Cartilage‐Specific Near‐Infrared Fluorophores for Biomedical Imaging

A novel class of near‐infrared fluorescent contrast agents was developed. These agents target cartilage with high specificity and this property is inherent to the chemical structure of the fluorophore. After a single low‐dose intravenous injection and a clearance time of approximately 4 h, these agents bind to all three major types of cartilage (hyaline, elastic, and fibrocartilage) and perform equally well across species. Analysis of the chemical structure similarities revealed a potential pharmacophore for cartilage targeting. Our results lay the foundation for future improvements in tissue engineering, joint surgery, and cartilage‐specific drug development.     

Using End Groups to Tune the Linear and Nonlinear Optical Properties of Bis(dioxaborine)‐Terminated Polymethine Dyes

Six anionic pentamethine dyes with different 2,2‐difluoro‐4‐aryl‐1,3,2(2 H)‐dioxaborin‐6‐yl termini were synthesized and isolated as tetra‐n‐octylammonium salts with a variety of aryl groups appended to increase conjugation beyond the dioxaborine termini. The increased conjugation was expected to decrease the energy of the lowest‐lying excited state, and increase the transition dipole moment linking this state to the ground state, which would be anticipated to result in an increase in the real part of the third‐order polarizability, Re(γ). UV/Vis‐NIR absorption spectroscopy indicates that the absorption maxima in DMSO vary from 691 to 761 nm, with the longest wavelength transitions observed for a derivative where the aryl group is 4‐nitrophenyl. Closed‐aperture Z‐scan measurements at 1.3 μm in DMSO indicate that Re(γ) varies from ?2.9×10^?33 to ?5.4×10^?33 esu in these systems. The largest magnitude of Re(γ) was observed for a dye with E‐4‐styrylphenyl aryl groups. This result can be rationalized using a two‐state expression which relates Re(γ) to the energy and transition dipole moment of the transition from the ground state to the lowest‐lying excited state. A nonamethine analogue of this compound was also synthesized and exhibits a slightly larger Re(γ) with respect to a previously reported bis(dioxaborine)‐terminated nonamethine. The extension of conjugation beyond the dioxaborine termini seems to result in an overall increase in Re(γ). However, the effects are smaller than those found by increasing conjugation in the polymethine bridge due to reduced participation of terminal groups in the HOMO.     

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.     

On the Signalling Pathways and CuII‐Mediated Anion Indication of N‐meso‐Substituted Heptamethine Cyanine Dyes

Join or attack : meso‐Cyclam‐substituted heptamethine cyanine dye 1 responds very differently to the presence of metal ions and protons. Whereas the former are embraced in a host–guest complex, the latter attack the cyanine π system (see picture). In the presence of Cu^II, 1 selectively forms near‐infrared absorbing aggregates in buffered solution that allow the determination of citrate by using colourimetry.

     

BOIMPYs: Rapid Access to a Family of Red‐Emissive Fluorophores and NIR Dyes

A fundamental, highly fluorescent, and easily accessible scaffold derived from the BODIPY core is reported. The use of benzimidazole as a bridging ligand at the meso position enables the binding of two BF₂ units to provide sufficient rigidity and enhanced electron‐withdrawing strength. Absorption and emission events thus take place in the red (λ≈600 nm); the fluorescence quantum yields can reach unity (0.96) and show little dependence on solvent polarity. The synthetic route was shortened to two steps starting from commercially available precursors while the preparation is modular and tolerates various pyrrole and benzimidazole moieties. Fluoride replacement by propynyl groups, various halogenations, as well as Knoevenagel‐type condensations were applied to extend the versatility of these new photostable fluorophores, which we termed BOIMPYs.     

The Nature of Organically Modified Ceramics as Reflected by Photophysics of Trapped HITC

Phase resolved fluorescence spectroscopy (PRFS) is used to analyze fluorescence emission decay kinetics of 1,1,3,3,3,3 -hexamethylindotricarbocyanine iodide (HITC) doped in different Organically Modified Ceramics (Ormocers), yielding information about the identity of the different environment surroundings of the organic dye. We report the first results on PRFS regarding to establish a relation between the HITC photophysics and the characteristics of the Ormocer surface. Lifetimes resolution and fractional contribution of different HITC species to the total fluorescence emission were reported. An increase in the HITC chemical stability was found for doped Ormocers in comparison to inorganic gel-glasses. Scanning and transmission electron microscopy (SEM) images of the Ormocers were showed.     

Pyrrolopyrrole Cyanine Dyes: A New Class of Near‐Infrared Dyes and Fluorophores

NIRer there : Pyrrolopyrrole cyanine (PPCys) dyes, a new class of near‐infrared (NIR) fluorophores, are obtained by condensation of heteroarylacetonitrile and diketopyrrolopyrrole compounds (see picture). Complexation with BF₂ or BPh₂ yields strongly fluorescent, photostable NIR dyes that show high absorption cross‐sections and fluorescence quantum yields. Furthermore, alteration of the heterocycle can tune the main absorption between λ = 684 and 864 nm.

     

Widely Electronically Tunable 2,6-Disubstituted Dithieno[1,4]thiazines—Electron-Rich Fluorophores Up to Intense NIR Emission

2,6-Difunctionalized dithieno[1,4]thiazines were efficiently synthesized by (pseudo)five- or (pseudo)three-component one-pot processes based on lithiation-electrophilic trapping sequences. As supported by structure–property relationships, the thiophene anellation mode predominantly controls the photophysical and electrochemical properties and the electronic structures (as obtained by DFT calculations). From molecular geometries and redox potentials to fluorescence quantum yields in solution, the interaction of the dithieno[1,4]thiazine-core with the substituents causes striking differences within the series of regioisomers. Most interestingly, strong acceptors introduced in anti–anti dithieno[1,4]thiazines nearly induce a planarization of the ground-state geometry and a highly intense NIR fluorescence (Φ_F=0.52), whereas an equally substituted syn–syn dithieno[1,4]thiazine exhibits a much stronger folded molecular structure and fluoresces poorly (Φ_F=0.01). In essence, electrochemical and photophysical properties of dithieno[1,4]thiazines can be tuned widely and outscore the compared phenothiazine with cathodically shifted oxidation potentials and redshifted and more intense absorption bands.