Modulating the Optical Properties of BODIPY Dyes by Noncovalent Dimerization within a Flexible Coordination Cage.

Aggregation of organic molecules can drastically affect their physicochemical properties. For instance, the optical properties of BODIPY dyes are inherently related to the degree of aggregation and the mutual orientation of BODIPY units within these aggregates. Whereas the noncovalent aggregation of various BODIPY dyes has been studied in diverse media, the ill-defined nature of these aggregates has made it difficult to elucidate the structure-property relationships. Here, we studied the encapsulation of three structurally simple BODIPY derivatives within the hydrophobic cavity of a water-soluble, flexible PdII6L4 coordination cage. The cavity size allowed for the selective encapsulation of two dye molecules, irrespective of the substitution pattern on the BODIPY core. Working with a model, a pentamethyl-substituted derivative, we found that the mutual orientation of two BODIPY units in the cage's cavity was remarkably similar to that in the crystalline state of the free dye, allowing us to isolate and characterize the smallest possible noncovalent H-type BODIPY aggregate, namely, an H-dimer. Interestingly, a CF3-substituted BODIPY, known for forming J-type aggregates, was also encapsulated as an H-dimer. Taking advantage of the dynamic nature of encapsulation, we developed a system in which reversible switching between H- and J-aggregates can be induced for multiple cycles simply by addition and subsequent destruction of the cage. We expect that the ability to rapidly and reversibly manipulate the optical properties of supramolecular inclusion complexes in aqueous media will open up avenues for developing detection systems that operate within biological environments.

Design and Evaluation of a Boron Dipyrrin Electrophore for Redox Flow Batteries.

A boron dipyrrin (BODIPY) dye was designed as a molecular single-component electrophore for redox flow batteries. All positions of the BODIPY core were assessed on the basis of literature data, in particular cyclic voltammetry and density functional calculations, and a minimum required substitution pattern was designed to provide solubility, aggregation, radical cation and anion stabilities, a large potential window, and synthetic accessibility. In-depth electrochemical and physical studies of this electrophore revealed suitable cathodic behavior and stability of the radical anion but rapid anodic decomposition of the radical cation. The three products that formed under the conditions of controlled oxidative electrolysis were isolated, and their structures were determined by spectroscopy and comparison with a synthetic model compound. From these structures, a benzylic radical reactivity, initiated by one-electron oxidation, was concluded to play the major role in this unexpected decomposition.

Controlling the lifetimes of dynamic nanoparticle aggregates by spiropyran functionalization.

Novel light-responsive nanoparticles were synthesized by decorating the surfaces of gold and silver nanoparticles with a nitrospiropyran molecular photoswitch. Upon exposure to UV light in nonpolar solvents, these nanoparticles self-assembled to afford spherical aggregates, which disassembled rapidly when the UV stimulus was turned off. The sizes of these aggregates depended on the nanoparticle concentration, and their lifetimes could be controlled by adjusting the surface concentration of nitrospiropyran on the nanoparticles. The conformational flexibility of nitrospiropyran, which was altered by modifying the structure of the background ligand, had a profound impact on the self-assembly process. By coating the nanoparticles with a spiropyran lacking the nitro group, a conceptually different self-assembly system, relying on a reversible proton transfer, was realized. The resulting particles spontaneously (in the dark) assembled into aggregates that could be readily disassembled upon exposure to blue light.

Circularly Polarized Luminescence from Axially Chiral BODIPY DYEmers: An Experimental and Computational Study.

With our new home-built circularly polarized luminescence (CPL) instrument, we measured fluorescence and CPL spectra of the enantiomeric pairs of two quasi-isomeric BODIPY DYEmers 1 and 2, endowed with axial chirality. The electronic circular dichroism (ECD) and CPL spectra of these atropisomeric dimers are dominated by the exciton coupling between the main π-π* transitions (550-560 nm) of the two BODIPY rings. Compound 1 has strong ECD and CPL spectra (glum =4×10-3 ) well reproduced by TD-DFT and SCS-CC2 (spin-component scaled second-order approximate coupled-cluster) calculations using DFT-optimized ground- and excited-state structures. Compound 2 has weaker ECD and CPL spectra (glum =4×10-4 ), partly due to the mutual cancellation of electric-electric and electric-magnetic exciton couplings, and partly to its conformational freedom. This compound is computationally very challenging. Starting from the optimized excited-state geometries, we predicted the wrong sign for the CPL band of 2 using TD-DFT with the most recommended hybrid and range-separated functionals, whereas SCS-CC2 or a DFT functional with full exact exchange provided the correct sign.

