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The asymmetric BODIPY 1 a (BODIPY=4,4-difluoro-4-bora-3a,4a-diaza- s-indacene), containing two chloro substituents at the 3,8-positions and a reactive 5-methyl group, was synthesized from the asymmetric dipyrroketone 3, which was readily obtained from available pyrrole 2 a. The reactivity of 3,8-dichloro-6-ethyl-1,2,5,7-tetramethyl-BODIPY 1 a was investigated by using four types of reactions. This versatile BODIPY undergoes regioselective Pd0-catalyzed Stille coupling reactions and/or regioselective nucleophilic addition/elimination reactions, first at the 8-chloro and then at the 3-chloro group, using a variety of organostannanes and N-, O-, and S-centered nucleophiles. On the other hand, the more reactive 5-methyl group undergoes regioselective Knoevenagel condensation with an aryl aldehyde to produce a monostyryl-BODIPY, and oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) gives the corresponding 5-formyl-BODIPY. Investigation of the reactivity of asymmetric BODIPY 1 a led to the preparation of a variety of functionalized BODIPYs with λmax of absorption and emission in the ranges 487-587 and 521-617 nm, respectively. The longest absorbing/emitting compound was the monostyryl-BODIPY 16, and the largest Stokes shift (49 nm) and fluorescence quantum yield (0.94) were measured for 5-thienyl-8-phenoxy-BODIPY 15. The structural properties (including 16 X-ray structures) of the new series of BODIPYs were investigated. [ABSTRACT FROM AUTHOR]

Symmetric dipyrrylketones 1 a, b were synthesized in two steps from the corresponding α-free pyrroles, by reaction with thiophosgene followed by oxidative hydrolysis under basic conditions. The dipyrrylketones produced the corresponding 5-chloro-dipyrrinium salts or 5-ethoxy-dipyrrins on reaction with phosgene or Meerwein's salt, respectively. Boron complexation of the dipyrrins afforded the corresponding 8-functionalized BODIPYs (borondipyrromethenes) in high yields. The 5-chloro-dipyrrinium salts reacted with methoxide or ethoxide ions to produce monopyrrole esters, presumably via a 5,5-dialkoxy-dipyrromethane intermediate. In contrast, 8-chloro-BODIPYs underwent a variety of nucleophilic substitutions of the chloro group in the presence of alkoxide ions, Grignard reagents, and thiols. In the presence of excess alkoxide or Grignard reagent, at room temperature or above, substitution at the boron center also occurred. The 8-chloro-BODIPY was a particularly useful reagent for the preparation of 8-aryl-, 8-alkyl-, and 8-vinyl-substituted BODIPYs in very high yields, using Pd0-catalyzed Stille cross-coupling reactions. The X-ray structures of eleven BODIPYs and two pyrroles are presented, and the spectroscopic properties of the synthesized BODIPYs are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Seven polyamine conjugates of a tri(p-carboranylmethylthio)tetrafluorophenylporphyrin were prepared in high yields by sequential substitution of the p-phenyl fluoride of tetrakis(pentafluorophenyl)porphyrin (TPPF), and investigated as boron delivery agents for boron neutron capture therapy (BNCT). The polyamines used were derivatives of the natural-occurring spermine with different lengths of the carbon chains, terminal primary amine groups and, in two of the conjugates, additional aminoethyl moieties. A tri(polyethylene glycol) conjugate was also synthesized for comparison purposes. The polyamine conjugates showed low dark cytotoxicity (IC50 >400μM) and low phototoxicity (IC50 >40μM at 1.5J/cm2). All polyamine conjugates, with one exception, showed higher uptake into human glioma T98G cells (up to 12-fold) than the PEG conjugate, and localized preferentially in the cell ER, Golgi and the lysosomes. Our results show that spermine derivatives can serve as effective carriers of boronated porphyrins for the BNCT of tumors. [Copyright &y& Elsevier]

Abstract: Five cationic porphyrins bearing one to four groups linked to the p-phenyl positions of 5,10,15,20-tetraphenylporphyrin (TPP) were synthesized in order to study the effect of overall charge and its distribution on the cellular uptake, phototoxicity and intracellular localization using human carcinoma HEp2 cells. The di-cationic porphyrins DADP-o and DADP-a accumulated the most within cells and preferentially localize within vesicular compartments and in mitochondria. Of these two only DADP-a was phototoxic to the cells (IC50 =3μM at 1J/cm2). The mono-cationic porphyrin MAP was found to be the most phototoxic of the series, and it localized mainly in lipid membranes, including the plasma membrane, ER, mitochondria, and Golgi. Both the tri-cationic porphyrin TRAP and the tetra-cationic porphyrin TEAP localized subcellularly mainly in the mitochondria, but of the two only TEAP showed moderate phototoxicity (IC50 =8μM at 1J/cm2). Our results suggest that MAP is the most promising PDT photosensitizer, and that both DADP-o and TRAP might find application as transport vehicles for therapeutics into cells. [Copyright &y& Elsevier]

Abstract: The structure of the ring-opened product from direct oxidation of meso-tetra-arylporphyrins has been controversial for three decades. Herein we show that bilitrienones 2 are obtained from oxidation of metal-free dodecasubstituted porphyrins 1 in the presence of sodium nitrite, trifluoroacetic acid, and air oxygen. The presence of the para-nonyl groups in 1b stabilized the corresponding bilitrienone 2b, which was characterized by X-ray crystallography. In the absence of the para-nonyl groups bilitrienone 2a undergoes a rapid hydration reaction, giving biladienone 3a as the major isolated product. The molecular structures of 2b and 3a, and the photochemical isomerization of 3a are discussed. [Copyright &y& Elsevier]

