Regioselective stepwise bromination of boron dipyrromethene (BODIPY) dyes

Halogenated BODIPYs are important synthetic precursors and potential sensitizers for photodynamic therapy (PDT). Electrophilic bromination of pyrrolic-unsubstituted BODIPYs using bromine regioselectively generated mono- to heptabromoBODIPYs in a stepwise fashion in good to excellent yields. These resultant bromoBODIPYs were applied for regioselective substitution and Suzuki coupling reaction to generate BODIPYs 4, 5, 6, and 7 in good to excellent yields. According to NMR and X-ray analysis results, the stepwise bromination first takes place at 2,6-, then at 3,5-, and eventually at 1,7-positions, whereas the regioselective substitution occurs first at 3,5- then at 1,7-positions of the chromophore. The spectroscopic properties of these resultant BODIPYs were studied, which shows the potential application of these bromoBODIPYs as sensitizers for PDT.     

1,7-Disubstituted boron dipyrromethene (BODIPY) dyes: synthesis and spectroscopic properties

1,7-Dihalogenated boron dipyrromethene dyes were successfully synthesized and substituted, thus providing an entry to the final, elusive reactivity pattern. The spectroscopic properties of 1,7-disubstituted BODIPY dyes were studied and are discussed as a function of their structure.     

A novel fluorescent probe for zinc ion based on boron dipyrromethene (BODIPY) chromophore

ZnAB has the combined structure of N,N-bis(2-pyridylmethyl)ethylenediamine as a specific chelater for Zn(2+) and 1,3,5,7-tetramethyl-8-phenyl-boron dipyrromethene as a fluorophore. Complexation of ZnAB with Zn(2+) produces a remarkable enhancement of fluorescence intensity. ZnAB has the advantages of less sensitivity to solvent polarity and pH than fluorescein-based Zn(2+) probes. Furthermore, it is not influenced by other cations, such as Na(+), K(+), Ca(2+), and Mg(2+), which exist at high concentrations under physiological conditions, even at 2.5 mM. The results show that ZnAB is a Zn(2+) probe suitable for biological applications.     

Conformationally restricted dipyrromethene boron difluoride (BODIPY) dyes: highly fluorescent, multicolored probes for cellular imaging

Novel fluorescent, conformationally restricted dipyrromethene boron difluoride (BODIPY) dyes have been prepared by introducing a naphthalenyl group at the meso position of the BODIPY core. These BODIPY dyes exhibit increased fluorescence quantum yields compared with dyes that have a meso-position phenyl group with internal rotation. The absorption and emission wavelengths of such conformationally restricted BODIPY dyes can be easily tuned to the near-IR range by derivatization through a condensation reaction with benzaldehyde derivatives. The two-photon absorption properties of these BODIPY dyes were also investigated and the results show that they exhibit increased two-photon excited fluorescence compared to analogue dyes that contain a phenyl group. The one- and two-photon fluorescence imaging of living cells by using selected BODIPY dyes has been successfully demonstrated.     

Incorporating BODIPY fluorophores into tetrakis(arylethynyl)benzenes

Six structural isomers of a tetrakis(arylethynyl)benzene (TAEB) chromophore functionalized with dibutylamine and BODIPY moieties as the corresponding donor and acceptor units were prepared. To evaluate the effectiveness of the donor group, two TAEB molecules and three structurally related bis(arylethynyl)benzene (BAEB) isomers containing only acceptors were also synthesized. The electronic absorption and emission spectra of each series were examined. Additionally, computational studies were employed to corroborate the relative energy levels and gaps present in each series.     

Mimicking photosynthetic antenna-reaction-center complexes with a (boron dipyrromethene)3-porphyrin-C60 pentad

A highly efficient functional mimic of the photosynthetic antenna-reaction-center complexes has been designed and synthesized. The model contains a zinc(II) porphyrin (ZnP) core, which is connected to three boron dipyrromethene (BDP) units by click chemistry, and to a C(60) moiety using the Prato procedure. The compound has been characterized using various spectroscopic methods. The intramolecular photoinduced processes of this pentad have also been studied in detail with steady-state and time-resolved absorption and emission spectroscopic methods, both in polar benzonitrile and nonpolar toluene. The BDP units serve as the antennae, which upon excitation undergo singlet-singlet energy transfer to the porphyrin core. This is then followed by an efficient electron transfer to the C(60) moiety, resulting in the formation of the singlet charge-separated state (BDP)(3)-ZnP(·+) -C(60)(·-) , which has a lifetime of 476 and 1000 ps in benzonitrile and toluene, respectively. Interestingly, a slow charge-recombination process (k(CR)(t)=2.6×10(6) s(-1)) and a long-lived triplet charge-separated state (τ(CS)(T)=385 ns) were detected in polar benzonitrile by nanosecond transient measurements.     