Acidic Condensation of BODIPYs with Aldehydes: A Quick and Versatile Route to Alkenyl-BODIPYs and C(sp(3) )-Connected DYEmers.

The condensation of aldehydes with BODIPY (boron dipyrrin) luminophores was investigated. Formaldehyde can be used to connect two BODIPYs at each of the three pyrrolic C positions (α-, ß-, and ß'-positions) in a quick and highly selective manner, yielding new DYEmers (di- and oligomeric BODIPY derivatives) with varied photophysical properties. Benzaldehydes form DYEmers only at the ß- and the ß'-positions. For aliphatic aldehydes the DYEmer formation competes with the elimination of water from a proposed alcohol intermediate, leading to the formation of α- and ß-alkenyl-BODIPYs. 2-Phenylacetaldehyde and similar precursors exclusively yield elimination products. These acid-mediated transformations are valuable alternatives to the well-established, base-promoted Knoevenagel condensation protocol that is typically employed in the preparation of BODIPYs with near infrared (NIR)-shifted absorptions.

Reversible Photoisomerization of Spiropyran on the Surfaces of Au25 Nanoclusters.

Au25 nanoclusters functionalized with a spiropyran molecular switch are synthesized via a ligand-exchange reaction at low temperature. The resulting nanoclusters are characterized by optical and NMR spectroscopies as well as by mass spectrometry. Spiropyran bound to nanoclusters isomerizes in a reversible fashion when exposed to UV and visible light, and its properties are similar to those of free spiropyran molecules in solution. The reversible photoisomerization entails the modulation of fluorescence as well as the light-controlled self-assembly of nanoclusters.

Noncovalent Interactions with Proteins Modify the Physicochemical Properties of a Molecular Switch.

It is reported that spiropyran-a widely investigated molecular photoswitch-can be stabilized in aqueous environments in the presence of a variety of proteins, including human serum albumin, insulin fibrils, lysozyme, and glucose oxidase. The optical properties of the complexed photoswitch are protein dependent, with human serum albumin providing the spiropyran with emission features previously observed for a photoswitch confined in media of high viscosity. Despite being bound to the protein molecules, spiropyran can undergo a ring-opening reaction upon exposure to UV light. This photoisomerization process can affect the properties of the proteins: here, it is shown that the electrical conduction through human serum albumin to which the spiropyran is bound increases following the ring-opening reaction.

Design of BODIPY Dyes as Photosensitisers in Multicomponent Catalyst Systems for Light-Driven Hydrogen Production.

A study of visible-light-driven hydrogen production using a multicomponent system consisting of different boron dipyrromethene (BODIPY) dyes, triethylamine and [{Pd(PPh3)Cl2}2] from THF/water mixtures is presented. A trio of meso-mesityl BODIPY dyes display the best activities and long-term stabilities of more than ten days with the 2,6-diiodo derivative showing the best performance.

Axially chiral BODIPY DYEmers: an apparent exception to the exciton chirality rule.

The exciton chirality method (ECM) is commonly recognized as one of the best approaches to assign the absolute configuration of biaryls. This paper reports the first exception to this method for a simple biaryl system. ECD and VCD measurements in combination with DFT (B3LYP/6-311G*), TDDFT (CAM-B3LYP/6-311G*), and Coupled-Cluster (RI-SCS-CC2) calculations were used to determine the absolute configurations of axially chiral BODIPY DYEmers. The ECM fails to predict the sign of the intense CD couplet at 500 nm of the 1,1'-coupled dimer. The odd behavior was rationalized by considering the strong transition magnetic dipole associated with the 500 nm transition, which leads to an unexpected dominance of the µm coupling at the expense of the µµ one in these compounds. This is the first case in which a strong µm coupling hampers the use of the ECM, but this behavior should not be restricted to the BODIPY chromophore.

Conjugated BODIPY DYEmers by metathesis reactions.