The high-yield preparation of metallo-benzoylbiliverdins 9, 10, and 11 from either oxidation of dodeca-substituted porphyrin 6 in the presence of NaNO2/TFA and air followed by metalation or by reaction of the Ni(II) or Cu(II) complexes of 6 with m-chloroperoxybenzoic acid in pyridine under air is reported. The X-ray structures of complexes 9 and 10 and the electrochemistry and spectroelectrochemistry of metallo-benzoylbiliverdins 9–11 are presented and discussed. [ABSTRACT FROM AUTHOR]

The total synthesis of a 5,15-di[3,5-(o-carboranylmethyl)phenyl]porphyrin 5, its zinc(II) complex 6, and the corresponding nido-carboranylporphyrins 7 and 8 are reported. The molecular structures of porphyrin 6 and of potassium nido-carborane were obtained and are described. The biodistribution of nido-carboranylporphyrins 7 and 8 in BALB/c mice bearing EMT-6 mammary tumors are presented and compared. Both compounds are effective tumor localizers and delivered therapeutic concentrations of boron to tumors (mean±standard deviation): 32.5±7.1 and 54.3±14 μg/g for 7 and 8, respectively, 2 days after the last of 3 injections of a total boron dose of 23 mg/kg body weight. The zinc(II) complex 8 was found to deliver 1.2–1.7 times higher amounts of boron to tumors than 7, with lower tumor-to-blood boron concentration ratios (9.8/1 and 4.7/1 for 7 and 8, respectively, 2 days after injections). The tumor-to-brain boron concentration ratios were >100/1 for both porphyrins 2 days after administration. Both nido-carboranylporphyrins 7 and 8 were well-tolerated at the concentrations used (75 and 78 mg/kg body weight, respectively) and no morbidity or mortality were observed in these studies. [Copyright &y& Elsevier]

Two meso-tetra[(nido-carboranylmethyl)phenyl]porphyrins (para- and meta-regioisomers) and their corresponding Zn(II) complexes have been synthesized with the aim of studying the effect of carborane distribution and metalation on the biological properties of this series of compounds. In vitro cell toxicity, uptake/efflux, and subcellular localization using rat 9L, mouse B16 and/or human U-373MG cells were evaluated. All four amphiphilic porphyrins display very low cytotoxicities and time- and concentration-dependent uptake by cells, which is influenced by serum proteins. Preliminary subcellular localization studies suggest that one of these compounds localizes in close proximity to the cell nucleus. All four nido-carboranylporphyrins show promise as boron-carriers for the boron neutron capture therapy of cancers, particularly the metal-free nido-carboranylporphyrins 5 and 12, which are able to deliver higher amount of boron to cells in vitro than the corresponding zinc complexes. [Copyright &y& Elsevier]

A series of β,β′-bicyclo-3,5-diaryl-BODIPYs were synthesized from the corresponding β,β′-bicyclo-3,5-diiodo-BODIPYs (1a,b) via Pd(0)-mediated Suzuki cross-coupling reactions in 82–92% yields. Subsequent aromatization with DDQ afforded the corresponding β,β′-dibenzo-aryl-BODIPYs, which showed red-shifted absorptions and emissions in the near-IR range. The dibenzo-appended BODIPYs showed characteristic 1H-, 13C-, 11B- and 19F-NMR shifts, and nearly planar conformations by X-ray crystallography. [ABSTRACT FROM AUTHOR]

The synthesis and reactivity of 3,8‐dibromo‐dodecafluoro‐benzo‐fused BOPHY 2 are reported, via SNAr with O‐, N‐ S‐ and C‐nucleophiles, and in Pd(0)‐catalyzed cross‐coupling reactions (Suzuki and Stille). The resulting perfluoro‐BOPHY derivatives were investigated for their reactivity in the presence of various nucleophiles. BOPHY 3 displays reversible color change and fluorescence quenching in the presence of bases (Et3N, DBU), whereas BOPHY 7 reacts preferentially at the α‐pyrrolic positions, and BOPHY 8 undergoes regioselective fluorine substitution in the presence of thiols. The structural and electronic features of the fluorinated BOPHYs were studied by TD‐DFT computations. In addition, their spectroscopic and cellular properties were investigated; BOPHY 10 shows the most red‐shifted absorption/emission (λmax 659/699 nm) and 7 the highest fluorescence (Φf=0.95), while all compounds studied showed low cytotoxicity toward human HEp2 cells and were efficiently internalized. [ABSTRACT FROM AUTHOR]

Catalytic hydrogenation of dibenzyl 5-dipyrroketone-2,9-dicarboxylates followed by decarboxylative iodination affords a 2,9-diiododipyrroketone which gives a 2,5,9-trichlorodipyrromethene hydrochloride after nucleophilic addition/elimination, with adventitious chloride to replace the two iodide groups. Treatment with BF3⋅Et2O gives a 3,5,8-trichloro-BODIPY that readily undergoes regioselective Stille coupling at the 8-position, or homo/mixed couplings at the 3,8- or 3,5- and 8-positions. Stepwise and controlled replacement of the 3,5- and 8-chlorine atoms using Stille reagents results in formation of a completely unsymmetrical trisubstituted BODIPY. Several examples of unsymmetrical BODIPYs were synthesized and characterized using this methodology. Structure features of new BODIPYs are discussed within the context of 14 new X-ray structures, and photophysical parameters of all new BODIPY compounds are reported and discussed. [ABSTRACT FROM AUTHOR]

Abstract: A series of red and near-IR fluorescent BODIPY conjugates, containing either one or two indolylstyryl groups at the 3- and/or 5-positions and a low molecular weight PEG or carbohydrate group, were synthesized using a Cu(I)-catalyzed azide–alkyne Huisgen cycloaddition (‘click’ reaction). All BODIPY conjugates show emission and fluorescence quantum yields in the ranges of 642–732 nm and 0.24–0.56, respectively, and Stokes' shifts of ca. 30 nm. In vitro cellular investigations using human carcinoma HEp2 cells showed that all BODIPYs are non-toxic, both in the absence and presence of light (1 J/cm2), up to 100 μM concentrations. The PEG and galactose conjugates were more efficient at cell internalization than the unconjugated BODIPYs. The mono-indolylstyryl–BODIPYs showed higher cellular uptake (about five-fold) compared with the di-indolylstyryl–BODIPYs, and higher fluorescence quantum yields. [Copyright &y& Elsevier]

