Origin of near-infrared absorption and large second hyperpolarizability in oxyallyl diradicaloids: a three-state model approach

Bis(benzofuranonyl)methanolate (BM4i4i) dye and croconate dyes (derivatives of oxyallyl molecules) in general are known to have intense transitions in the near-infrared (NIR) region, indicating small transition energies and large transition dipole moments. These molecules have been reported in the literature to have very large resonant third-order nonlinear optical (NLO) susceptibilities and molecular hyperpolarizabilities (gamma). In this work we investigate using density functional theory (DFT)/ab initio/symmetry adapted cluster-configuration interaction (SAC-CI) techniques the oxyallyl substructure and attribute the NIR transition and the NLO activity to this substructure, which is common in all these molecules. Using valence bond (VB) theory, an analysis of a three-state model of this substructure is carried out. It is seen that the mixture of an intermediate diradical character and some zwitterionic character in the molecule and a large coupling between these two VB resonance forms is responsible for large gamma values. This can be used as a design principle for increasing NLO activity in oxyallyl derivatives.     

Synthesis and Molecular Properties of Acceptor‐Substituted Squaraine Dyes

A broad series of more than 20 acceptor‐substituted squaraines was synthesized that feature different acceptor functionalities at the central squaraine four‐membered ring. The influence of these acceptor units on the reactivity of semisquaraine precursors and stability of the respective squaraines were explored. Thereby the dicyanovinyl group was found to be the most versatile acceptor group that enabled various modifications at the donor moiety of the squaraine scaffold, leading to an extended series of dicyanovinyl‐functionalized squaraines. The variation of donor units afforded a set of NIR fluorophores that cover a wavelength region from the visible at about 650 nm far into the NIR up to 920 nm with fluorescence quantum yields between 0.93 and 0.11 and outstanding optical brightness. This excellent optical property is related to a rigid molecular scaffold that is fixed in an all‐cis configuration by the additional dicyanovinyl acceptor unit. The change of the molecular symmetry from C_2h to C_2v upon functionalization of the squaraine core with dicyanovinyl acceptor group has been confirmed in solution by electro‐optical absorption (EOA) spectroscopy, revealing permanent ground‐state dipole moments μ_g in the range between 4.3 and 6.4 D. These dipole moments direct an antiparallel packing of the molecules in the solid state according to single‐crystal X‐ray analyses achieved for four dicyanovinyl‐functionalized squaraines. The structural properties, the EOA results, as well as the band shapes of the optical spectra indicate that these polymethine dyes are cyanine‐type chromophores. It is worth noting that the orientation of the dipole moment vectors is orthogonal to the orientation of the transition dipole moment vectors, which is an uncommon but characteristic feature of this rather novel class of polymethine dyes. With regard to applications of these dyes in organic solar cells, their redox properties were also studied by cyclic voltammetry.     

Near-infrared absorption in symmetric squarylium and croconate dyes: a comparative study using symmetry-adapted cluster-configuration interaction methods

Symmetric croconate (CR) and squarylium dyes (SQ) are well-known near-infrared (NIR) dyes and, in general, are considered to be donor-acceptor-donor type molecules. It is established in the literature that CR dyes absorb in a longer wavelength region than the corresponding SQ dyes. This has been attributed to the CR ring being a better acceptor than the SQ ring. Thus increasing the donor capacity should lead to a bathochromic shift in both SQ and CR. On the other hand, some experiments reported in the literature have revealed that increasing the conjugation in the donor part of the SQ molecule leads first to red shift, which upon a further increase of the conjugation changes to a blue shift. Hence, to understand the role of the central ring and the substitutions in the absorption of these dyes, we carried out high-level symmetry-adapted cluster-configuration interaction (SAC-CI) calculations of some substituted SQ and CR dyes and compare the absorption energy with the existing experimental data. We found that there is very good agreement. We also carried out SAC-CI calculations of some smaller model molecules, which contain the main oxyallyl substructure. We varied the geometry (angle) of the oxyallyl subgroup and the substitution in these model molecules to establish a correlation with the bathochromic shift. We found that the charge transfer is very small and does not play the key role in the red shift, but on the other hand, the perturbation of the HOMO-LUMO gap (HLG) from both the geometry and substitution seems to be responsible for this shift. We suggest as a design principle that increasing the donor capacity of the groups may not help in the red shift, but introducing groups which perturb the HLG and decrease it without changing the MO character should lead to a larger bathochromic shift.     