Boron dipyrrin (BODIPY) DYEmers bridged by conjugating ethynylene and ethenylene moieties can be prepared through metal-promoted metathesis reactions. Alkyne metathesis was advantageous over alkene metathesis and Stille coupling for BODIPY substrates, but also showed specific restrictions with respect to steric encumbrance and regioselectivity. All derivatives with unhindered rotations along the bridges reside in a coplanar minimum conformation. For a hindered ß-ethenylene-bridged DYEmer, the shifts in the (1) H NMR spectrum indicate a significant loss of coplanarity and conjugation. The electronic interactions of the BODIPY subchromophores, visualized by optical spectra and cyclic voltammograms, deviate significantly from those found for nonconjugated and excitonically coupled DYEmers. The observed properties can be rationalized in each case by the respective strength of conjugation through the α or ß position, the degree of coplanarity, and conformational dynamics.

Sulfur-bridged BODIPY DYEmers.

Reactions of BODIPY monomers with sulfur nucleophiles and electrophiles result in the formation of new BODIPY dimers. Mono- and disulfur bridges are established, and the new dyestuff molecules were studied with respect to their structural, optical, and electrochemical properties. X-ray diffraction analyses reveal individual angulated orientations of the BODIPY subunits in all cases. DFT calculations provide solution conformers of the DYEmers which deviate in a specific manner from the crystallographic results. Clear exciton-like splittings are observed in the absorption spectra, with maxima at up to 628 nm, in combination with the expected weak fluorescence in polar solvents. A strong communication between the BODIPY subunits was detected by cyclic voltammetry, where two separated one-electron oxidation and reduction waves with peak-to-peak potential differences of 120-400 mV are observed. The qualitative applicability of the exciton model by Kasha for the interpretation of the absorption spectral shape with respect to the conformational state, subunit orientation and distance, and conjugation through the different sulfur bridges, is discussed in detail for the new BODIPY derivatives. This work is part of our concept of DYEmers, where the covalent oligomerisation of BODIPY-type dye molecules with close distances is leading to new functional dyes with predictable properties.

Left ventricular diastolic function in type 2 diabetes mellitus is associated with myocardial triglyceride content but not with impaired myocardial perfusion reserve.

PURPOSE: To study myocardial perfusion reserve and myocellular metabolic alterations indicated by triglyceride content as possible causes of diastolic dysfunction in patients with type 2 diabetes mellitus, preserved systolic function, and without clinically evident coronary artery disease. MATERIALS AND METHODS: Patients with type 2 diabetes mellitus (n = 42) underwent cardiac magnetic resonance (CMR) for quantification of 1) myocardial contractility by strain-encoded MR (SENC); 2) myocardial triglyceride content by proton magnetic resonance spectroscopy ((1) H-MRS); and 3) myocardial perfusion reserve during pharmacologic hyperemia. Age-matched healthy volunteers (n = 16) also underwent CMR to acquire normal values for myocardial strain and perfusion reserve. RESULTS: Stress CMR procedures were successfully performed in all subjects, and no regional inducible perfusion defects were observed in type 2 diabetes mellitus patients. Diastolic strain rate and myocardial perfusion reserve were significantly impaired in patients with type 2 diabetes mellitus compared to control subjects (P < 0.001 for both). Interestingly, impaired diastolic function in type 2 diabetes mellitus was not associated with impaired myocardial perfusion reserve (r = 0.12, P = NS). Conversely a significant association was observed between diastolic dysfunction and myocardial triglyceride content (r = -0.71, P < 0.001), which proved to be independent of age, gender, diabetes duration, blood pressure, and fasting blood glucose. CONCLUSION: Myocardial steatosis may represent an early marker of diabetic heart disease, triggering subclinical myocardial dysfunction irrespective of myocardial perfusion reserve.

Chemical and electrochemical dimerization of BODIPY compounds: electrogenerated chemiluminescent detection of dimer formation.

The electrochemistry of several difluoroboradiaza-s-indacene (BODIPY) compounds lacking substituent groups in the meso (8)- and/or 3 (α)-positions was investigated. Chemical and electrochemical dimerization was demonstrated, and the dimerization depended on the character of substitution. The chemical dimerization was achieved by oxidative coupling using FeCl(3) in CH(2)Cl(2) at 0 °C. The electrochemical dimerization proceeded via anodic oxidation to the radical cation and monitored by both cyclic voltammetry (CV) and electrogenerated chemiluminescence (ECL). An available open 3-position was important for the formation of the dimer. The resulting 3,3'-dimer produced a second peak in the CV oxidation and also the appearance of a longer wavelength ECL peak at 656 nm, which is considerably shifted from the parent peak at 532 nm. No dimerization was seen for BODIPY molecules in which only the meso 8-position was unsubstituted, either by chemical or electrochemical means, demonstrating that dimerization occurs at position 3.