Abstract: A new family of porphyrins containing different groups in meso positions was synthesized by Suzuki coupling reaction of meso mono- and dibromo-diarylporphyrins with several boronate esters, catalyzed by palladium organometallic complexes. These procedures gave high yields of unsymmetric porphyrins bearing carboxylate anchoring groups, with enhanced absorptions in the red and showing no tendency for aggregation in toluene or THF solutions. Such properties are of interest for application in dye-sensitized solar cells. [Copyright &y& Elsevier]

Abstract: The syntheses and spectroscopic properties of a series of pegylated zinc(II)-phthalocyanines (Zn-Pcs) containing one, two, or eight tri(ethylene glycol) chains are described. The single molecular structure of a phthalonitrile precursor containing one hydroxyl and one PEG group, and its unique intermolecular hydrogen bonding are presented. The pegylated Pcs are highly soluble in polar organic solvents and have fluorescence quantum yields in the range 0.08–0.28. [Copyright &y& Elsevier]

Abstract: Syntheses of two new cobaltacarborane–phthalocyanine conjugates, one anionic (Pc 6) and one zwitterionic (Pc 7), were accomplished via cyclotetramerization of the corresponding cobaltacarborane-substituted phthalonitriles (4 or 5) with excess phthalonitrile in quinoline. X-ray structures of two phthalonitrile precursors (2 and 3) were obtained and are discussed, and the absorption and emission properties of the two cobaltacarborane–phthalocyanine conjugates in several solvents were investigated. The anionic conjugate 6 exists mainly as a monomer in polar organic solvents and has fluorescence quantum yields in the region 0.2–0.3. The zwitterionic conjugate 7 aggregates in solution and displays lower quantum yields ∼0.1 in organic solvents. [Copyright &y& Elsevier]

Mono-(l)-aspartylchlorin-e6 (also known as Talaporfin, NPe6, MACE, and most recently LS-11) is a potent sensitizer for photodynamic therapy that is currently undergoing clinical trials. Using a combination of unambiguous partial synthesis from pheophytin-a and methyl pheophorbide-a, NMR spectroscopy, and single crystal X-ray diffraction, the structure of mono-(l)-aspartylchlorin-e6 is definitively shown to be the isomer in which the aspartyl residue is attached at the 152-side chain position. This conclusion is contrary to earlier assumptions, but affirms the conclusions of a study based on NMR spectroscopy; a rationale for the unique formation of the 152-aspartyl derivative is proposed. [ABSTRACT FROM AUTHOR]

Abstract: The total syntheses of four PEG-functionalized porphyrins, containing one to four low molecular weight PEG chains linked via amide bonds to the para-phenyl positions of meso-tetraphenylporphyrin, are reported. The hydrophobic character of the PEG-porphyrins decreases with the number of PEG chains linked to the porphyrin ring, while their tendency for aggregation in buffered aqueous solution increases. The porphyrins containing one or two PEG chains accumulated within human HEp2 cells to a much higher extent than those having three or four PEGs at the macrocycle periphery. All PEG-porphyrins were found to be non-toxic in the dark, and only those containing one or two PEG chains were phototoxic (IC50 =2μM at 1J/cm2 light dose). The preferential sites of subcellular localization of the porphyrins containing one or two PEG chains were found to be the mitochondria and endoplasmic reticulum (ER), while those containing three or four PEG chains localize preferentially in the lysosomes. [Copyright &y& Elsevier]

The efficient one-step synthesis of oxacalixarene-bisporphyrins and higher oligomers from readily available starting materials is described. The X-ray structure of one oxacalix[4]arene-locked cofacial bisporphyrin, prepared in 91% yield, shows an 1,3-alternate conformation of the molecule with partial overlap of the two porphyrin rings. ¹H NMR data supports a similar conformation in solution. The absorption and emission spectra of oxacalixarene-porphyrins are briefly discussed. [ABSTRACT FROM AUTHOR]

Abstract: In the presence of excess dimethylacetylene dicarboxylate (DMAD), nickel(II) pyrrolo[3,4-b]porphyrins undergo both Diels–Alder cycloaddition and Michael addition in toluene to give two bis-adducts, identified as compounds 4 and 5 ; the reaction can be accelerated by the addition of Lewis or Brønsted–Lowry acids. Refluxing the reaction mixture in 1,2,4-trichlorobenzene (220°C) leads to a nickel(II) monobenzoporphyrin 2 as the main product. The structure of compound 4 was confirmed by X-ray crystallography. [Copyright &y& Elsevier]

The anodic oxidation of a carborane-substituted pyrrole leads to the formation of an electroactive polymer film (σ∼10−1 S cm−1) which shows a strongly increased overoxidation resistance in comparison with unsubstituted polypyrrole. [Copyright &y& Elsevier]

Abstract: The syntheses of two new A3B-type Zn(II)-phthalocyanines (Zn-Pcs) containing either one or two cobaltacarborane residues are reported, and the X-ray structure of a key phthalonitrile precursor is presented. The Zn-Pcs are highly soluble and exist as monomers in polar organic solvents. [Copyright &y& Elsevier]