An ab initio study of the absorption spectra of indirubin, isoindigo, and related derivatives

The UV/visible spectra of a series of indirubin, isoindigo, and other indigo/thioindigo related dyes have been evaluated in various solvent environments by using the time-dependent density functional theory in conjunction with the polarizable continuum model. Even for molecules of the same family, significant differences in the excitation processes have been noted. Two hybrid functionals have been selected: B3LYP and PBE0. For a set of the 50 selected molecular cases, both functionals provide accurate lambda(max), with mean absolute deviations limited to 0.1 eV. Actually, isoindigo is the main challenging series, with systematically underestimated excitation energies, due to the different nature of the excitation process. In most cases, we found that PBE0 is more efficient in reproducing the experimental values than B3LYP for sulfur-containing dyes not featuring internal hydrogen bonds, the reverse assertion being also true. In addition, the spectra of a series of unknown dyes have been predicted.     

Rational Design of Fluorescent Bioimaging Probes by Controlling the Aggregation Behavior of Squaraines: A Special Effect of Ionic Liquid Pendants

We herein present an effective strategy to create water‐soluble fluorescent bioimaging dyes by introducing the imidazolium‐based ionic liquid (IL) pendants into a fluorescent skeleton. A new type of water‐soluble imidazolium‐anchored squaraine dye was synthesized accordingly. The relationship between the aggregate of squaraines and their fluorescent cell imaging application was elucidated in detail. Firstly, the aggregation behavior of squaraines in water solutions could be suppressed by varying the alkyl chain attached to the imidazolium unit. Secondly, the capability of cellular uptake and staining of dyes was also dramatically enhanced upon increasing the length of the paraffinic chain. These squaraine dyes displayed an excellent photostability that could permit real‐time fluorescence bioimaging experiments to be monitored over a long time period with constant sample irradiation. Additionally, we designed for the first time an Fe^II‐ion probe on the basis of an attack of the hydroxyl radical to the four‐membered ring of squaraine. The results demonstrated that the imidazolium‐anchored squaraines could perform “naked‐eye” detection of the Fe²⁺ ion over a wide range of other interfering metals in aqueous media. More surprisingly, this process showed a fluorescence “turn‐off” and “‐on” response through the regeneration of squaraines in cells.     

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.     

Squaraine Dyes as Fluorescent Turn-on Probes for Mucins: A Step Toward Selectivity†

Mucins are a family of long polymeric glycoproteins which can be overexpressed in several types of cancers, and over recent years, great attention was addressed to identify mucins as an important biomarker of adverse prognosis. Fluorometric detection mediated by fluorescent probes could represent a winning strategy in the early diagnosis of different pathologies. Among promising biological fluorescent probes, squaraines are gaining particular attention, thanks to their sharp and intense absorption and emission in the NIR region. In this contribution, three squaraine dyes bearing different substituents and with different lipophilicity have been investigated for their ability to detect mucin. The turn-on response upon the addition of mucin has been investigated by means of absorbance and fluorescence spectroscopy. After a preliminary screening, the squaraine (S6) bearing bromine as a substituent and C4 aliphatic chains showed the highest fluorescence turn-on and highest affinity for mucin than albumin. To further highlight the selectivity of S6 for mucin, the fluorescence response has been evaluated in the presence of serum and site-specific proteins different than albumin. Absorption spectroscopy was used to characterize the binding mechanism of squaraine to mucin.     

Microreview: Pyrrol‐3‐yl squaraines (including indol‐3‐yl squaraines)

Pyrrol‐3‐yl squaraine dyes are prepared by the condensation of 3,4‐dihydroxycyclobut‐3‐ene‐1,2‐dione with two‐molar equivalence of a 2,5‐disubstituted pyrrole possessing a free β‐position, or substituted indoles with a similarly free β‐position. From the first reported syntheses of two indol‐3‐yl squaraines in 1966, numerous pyrrol‐3‐yl squaraines (including indol‐3‐yl squaraines) have been reported in both the scientific and patent literatures. This microreview highlights the synthesis, history, spectroscopy, and applications of pyrrol‐3‐yl squaraines from their first preparation to the present date.     

Squaraine Dyes: Interaction with Bovine Serum Albumin to Investigate Supramolecular Adducts with Aggregation‐Induced Emission (AIE) Properties

Bovine serum albumin (BSA)–squaraine supramolecular adducts with aggregation‐induced emission (AIE) properties were prepared and characterized by spectroscopic methods. While squaraine dyes showed a very low fluorescence quantum yield in water, a great enhancement in the fluorescence of the aggregated BSA adducts was achieved due to the abnormal aggregation‐induced emission properties of squaraines. The adducts formation was studied from a kinetic point of view showing unexpected structure–properties relationships.     