Fluorescent boron dipyrromethene (Bodipy) dyes having two and four vinyl residues

Several new extended fluorescent dyes have been prepared by stepwise functionalisation of the methyl groups located in the 1, 3, 5, and 7 substitution positions of Bodipy dyes. In one case, a ferrocene residue has been connected, giving rise to severe fluorescence quenching and a rich redox behavior. The stepwise syntheses were largely based on Knoevenagel reactions allowing the attachment of three different modules in a tetravinyl configuration. Most of these dyes exhibit reversible formation of radical cations and radical anions, as well as an irreversible formation of dications and dianions. Spectroscopic examination of the dyes under various conditions including the presence of acid leads to the conclusion that the delocalization is more effective in the 3,5-substitution positions than in the 1,7-positions. These novel dyes have absorption and emission wavelengths spanning the ranges of 573-718 nm and 585-778 nm, respectively.     

Rational design of a calcium-binding protein

Calcium ions play key roles as structural components in biomineralization and as a second messenger in signaling pathways. We have introduced a de novo designed calcium-binding site into the framework of a non-calcium-binding protein, domain 1 of CD2. The resulting protein selectively binds calcium over magnesium with calcium-binding affinity comparable to that of natural extracellular calcium-binding proteins (K(d) of 50 microM). This experiment is the first successful metalloprotein design that has a high coordination number (seven) metal-binding site constructed into a beta-sheet protein. Our results demonstrate the feasibility of designing a single calcium-binding site into a host protein, taking into account only local properties of a calcium-binding site obtained by a survey of natural calcium-binding proteins and chelators. The resulting site exhibits strong metal selectivity, suggesting that it should now be feasible to understand and manipulate signaling processes by designing novel calcium-modulated proteins with specifically desired functions and to affect their stability.     

Rational Design of Boradiazaindacene (BODIPY)‐Based Functional Molecules

Three boradiazaindacene (BODIPY) dyes with different‐coloured (greenish‐yellow, orange and red) fluorescence and good Stokes shifts were synthesised starting from the greenish‐yellow BODIPY dye PM546. The high Stokes shifts of the dyes are due to the release of the steric strain in their excited states relative to that in the highly twisted ground states. One of these compounds might be a useful water‐soluble fluorophore, whereas the other two are promising H⁺ sensors.     

Stereochemically stable double-helicate dinuclear complexes of bis(dipyrromethene)s: a chiroptical study

Helical zinc(II) complexes of bis(dipyrromethene)s bearing homochiral amide substituents were synthesized. Analysis of the products by chiral HPLC showed two diastereomeric major products and showed that dipyrromethene double-nuclear helicates are stereochemically stable and do not interconvert. Circular dichroism (CD) studies showed that the complexation reactions had proceeded with modest diastereomeric excesses. Analysis of an analogous symmetric zinc(II) bis(dipyrromethene) lacking homochiral substituents that could act as chromophores discounted induced CD by the chiral auxiliaries.     

Charge separation in a nonfluorescent donor-acceptor dyad derived from boron dipyrromethene dye, leading to photocurrent generation

Boron dipyrromethene (BODIPY), which is commonly used as an energy absorbing and transferring antenna molecule, has been modified to contain an electron donor moiety, 8-(2,4,5-trimethoxyphenyl)-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (MEOPHBDP). The photoinduced electron transfer from a 2,4,5-trimethoxyphenyl moiety to a BODIPY moiety of MEOPHBDP in acetonitrile was observed by femtosecond laser flash photolysis measurements. The lifetime of the charge-separated state of MEOPHBDP was 59 ps at 298 K. The dye-sensitized solar cells (DSSC) were prepared using MEOPHBDP with carboxylic acid (MEOPHBDP-COOH) and a reference BODIPY dye having no electron donor moiety. The photovoltaic measurements were performed using a standard two-electrode system consisting of a working electrode and a Pt sputtered electrode in methoxyacetonitrile containing 0.5 M iodide and 0.05 M I(2). The photoelectrochemical properties of DSSC with MEOPHBDP are compared with those with a reference BODIPY dye.     

A general synthetic strategy for the design of new BODIPY fluorophores based on pyrroles with polycondensed aromatic and metallocene substituents

BODIPYrrole: A general strategy for the design of novel BODIPY fluorophores based on pyrroles with polycondensed aromatic and metallocene substituents has been developed. The strategy involves the acylation of the condensed substituent and treatment of the acylated derivative (as oxime) with acetylene in MOH/DMSO (M = alkali metal) to give pyrroles that were then used for assembly of the BODIPY fluorophores (see scheme).     