A series of linker‐free aza‐BODIPY‐glutamine conjugates were synthesized and investigated, both experimentally and computationally. The structures of the aza‐BODIPYs were confirmed spectroscopically, and in the case of 3a an X‐ray structure was obtained. All aza‐BODIPYs show intense absorption bands between 642–667 nm and fluorescence emissions between 691–703 nm. The fluorescence quantum yields of the 2,6‐unsubstituted compounds 1a–4a were found to be Φf ≈ 0.2 in chloroform, while those of the corresponding 2,6‐dibrominated derivatives 1b–4b were less than 0.01. The cytotoxicity and cellular uptake of all aza‐BODIPYs were investigated in human carcinoma HEp2 cells. The most cytotoxic aza‐BODIPYs were found to be 3a and 3b, due to the presence of the cyclic N,O‐bidentate amino acid ring, rather than the presence of the 2,6‐bromine atoms. The results show that the mode of glutamine conjugation to the aza‐BODIPY determines the stability and cytotoxicity of the conjugates. [ABSTRACT FROM AUTHOR]

Abstract The cationic Ga(III) and Zn(II) phthalocyanines carrying N -methyl-pyridinium groups at eight peripheral β-positionshave been synthesized. These complexes are highly soluble in dimethyl sulfoxide (DMSO) and moderately soluble in water and phosphate buffered saline (PBS); both Ga(III)Cl and Zn(II) complexes have shown no aggregation in water up to 1.2 × 10−4 and 1.5 × 10−5 M, respectively. A higher water-solubility of Ga(III)Cl complex as compared to Zn(II) complex is ascribed to the presence of an axially coordinated chloride. The spectroscopic properties, photogeneration of singlet oxygen (1O 2), and cytotoxicity of these complexes have been investigated. The absolute quantum yields (ΦΔ absolute) for the photogeneration of singlet oxygen using Ga(III)Cl and Zn(II) complexes have been determined to be 4.4 and 5.3%, respectively, in DMSO solution. The cytotoxicity and intracellular sites of localization of Ga(III)Cl and Zn(II) complexes have been evaluated in human HEp2 cells. Both complexes, localized intracellularly in multiple organelles, have shown no cytotoxicity in the dark. Upon exposure to a low light dose (1.5 J/cm2), however, Zn(II) complex has exhibited a high photocytotoxicity. The result suggests that Zn(II) complex can be considered as a potential photosensitizer for Photodynamic therapy (PDT). Graphical abstract The cationic Ga(III) and Zn(II) phthalocyanines carrying N -methyl-pyridinium groups at eight peripheral β-positions have been synthesized. The spectroscopic properties, photogeneration of singlet oxygen, and cytotoxicity of these complexes have been investigated. The cationic Zn(II) complex has exhibited a high photocytotoxicity in human HEp2 cells. Unlabelled Image Highlights • Cationic phthalocyanines carring N-methyl-pyridinium groups have been synthesized. • Singlet oxygen generation by the cationic phthalocyanines has been observed. • Upon exposure to a low light dose, cationic Zn complex shows highly photo-toxicity. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Patterned arrays of nanoholes and nanorings were prepared using colloidal lithography combined with steps of solution immersion and vapor deposition of organosilanes. Samples prepared with colloidal lithography exhibit millions of reproducible test structures with a periodic arrangement throughout areas of the surface according to the dimensions and spacing of the particle mask. Views of the size and morphology of nanopatterns obtained with atomic force microscopy (AFM) can provide information of progressive steps of chemical reactions as nanostructures are grown within spatially confined areas surrounded by a resist film. A surface mask of colloidal latex or silica spheres was used to protect discrete areas of a Si(111) substrate from the deposition of organosilanes. When the mask was removed, the uncovered areas of the surface revealed regularly-shaped, small sites of uncovered substrate available for further reaction steps to build hierarchical surface structures. Nanostructures of zinc phthalocyanines (ZnPcs) were constructed using amine-terminated nanopatterns as sites for binding. Spatial selectivity was achieved for directing the attachment of ZnPcs to the surface using resist films of 2-methoxy(polyethyleneoxy)propyl]trichlorosilane (PEO-silane) and also with octadecyltrimethoxysilane (OTMS). The molecule chosen as a linker was (3-aminopropyl)triethoxysilane (APTES) which presents an amine group at the interface. In general, phthalocyanine molecules tend to bind in a coplanar orientation by physisorption to the surface and can stack together through pi-pi interactions between adjacent macrocycles. However, the nature of the substituents will also influence whether the molecules assemble on surfaces in a side-on orientation or with the macrocycle oriented in a coplanar arrangement. Hydroxyl and isothiocyanate pendant groups were attached to the macrocycles of ZnPcs chosen for this study, to investigate conformational differences when attached to APTES nanopatterns. The size and morphology of nanostructures was visualized and sensitively measured with tapping-mode AFM. The elastic response of samples patterned with ZnPc was mapped with force modulation AFM. Changes in the height of nanostructures indicate whether the macrocycles are oriented upright or parallel to the surface plane, or if multilayers were formed. [ABSTRACT FROM AUTHOR]

A series of BODIPYs bearing one (4b,c), two (6a) or three (3b) glucose units attached to the meso(8) and the boron atom positions were synthesized using a Cu(i)-catalyzed Huisgen cycloaddition reaction. The resulting 1,2,3-triazole-BODIPYs were characterized by 1H, 13C and 11B NMR, HRMS, and in the case of 4a and 4b by X-ray crystallography. Triazole-BODIPYs 3b, 4b and 6a were highly permeable in cells and non-toxic to human HEp2 cells, both in the dark and upon light irradiation (IC50 ＞ 100 μM). The time-dependent cellular uptake increased with the increase number of glucose units. [ABSTRACT FROM AUTHOR]