Solvent-induced organization of squaraine dyes in solution capillary layers and adsorbed films

Unusual behavior of indolenine and hydroxyphenyl squaraines has been observed in solution capillary layers and adsorbed films. The confined solutions showed anomalous aggregation of squaraine molecules in contrast to their monomer behavior in the bulk solutions of the same concentration, along with formation of a macroscopic cell-like structure in the confined solution layer, with the diameter of cells being 3-5 microm. The aggregate structure, as observed through electronic absorption spectra, was strongly dependent on the chemical structure of squaraine used and solvent used, and it also was different from squaraine aggregates observed in aqueous solutions and films prepared by vacuum evaporation. It has been found that indolenine squaraine is capable of forming H-aggregates in confined dimethylformamide solutions and hydroxyphenyl squaraine is capable of forming J-aggregates in confined dimethylformamide solutions and adsorbed films. The results were compared with pseudoisocyanine, which forms J-aggregates in aqueous bulk solutions readily; however, no J-aggregates have been found in their capillary layers. The interplay of dye-dye, dye-surface, and dye-solvent interactions resulting in the above effects is discussed.     

Squaraine dyes for photodynamic therapy: mechanism of cytotoxicity and DNA damage induced by halogenated squaraine dyes plus light (>600 nm)

Halogenated squaraine dyes 1 and 2 possess favorable photophysical and in vitro photobiological properties that make these new class of molecules interesting for photodynamic therapeutic applications. For a better understanding of the mechanism of their photobiological activity, we have analyzed the DNA damage and the cytotoxicity induced by these photosensitizers in mammalian cells and cell-free systems in the presence and absence of various additives and scavengers. Both photoactivated squaraines were found to be similar efficient in inducing single-strand breaks (SSB) in cell-free DNA when compared with the cellular DNA. Superoxide dismutase and catalase did not show any influence. However, the presence of tert-butanol and glutathione inhibited the formation of the DNA SSB, indicating an indirect (possibly squaraine radical mediated) mechanism under cell-free conditions. Replacing H2O in the buffer by D2O resulted in a five- to six-fold increase in the number of the SSB in cell-free DNA and a significant enhancement of the photocytotoxicity in mouse lymphoma cells. The results demonstrate that singlet oxygen is the major reactive species under cell-free and cellular conditions and confirm that squaraine-based sensitizers 1 and 2 can have potential applications in photodynamic therapy.     

A High-Affinity “Synthavidin” Receptor for Squaraine Dyes

Strong-binding host–guest pairings in aqueous media have potential as “supramolecular glues” in biomedical techniques, complementing the widely-used (strept)avidin-biotin combination. We have previously found that squaraine dyes are bound very strongly by tetralactam macrocycles possessing anthracenyl units as cavity walls. Here we show that replacing the anthracenes with pentacyclic 5,7,12,14-tetrahydro-5,7,12,14-tetraoxapentacene (TOP) units generates receptors which bind squaraines with increased affinities (around K_a=10¹⁰ m ⁻¹) and improved selectivities. Binding can be followed through changes to squaraine fluorescence and absorbance. The TOP units are easy to prepare and potentially variable, while the TOP-based receptor shows improved photostability, both in itself and in complex with squaraines. The results suggest that this system could prove valuable in the further development of practical “synthavidin” chemistry.     

DFT study on singlet diradical character of zethrenes

The diradical character of zethrenes was investigated using a symmetry-broken UB3LYP/6-311G(d,p) method. The number of hexagons in the investigated molecules ranges from 6 to 12. It was found that all zethrenes are singlet diradicals, whose diradical character increases with the increasing size of the molecules. A singlet diradical structure provides a possibility for an electron pair to occupy different parts of space, and allows for achieving aromatic stabilization. It can be predicted, on the basis of the singlet-triplet values, that even higher zethrenes will be singlet, but not triplet molecules.     

Isomeric Squaraine‐Based [2]Pseudorotaxanes and [2]Rotaxanes: Synthesis,Optical Properties,and Their Tubular Structures in the Solid State

On the basis of formation of [2]pseudorotaxane complexes between triptycene‐derived tetralactam macrocycles 1 a and 1 b and squaraine dyes, construction of squaraine‐based [2]rotaxanes through clipping reactions were studied in detail. As a result, when two symmetrical squaraines 2 d and 2 e were utilized as templates, two pairs of isomeric [2]rotaxanes 3 a – b and 4 a – b as diastereomers were obtained, owing to the two possible linking modes of triptycene derivatives. It was also found, interestingly, that when a nonsymmetrical dye 2 g was involved, there existed simultaneously three isomers of [2]rotaxanes in one reaction due to the different directions of the guest threading. The ¹H NMR and 2D NOESY NMR spectra were used to distinguish the isomers, and the yield of [2]rotaxane 5 a with the benzyl group in the wider rim of the host 1 a was found to be higher than that of another isomer 5 b with an opposite direction of the guest, which indicated the partial selection of the threading direction. The X‐ray structures of 3 b and 4 a showed that, except for the standard hydrogen bonds between the amide protons of the hosts and the carbonyl oxygen atoms of the guests, multiple π???π stacking and C? H???π interactions between triptycene subunits and aromatic rings of the guests also participated in the complexation. Crystallographic studies also revealed that the [2]rotaxane molecules 3 b and 4 a further self‐assembled into tubular structures in the solid state with the squaraine dyes inside the channels. In the case of 4 a , all the nonsymmetrical macrocyclic molecules pointed in one direction, which suggests the formation of oriented tubular structures. Moreover, it was also found that the squaraines encapsulated in the triptycene‐derived macrocycles were protected from chemical attack, and subsequently have potential applications in imaging probes and other biomedical areas.     

