel aza-BODIPY dyes.

Novel aza-BODIPY derivatives substituted with heavy atoms such as bromine and iodine were synthesized, and their triplet and singlet oxygen generation efficiencies have been investigated. These derivatives showed absorption in the NIR region with high molar extinction coefficients. The dye substituted with four iodine atoms showed yields of Φ(T) = 0.78 and Φ((1)O(2)) = 0.70, which are the highest values so far obtained for the aza-BODIPY derivatives.

Functional cyclophanes: promising hosts for optical biomolecular recognition.

Cyclophanes possess a defined cavity size and are efficient in encapsulating and stabilising guest molecules inside the cavity through various non-covalent interactions. This unique property of the cyclophanes has been widely exploited for the development of selective probes for a variety of guest molecules. The present tutorial review highlights the use of various interesting functionalised cyclophane architectures for the sensitive and selective optical recognition of important biomolecules.

Infrared absorbing croconaine dyes: synthesis and metal ion binding properties.

Quinaldine-based croconaine dyes synthesized by the condensation reaction between croconic acid and the respective quinaldinium salts are described. These dyes exhibit absorption maximum in the infrared region (840-870 nm) with high molar extinction coefficients (1-5 x 10(5) M(-1) cm(-1)) and have very low fluorescence quantum yields. Upon binding to divalent metal ions, these dyes were found to form complexes with a 2:1 stoichiometry having high association constants of the order of 10(11)-10(14) M(-2), while the monovalent metal ions showed negligible affinity. The binding of the croconaine dye 3d with divalent metal ions especially Zn(2+), Pb(2+), and Cd(2+) led to significant chelation-enhanced fluorescence emission. The broadening of the aromatic signals, vinylic and N-methyl protons and the negligible changes at the aliphatic region of the dye 3d in the (1)H NMR spectrum in the presence of Zn(2+), indicate that the binding occurs at the carbonyl groups of the croconyl ring. The shift in the croconyl carbonyl stretching frequency in the [3d-Zn(2+)] complex analyzed through FT-IR analysis further confirms the involvement of two electron-rich carbonyl groups of the croconyl moiety in the complexation. These results demonstrate that the binding of the divalent metal ions at the carbonyl oxygens of these infrared absorbing dyes can be favorably utilized for the development of potential sensors for the detection of metal ions and further can be exploited as sensitizers for photodynamic therapeutic applications.

Dual-mode semisquaraine-based sensor for selective detection of Hg2+ in a micellar medium.

[reaction: see text] 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.

Synthesis of new cholesterol- and sugar-anchored squaraine dyes: further evidence of how electronic factors influence dye formation.

[reaction: see text] Synthesis of new quinaldine-based squaraine dyes linked to cellular recognition elements that exhibit near-infrared absorption (>740 nm) are described. Both product analysis and theoretical calculations substantiate the interesting electronic effects of various substituents in the dye formation reaction. These results are useful in the synthesis of symmetrical and unsymmetrical squaraine dyes that can have potential biological and photodynamic therapeutical applications.