A new synthetic method to build aryl-fused 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPYs) is reported. The intramolecular cyclization step was completed in a short time (1-2 h) and in high yields (>90%), due to the intrinsic rigid structural conformation of the precursor BODIPY and the high reactivity of its 1,7-bromo groups. The [a]phenanthrene-fused BODIPYs 4a-c were characterized by NMR spectroscopy, HRMS, DFT calculations, and, in the case of 4a, by X-ray crystallography. Spectroscopic studies show that 4a-c strongly absorb and emit in the NIR spectral region, in the range 642-701 nm. In addition, BODIPYs 4b and 4c exhibit no toxicity in the light or dark in HEp2 cells and accumulate intracellularly in a time-dependent manner, mainly in the cell endoplasmic reticulum. These results suggest the potential use of [a]phenanthrene-fused BODIPYs as NIR bioimaging probes. [ABSTRACT FROM AUTHOR]

We report the synthesis and investigation of an unprecedented 8-heteroaryl-fused BODIPY 4. This compound exhibits enhanced π-π stacking in the solid state, unusually large blue-shifts in the absorbance and emission spectra, and higher fluorescence quantum yield than its unfused precursor; DFT calculations suggest a small energy gap for 4 and strong electronic communication between the 8-OPh and the BODIPY core. [ABSTRACT FROM AUTHOR]

A series of push-pull BODIPYs bearing multiple electron-donating and electron-acceptor groups were synthesized regioselectively from 2,3,5,6,8-pentachloro-BODIPY, and characterized by NMR spectroscopy, HRMS, and X-ray crystallography. The influence of the push-pull substituents on the spectroscopic and electrochemical properties of BODIPYs was investigated. Bathochromic shifts were observed for both absorbance (up to 37 nm) and emission (up to 60 nm) in different solvents upon introduction of the push-pull moieties. DFT calculations, consistent with the spectroscopic and cyclic voltammetry studies, show decreased HOMO-LUMO energy gaps upon the installation of the push-pull moieties. BODIPY 7 bearing thienyl groups on the 2 and 6 positions showed the largest λmax for both absorption (635-653 nm) and emission (706-707 nm), but also the lowest fluorescence quantum yields. All BODIPYs were nontoxic in the dark (IC50 > 200 μM) and showed low phototoxicity (IC50 > 100 μM, 1.5 J/cm2) toward human HEp2 cells. Despite the relatively low fluorescence quantum yields, the push-pull BODIPYS were effective for cell imaging, readily accumulating within cells and localizing mainly in the ER and Golgi. Our structure-property studies can guide future design of functionalized BODIPYs for various applications, including bioimaging and in dye-sensitized solar cells. [ABSTRACT FROM AUTHOR]

A series of 5,5′-functionalized 2,2′-( ortho -carboranyl)bisthiophene with bromo, vinyl, trimethylsilylethyne, N -methylpyrrole or thienyl groups was synthesized and all compounds were characterized by NMR, MS, and X-ray analysis. Electrochemical characterizations of 12a,b and 13a,b were conducted, and the di(thienyl- N -methylpyrrole)- o -carborane 12a and di(bisthienyl)- o -carborane 12b were successfully electropolymerized on a suitable anode to produce the corresponding conducting polymers. DFT calculations are consistent with the electrochemical data. [ABSTRACT FROM AUTHOR]

A series of seven BODIPYs functionalized with ortho-carborane groups at the 8(meso) or 3/5(α) position were synthesized and characterized by NMR, HRMS, HPLC, and in the cases of 2b and 5b, by X-ray analysis. The BODIPYs exhibited low dark toxicity and phototoxicity toward human glioma T98G cells, and their cellular uptake varied significantly, with 5b accumulating the most and 7 the least. All BODIPYs localized mainly within the cell ER. The BODIPYs showed higher permeabilities than lucifer yellow across human hCMEC/D3 brain endothelial cell monolayers as the BBB model. Among this series, 1b showed the highest BBB permeability (Pe = 16.4 × 10-5 cm/s), probably as a result of its lower MW (366 Da) and favorable hydrophobicity (log P = 1.5). The combination of low cytotoxicity, amphiphilicity, high boron content, high cellular uptake, and moderate BBB permeability renders these compounds promising boron delivery agents for the BNCT of brain tumors. [ABSTRACT FROM AUTHOR]

Porphyrins and metalloporphyrins have unique chemical and electronic properties and thus provide useful model structures for studies of nanoscale electronic properties. The rigid planar structures and π-conjugated backbones of porphyrins convey robust electrical characteristics. For our investigations, cobaltacarborane porphyrins were synthesized using a ring-opening zwitterionic reaction to produce isomers with selected arrangements of carborane clusters on each macrocycle. Experiments were designed to investigate how the molecular structure influences the selforganization, surface assembly, and conductive properties of three molecular structures with 2, 4, or 8 cobaltacarborane substituents. Current versus voltage (I-V) spectra for designed cobaltacarborane porphyrins deposited on conductive gold substrates were acquired using conductive probe atomic force microscopy (CP-AFM). Characterizations with CP-AFM provide capabilities for obtaining physical measurements and structural information with unprecedented sensitivity. We found that the morphology of cobaltacarborane porphyrin structures formed on surfaces depends on a complex interplay of factors such as the solvent used for dissolution, the nature of the substrate, and the design of the parent molecule. The conductive properties of cobaltacarborane porphyrins were observed to change according to the arrangement of cobaltacarborane substituents. Specifically, the number and placement of the cobaltacarborane ligands on the porphyrin macrocycle affect the interactions that drive porphyrin self-assembly and crystallization. Interestingly, coulombic staircase I-V profiles were detected for a porphyrin with two cobaltacarborane substituents. [ABSTRACT FROM AUTHOR]

A series of four BODIPYs containing one or two ortho - or para -carborane clusters were synthesized using palladium(0)-catalyzed Suzuki cross-coupling or nucleophilic substitution reactions, at the 2,6- or the 8-positions of halogenated boron dipyrromethenes (BODIPYs). The spectroscopic, structural (including one X-ray) and in vitro BBB permeability of the BODIPYs using hCMEC/D3 brain endothelial cells were investigated. [ABSTRACT FROM AUTHOR]