Synthesis, photophysical, electrochemical, and electrogenerated chemiluminescence studies. Multiple sequential electron transfers in BODIPY monomers, dimers, trimers, and polymer.

Synthesis of the C(8) BODIPY monomers, dimers, and trimers, a C(8) polymer, and N(8) aza-BODIPY monomer and dimer was carried out. Methyl and mesityl C(8)-substituted monomers, dimers, and trimers were used. Dimers, trimers, and polymer were formed chemically through the ß-ß (2/6) positions by oxidative coupling using FeCl(3). A red shift of the absorbance and fluorescence is observed with addition of monomer units from monomer to polymer for C(8) dyes. The aza-BODIPY dye shows red-shifted absorbance and fluorescence compared with the C(8) analogue. Cyclic voltammetry shows one, two, and three one-electron waves on both reduction and oxidation for the monomer, dimer, and trimer, respectively, for the C(8) BODIPYs. The separation for the reduction peaks for the C(8) dimers is 0.12 V compared with 0.22 V for the oxidation, while the trimers show separations of 0.09 V between reduction peaks and 0.13 V for oxidation peaks. The larger separations between the second and third peaks, 0.25 V for the oxidation and 0.2 V for the reduction, are consistent with a larger energy to remove or add a third electron compared with the second one. The BODIPY polymer shows the presence of many sequential one-electron waves with a small separation. These results provide evidence for significant electronic interactions between different monomer units. The aza-BODIPY dye shows a reduction peak 0.8 V more positive compared to the C(8) compound. Aza-BODIPY dimer shows the appearance of four waves in dichloromethane. The separation between two consecutive waves is around 0.12 V for reduction compared with 0.2 V for oxidation, which is comparable with the results for the C(8) dyes. Electrogenerated chemiluminescence (ECL) of the different species was obtained, including weak ECL of the polymer.

Prognostic value of high-dose dobutamine stress magnetic resonance imaging in 1,493 consecutive patients: assessment of myocardial wall motion and perfusion.

OBJECTIVES: This study sought to determine the prognostic value of wall motion and perfusion assessment during high-dose dobutamine stress (DS) cardiac magnetic resonance imaging (MRI) in a large patient cohort. BACKGROUND: DS-MRI offers the possibility to integrate myocardial perfusion and wall motion analysis in a single examination for the detection of coronary artery disease (CAD). METHODS: A total of 1,493 consecutive patients with suspected or known CAD underwent DS-MRI, using a standard protocol in a 1.5-T magnetic resonance scanner. Wall motion and perfusion were assessed at baseline and during stress, and outcome data including cardiac death, nonfatal myocardial infarction ("hard events"), and "late" revascularization performed >90 days after the MR scans were collected during a 2 ± 1 year follow-up period. RESULTS: Fifty-three hard events, including 14 cardiac deaths and 39 nonfatal infarctions, occurred during the follow-up period, whereas 85 patients underwent "late" revascularization. Using multivariable regression analysis, an abnormal result for wall motion or perfusion during stress yielded the strongest independent prognostic value for both hard events and late revascularization, clearly surpassing that of clinical and baseline magnetic resonance parameters (for wall motion: adjusted hazard ratio [HR] of 5.9 [95% confidence interval (CI): 2.5 to 13.6] for hard events and of 3.1 [95% CI: 1.7 to 5.6] for late revascularization, and for perfusion: adjusted HR of 5.4 [95% CI: 2.3 to 12.9] for hard events and of 6.2 [95% CI: 3.3 to 11.3] for late revascularization, p < 0.001 for all). CONCLUSIONS: DS-MRI can accurately identify patients who are at increased risk for cardiac death and myocardial infarction, separating them from those with normal findings, who have very low risk for future cardiac events. (Prognostic Value of High Dose Dobutamine Stress Magnetic Resonance Imaging; NCT00837005).