Squaraines as reporter units: insights into their photophysics, protonation, and metal-ion coordination behaviour

The synthesis, photophysical properties, protonation, and metal-ion coordination features of a family of nine aniline-based symmetrical squaraine derivatives are reported. The squaraine scaffold displays very attractive photophysical properties for a signalling unit. These dyes show absorption and weakly Stokes-shifted, mirror-image-shaped emission bands in the visible spectral range and there are no hints of multiple emission bands. The mono-exponential fluorescence decay kinetics observed for all the derivatives indicate that only one excited state is involved in the emission. These data stress the interpretation that squaraines can be regarded as polymethine-type dyes. From a coordination chemistry point of view, the squaraines possess four potential binding sites; that is, two nitrogen atoms from the anilino groups and two oxygen atoms from the central C(4)O(2) four-membered ring. These coordination sites are part of a cross-conjugated pi-system and coordination events with protons or certain metal ions affect the electronic properties of the delocalised pi-system dramatically, resulting in a rich modulation of the colour of the squaraines. The absorption band at around 640 nm is blue-shifted when coordination at the anilino nitrogen atoms occurs, whereas coordination to the C(2)O(4) oxygen atoms results in the development of red-shifted bands. Addition of more than one equivalent of protons or metal cations could additionally entail mixed N,O- or N,N-coordinated complexes, manifested in the development of a broad band at 480 nm or complete bleaching in the visible range, respectively. Analysis of the spectrophotometric titration data with HYPERQUAD yielded the macroscopic and microscopic stability constants of the complexes. Theoretical modelling of the various protonated species by molecular mechanics methods and consideration of some of the title dyes within the framework of molecular chemosensing and molecular-scale "logic gates" complement this contribution.     

Cycloheptatrienyl oxyallyl. An observable oxyallyl?

Density functional calculations have been carried out for cycloproylidene-, cyclopentylidene-, and tropyllideneallene oxides (7-9) and the reaction pathway for their conversion to the corresponding oxyallyls (10-12) and cyclopropanones (13-15) in order to probe the electronic structure of the intermediate oxyallyls. All three oxyallyls were found to be stabilized with respect to their allene oxides in comparison to the unsubstituted allene oxide and oxyallyl. For 7 and 9 the stabilization can be attributed to the zwitterionic character of the oxyallyls, while for 8 the stabilization can be attributed to its diradical character. This suggests that oxyallyl is capable of "adapting" to its local environment. Calculations predict that oxyallyl 12 should be an observable intermediate in the absence of nucleophiles, since it is calculated to be of lower energy than either the allene oxide 9 or the cyclopropanone 15.     

Squaraine dyes as efficient coupling bridges between triarylamine redox centres

Various indolenine squarylium dyes with additional electron-donating amine redox centres have been synthesised and their redox chemistry has been studied. A combination of cyclic voltammetry, spectro-electrochemistry and DFT calculations has been used to characterise the electronic structure of the mono-, di- and, in one case, trications. All monocations still retain the cyanine-like, delocalised character due to the relatively low redox potential of the squaraine bridge and are therefore compounds of Robin-Day class III. Thus we extended previous studies on organic mixed-valence systems by using the indolenine squaraine moiety as very electron-rich bridge between two electron-donating amine redox centres to provoke a strong coupling between the additional redox centres. We synthesised TA3, which has an N-N distance of 26 bonds between the triarylamine redox centres and is to our knowledge the longest bis(triarylamine) radical cation that is completely delocalised. We furthermore show that altering the symmetry of a squaraine dye by substitution of a squaric ring oxygen atom by a dicyanomethylene group has a direct impact on the optical properties of the monocations. In case of the dications, it turned out that the energetically most stable state of dianisylamine-substituted squaraines is an anti-ferromagnetically coupled open-shell singlet state.     

1H NMR spectral evidence for a specific host-guest complexation induced charge localization in squaraine dyes

[reaction: see text]. Experimental support is provided for the charge localization in squaraines, a class of fundamentally and technologically important organic dyes, by (1)H NMR analysis through a host-guest complexation approach. Specific binding of Ca(2+) ions to the squaraine 2 with a podand sidearm resulted in a charge-localized structure 2a with dramatic shifts and resolution of the proton signals when compared to those of 2.