A series of 14 symmetric ( 1a – g ) and asymmetric ( 2a – g ) BODIPYs bearing two different substituents at the boron center were synthesized in a one-pot reaction from dipyrrins 1 and 2 , respectively, in 14–63% isolated yields. The reaction involves the treatment of dipyrrin with phenylboron dichloride followed by nucleophilic substitution of the chloride group using various nucleophiles, including TBAF, TMSCN, ROH, acetate, and alkoxides. The reactions are completed within 2 h at room temperature. The spectroscopic and 11 B NMR properties of the new BODIPYs were investigated and three crystal structures are presented. [ABSTRACT FROM AUTHOR]

An effective, stepwise methodology for polychlorination of BODIPY using trichloroisocyanuric acid (TCCA) in acetic acid was developed. In this way, selectively substituted di-, tri-, tetra-, and pentachloro-BODIPYs 2-5 were prepared. The pentachloro-BODIPY is shown to undergo regioselective Pd(0)-catalyzed Stille and Suzuki coupling reactions, first at the 8-position followed by the 3,5- and then the 2,6-positions; nucleophilic substitution reactions occur first at the 8- followed by the 3,5-positions, while the 2,6 are unreactive. [ABSTRACT FROM AUTHOR]

A series of boron-disubstituted O-BODIPYs were synthesized, and their structures and spectroscopic properties were investigated using both computational and experimental methods. Three methods were investigated for the preparation of 4,4-dimethoxy-BODIPYs bearing electron-donating or electron-withdrawing 8-aryl groups: method A employs refluxing in the presence of NaOMe/MeOH, method B uses AlCl3 in refluxing dichloromethane followed by addition of methanol as nucleophile, and method C involves activation of the BODIPYs using TMSOTf in refluxing toluene followed by addition of methanol. The yields obtained depend on the method used and the structure of the starting BODIPYs; for example, 1a and 3a were most efficiently prepared using method C (98 and 70%, respectively), while 2a was best prepared by method A (50%). Methods B and C were employed for the synthesis of seven new 4,4-dialkoxy-BODIPYs. 4,4-Dipropargyloxy-BODIPY 1e reacted under Cu(I)-catalyzed alkyne-azide Huisgen cycloaddition conditions to produce 4,4-bis(1,2,3-triazole)-BODIPY 4 in 78% yield. The substitution of the fluorides for alkoxy groups on the BODIPYs had no significant effect on the absorption and emission wavelengths but altered their fluorescence quantum yields. Among this series of dialkoxy-BODIPYs, the 4,4-dipropargyloxy 1e and its corresponding bis(1,2,3-triazole) 4 show the largest quantum yields in toluene and THF, respectively. [ABSTRACT FROM AUTHOR]

A series of five mono-styryl and their corresponding symmetric di-styryl-2,6-diiodo-BODIPYs containing indolyl, pyrrolyl, thienyl or tri(ethylene glycol)phenyl groups were synthesized using Knoevenagel condensations. The yields for the condensation reactions were improved up to 40% using microwave irradiation (90 °C for 1 h at 400 W) due to lower decomposition of BODIPYs upon prolonged heating. The spectroscopic, structural (including the X-ray of a di-styryl-2,6-diiodo-BODIPY) and in vitro properties of the BODIPYs were investigated. The extension of π-conjugation through the 3,5-dimethyls of the known phototoxic 2,6-diiodo-BODIPY 1 produced bathochromic shifts in the absorption and emission spectra, in the order of 63–125 nm for the mono-styryl- and 128–220 nm for the di-styryl-BODIPYs in DMSO. The largest red-shifts were observed for the indolyl-containing BODIPYs while the largest fluorescence quantum yields were observed for the tri(ethyleneglycol)phenylstyryl-BODIPYs. Among this series, only the mono-styryl-BODIPYs were phototoxic (IC 50 = 2–15 μM at 1.5 J/cm 2 ), and were observed to localize preferentially in the cell ER and mitochondria. On the other hand, the di-styryl-BODIPYs were found to have low or no phototoxicity (IC 50 > 100 μM at 1.5 J/cm 2 ). Among this series of compounds BODIPY 2a shows the most promise for application as photosensitizer in PDT. [ABSTRACT FROM AUTHOR]

Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis( p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC's applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm2) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 1012 n/cm2) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37-43 days). © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:962-970, 2015 [ABSTRACT FROM AUTHOR]

A series of tri[(p-carboranylmethylthio)tetrafluorophenyl]porphyrinconjugates of linear and branched polyamines, glucose, arginine, tri(ethyleneglycol), and Tyr-d-Arg-Phe-β-Ala (YRFA) peptide weresynthesized. These conjugates were investigated for their BBB permeabilityin human hCMEC/D3 brain endothelial cells, and their cytotoxicityand uptake were assessed using human glioma T98G cells. For comparisonpurposes, a symmetric tetra[(p-carboranylmethylthio)tetrafluorophenyl]porphyrinwas also synthesized, and its crystal structure was obtained. Allporphyrin conjugates show low dark cytotoxicity (IC50>400 μM) and low phototoxicity (IC50> 100 μMat 1.5 J/cm2) toward T98G cells. All conjugates were efficientlytaken up by T98G cells, particularly the cationic polyamine and arginineconjugates, and were localized in multiple cellular organelles, includingmitochondria and lysosomes. All compounds showed relatively low invitro BBB permeability compared with that of lucifer yellow becauseof their higher molecular weight, hydrophobicity, and tendency foraggregation in solution. Within this series, the branched polyamineand YRFA conjugates showed the highest permeability coefficient, whereasthe glucose conjugate showed the lowest permeability coefficient. [ABSTRACT FROM AUTHOR]