Highly sensitive fluorescence probes for nitric oxide based on boron dipyrromethene chromophore-rational design of potentially useful bioimaging fluorescence probe

Boron dipyrromethene (BODIPY) is known to have a high quantum yield (phi) of fluorescence in aqueous solution but has not been utilized much for biological applications, compared to fluorescein. We developed 8-(3,4-diaminophenyl)-2,6-bis(2-carboxyethyl)-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (DAMBO-P(H)), based on the BODIPY chromophore, as a highly sensitive fluorescence probe for nitric oxide (NO). DAMBO-P(H) had a low phi value of 0.002, whereas its triazole derivative (DAMBO-P(H)-T), the product of the reaction of DAMBO-P(H) with NO, fluoresced strongly (phi = 0.74). The change of the fluorescence intensity was found to be controlled by an intramolecular photoinduced electron transfer (PeT) mechanism. The strategy for development of DAMBO-P(H) was as follows: (1) in order to design a highly sensitive probe of NO, the reactivity of o-phenylenediamine derivatives as NO-reactive moieties was examined using 4,5-diaminofluorescein (DAF-2, a widely used NO fluorescence probe), (2) in order to avoid pH-dependency of the fluorescence intensity, the PeT process was controlled by modulating the spectroscopic and electrochemical properties of BODIPY chromophores according to the Rehm-Weller equation based on measurement of excitation energies of chromophores, ground-state reduction potentials of PeT acceptors (BODIPYs), and calculation of the HOMO energy level of the PeT donor (o-phenylenediamine moiety) at the B3LYP/6-31G level, (3) in order to avoid quenching of fluorescence by stacking of the probes and to obtain probes suitable for biological applications, hydrophilic functional groups were introduced. This strategy should be applicable for the rational design of other novel and potentially useful bioimaging fluorescence probes.     

EDA study of pi-conjugation in tunable Bis(gem-diethynylethene) fluorophores

The strength of pi-conjugation in a family of bis(gem-diethynylethene) fluorophores is estimated within the density functional theory framework using the energy decomposition analysis (EDA) method. The observed very good linear correlations between the calculated pi-conjugation and the experimental values for the UV absorption and fluorescence emission for this series of compounds suggest that the values given by the EDA are useful for the interpretation and prediction of photochemical properties of the molecules. The calculated data predict that adequate modifications in the core moiety of the molecule such as pi-donor substituents in the aromatic ring or in the periphery of the bis-enedyine unit like pi-acceptor groups placed in the para position of the aryl substituent increase the total pi-conjugation in the systems and thus provoke significant changes in both the absorption and emission spectra leading to large Stokes shifts. The effect of such substituents is quantitatively predicted by the EDA data.     

Substitution of hydroxide by fluoride at the boron center of a BODIPY dye

4-Chloro-4-phenyl-1,3,5,7,8-pentamethyl-3a,4a-diaza-4-bora-s-indacene (2) has been synthesized, structurally characterized and converted into the corresponding hydroxide derivative 4-hydroxo-4-phenyl-1,3,5,7,8-pentamethyl-3a,4a-diaza-4-bora-s-indacene (3). This boron hydroxide derivative reacts with fluoride anions under acidic conditions to afford the corresponding fluoride derivative 4-fluoro-4-phenyl-1,3,5,7,8-pentamethyl-3a,4a-diaza-4-bora-s-indacene (4). This simple reaction may become useful for the incorporation of [¹⁸F]-fluoride and may serve for the preparation of radiolabeled BODIPY derivatives.     

Membrane dynamics of a myelin-like giant multilamellar vesicle applicable to a self-reproducing system

A real time observation of a myelin-like giant multilamellar vesicle (mGMV) revealed that it divided into relatively small mGMVs when an aqueous solution of an electrolyte was added. Furthermore, the mGMV showed a division process accompanied by the growth of the dividing mGMVs when a bolaamphiphile which was composed of an electrolyte unit and a vesicular amphiphile unit was added. This vesicular system can be regarded as a self-reproduction of mGMV, where the added amphiphile acts as a supplier of both the vesicular amphiphile and the division initiator.     

Rational design of a NIR-emitting Pd(II) sensor via oxidative cyclization to form a benzoxazole ring

By using the substituent effect to tune the palladium(II)-involved reactivity, a new probe is found to respond quantitatively to Pd(II). Unexpectedly, the probe gave an emission band in the desirable near-infrared (NIR) region (780 nm), thus providing the first NIR sensor for palladium detection.