Novel aza-BODIPYs with significant bathochromic shifts were designed and synthesized by installation of strong electron-withdrawing groups on the para-positions of 1,7-phenyls and electron-donating groups on the para-positions of 3,4-phenyls. These dyes show strong NIR fluorescence emissions up to 756 nm, and absorptions up to 720 nm. [ABSTRACT FROM AUTHOR]

Abstract: A series of twenty-two BODIPY compounds were synthesized, containing various meso-phenyl and meso-thienyl groups, and their spectroscopic and structural properties were investigated using both experimental and computational methods. Further functionalization of the BODIPY framework via iodination at the 2,6-pyrrolic positions was explored in order to determine the effect of these heavy atoms on the photophysical and cytotoxicity of the meso-aryl-BODIPYs. BODIPYs bearing meso-thienyl substituents showed the largest red-shifted absorptions and emissions and reduced fluorescence quantum yields. The phototoxicity of the BODIPYs in human carcinoma HEp2 cells depends on both the presence of iodines and the nature of the meso-aryl groups. Six of the eleven 2,6-diiodo-BODIPYs investigated showed at least a sevenfold enhancement in phototoxicity (IC50 =3.5–28μM at 1.5J/cm2) compared with the non-iodinated BODIPYs, while the others showed no cytotoxicity, while their singlet oxygen quantum yields ranged from 0.02 to 0.76. Among the series investigated, BODIPYs 2a and 4a bearing electron-donating meso-dimethoxyphenyl substituents showed the highest phototoxicity and dark/phototoxicity ratio, and are therefore the most promising for application in PDT. [Copyright &y& Elsevier]

5,10,15-Triaryltetrabenzocorroles functionalized with different electron-withdrawing groups on the ß,ß'-fused rings have been prepared by a cross-coupling Heck procedure between octabrominated copper corrole and a terminal alkene bearing electron-withdrawing moieties. The spectroscopic characterization of these complexes showed red-shifted UV-vis absorption bands characterized by a significant band broadening. The same feature was observed in the case of NMR spectra, where low-resolution groups of signals were observed. This behavior derives from a strong tendency of these macrocycles to aggregate in solution, as has been demonstrated by an ¹H NMR study performed on one of these tetrabenzocorroles. The influence of the substituents on the fused benzene ring on the properties of the tetrabenzocorroles was investigated by electrochemistry and spectroelectrochemistry, and comparisons were made between properties of the newly synthesized compounds and those of the tetrabenzocorroles reported earlier in the literature. [ABSTRACT FROM AUTHOR]

Four phthalocyanine (Pc)–peptideconjugatesdesigned to target the epidermal growth factor receptor (EGFR) weresynthesized and evaluated in vitro using four cell lines: human carcinomaA431 and HEp2, human colorectal HT-29, and kidney Vero (negative control)cells. Two peptide ligands for EGFR were investigated: EGFR-L1 and-L2, bearing 6 and 13 amino acid residues, respectively. The peptidesand Pc-conjugates were shown to bind to EGFR usingboth theoretical (Autodock) and experimental (SPR) investigations.The Pc–EGFR-L1 conjugates 5aand 5befficiently targeted EGFR and were internalized, in partdue to their cationic charge, whereas the uncharged Pc–EGFR-L2 conjugates 4band 6apoorlytargeted EGFR maybe due to their low aqueous solubility. All conjugateswere nontoxic (IC50> 100 μM) to HT-29 cells,bothin the dark and upon light activation (1 J/cm2). Intravenous(iv) administration of conjugate 5binto nude mice bearingA431 and HT-29 human tumor xenografts resulted in a near-IR fluorescencesignal at ca. 700 nm, 24 h after administration. Our studies showthat Pc–EGFR-L1 conjugates are promising near-IRfluorescent contrast agents for CRC and potentially other EGFR overexpressingcancers. [ABSTRACT FROM AUTHOR]

A series of low-spin, six-coordinate complexes [Fe(TBzTArP)L2]X (1) and [Fe(TBuTArP)L2]X (2) (X = Cl−, BF4−, or Bu4N+), where the axial ligands (L) are HIm, 1-MeIm, DMAP, 4-MeOPy, 4-MePy, Py, and CN−, were prepared. The electronic structures of these complexes were examined by 1H NMR and electron paramagnetic resonance (EPR) spectroscopy as well as density functional theory (DFT) calculations. In spite of the fact that almost all of the bis(HIm), bis(1-MeIm), and bis(DMAP) complexes reported previously (including 2) adopt the (dxy)2(dxz, dyz)3 ground state, the corresponding complexes of 1 show the (dxz, dyz)4(dxy)1 ground state at ambient temperature. At lower temperature, the electronic ground state of the HIm, 1-MeIm, and DMAP complexes of 1 changes to the common (dxy)2(dxz, dyz)3 ground state. All of the other complexes of 1 and 2 carrying 4-MeOPy, 4-MePy, Py, and CN− maintain the (dxz, dyz)4(dxy)1 ground state in the NMR temperature range, i.e., 298−173 K. The EPR spectra taken at 4.2 K are fully consistent with the NMR results because the HIm and 1-MeIm complexes of 1 and 2 adopt the (dxy)2(dxz, dyz)3 ground state, as revealed by the rhombic-type spectra. The DMAP complex of 1 exists as a mixture of two electron-configurational isomers. All of the other complexes adopt the (dxz, dyz)4(dxy)1 ground state, as revealed by the axial-type spectra. Among the complexes adopting the (dxz, dyz)4(dxy)1 ground state, the energy gap between the dxy and dπ orbitals in 1 is always larger than that of the corresponding complex of 2. Thus, it is clear that the benzoannelation of the porphyrin ring stabilizes the (dxz, dyz)4(dxy)1 ground state. The DFT calculation of the bis(Py) complex of analogous iron(III) porphyrinate, [Fe(TPTBzP)(Py)2]+, suggests that the (dxz, dyz)4(dxy)1 state is more stable than the (dxy)2(dxz, dyz)3 state in both ruffled and saddled conformations. The lowest-energy states in the two conformers are so close in energy that their ordering is reversed depending on the calculation methods applied. On the basis of the spectroscopic and theoretical results, we concluded that 1, having 4-MeOPy, 4-MePy, and Py as axial ligands, exists as an equilibrium mixture of saddled and ruffled isomers both of which adopt the (dxz, dyz)4(dxy)1 ground state. The stability of the (dxz, dyz)4(dxy)1 ground state is ascribed to the strong bonding interaction between the iron dxy and porphyrin a1u orbitals in the saddled conformer caused by the high energy of the a1u highest occupied molecular orbital in TBzTArP. Similarly, a bonding interaction occurs between the dxy and a2u orbitals in the ruffled conformer. In addition, the bonding interaction of the dπ orbitals with the low-lying lowest unoccupied molecular orbital, which is an inherent characteristic of TBzTArP, can also contribute to stabilization of the (dxz, dyz)4(dxy)1 ground state. [ABSTRACT FROM AUTHOR]

Copper ion is a biochemically essential yet toxic metal ion, connected to serious neurodegenerative diseases, and also has been identified as an environmental pollutant. For the effective detection of Cu2+in biological and environmental systems, we have developed a new membrane-permeable Cu2+-selective water-soluble BODIPY 1, which was synthesized by nucleophilic disubstitution of novel 3,5-diiodo-BODIPY 4with N,N-bis(2-hydroxyethyl)amines. BODIPY 1shows a highly sensitive and selective fluorescence response to Cu2+in aqueous solution. Fluorescence image experiments establish that 1can be used to monitor intracellular Cu2+within living cells. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis and photophysical properties of a new series of zinc(II) phthalocyanines (ZnPcs) bearing multiple hydroxy and tert-butyl groups are reported. The X-ray structures of two phthalonitriles and one ZnPc are presented. All hydroxy-substituted ZnPcs show low fluorescence quantum yields in DMSO and complete fluorescence quenching in aqueous solutions, but high singlet oxygen quantum yields in DMSO (0.2–0.7). Our results suggest that the tetra- and octa-hydroxy ZnPcs might find application as photosensitizers in the PDT treatment of cancer. [Copyright &y& Elsevier]

Abstract: A series of carboranylporphyrins containing either amine or phosphonic acid functionalities and two to six closo-carborane clusters have been synthesized via a [2+2] condensation of a dimethylamino- or diethylphosphonate-substituted dipyrromethane with a dicarboranylmethyl-benzaldehyde. The X-ray structures of four key reaction intermediates (1, 2, 3, and 4a) and of two target porphyrins, the diphosphonate ester- and the diamino-tetracarboranylporphyrins 5b and 6a, are presented and discussed. In vitro studies using human carcinoma HEp2 and human glioblastoma T98G cells show that these porphyrins are non-toxic in the dark up to 100μM concentrations, and that a tetracarboranylporphyrin bearing two quaternary ammonium groups is the most efficiently taken up by cells at short times (up to 8h), followed by a dicarboranylporphyrin bearing three phosphonic acid substituents. All carboranylporphyrins delivered therapeutic amounts of boron to T98G cells and localized mainly within the cell lysosomes. [Copyright &y& Elsevier]

Abstract: Six new functionalized oxacalix[4]arene porphyrins have been synthesized via a high-yielding ‘3+1’ condensation between meso-(3,5-dihydroxyphenyl)triphenylporphyrin and readily available new fluorodinitrobenzene-containing trimers. The X-ray structure of one linear trimer is presented. The synthesis of a porphyrin containing two oxacalix[4]arene moieties is also reported using a similar strategy. 1H NMR data and computer calculations using the AM1 semiempirical method incorporated into the Spartan program indicate that the oxacalix[4]arene porphyrins adopt 1,3-alternating conformations. The photophysical properties of the oxacalix[4]arene porphyrins were investigated. [Copyright &y& Elsevier]

β,β′-Fused monoruthenocenylporphyrins, Cp*Ru(III)[1,2-[M(II)-5, 10,1 5,20-tetrakis(3,5-di-tert-butylphenyl)-porphyrinato]-3-methyl-cyclopentadienide] (M = Ni (20), Cu (21), Zn (22)), and bisferrocenoporphyrins, Fe(II) bis[1,2-[M(II)-5,10,15,20-tetraphenylporphyrinato]-3-methyl-cyclopentadienide] (M Ni (24), Cu (25), Zn (26)), were synthesized and characterized. A novel synthetic approach to β,β′-fused porphyrins through Pd(0)-catalyzed [3 + 2] cycloaddition was implemented in this work. UV-vis spectra of these compounds show largely broadened and red-shifted bands (relative to their precursors) indicating potential electronic communication between the attached organometallic moiety and the porphyrin core. The electrochemistry of these molecules suggests significant electronic interactions between the metallocene and metalloporphyrin in molecules 20 and 24. The crystal structure of the bisferrocenoporphyrin 26, Fe(II) bis[1,2-[Zn(II)-5,10,1 5,20-tetraphenylporphyrinato]-3-methyl-cyclopentadienide], was determined: {Cp2Fe[ZnTPP(THF)]2}{Cp2Fe[ZnTPP(THF)ZnTPP(MeOH)]}•3MeOH•6THF, M = 3804.35, monoclinic, space group P21/c, a = 33.327(5) Å, b = 19.145(3) Å, c 29.603(5) Å, β = 106.309(2)°, V = 18128(5) ų, z = 4. In this molecule, one porphyrin ring is rotated by about 72° with respect to the other in the 5-fold axis of the Cp ring. [ABSTRACT FROM AUTHOR]

Abstract: The syntheses of closo- and nido-carboranylchlorins 4 and 5 from a known carboranylporphyrin are described. Water-soluble nido-carboranylporphyrin 5 was found to have very low dark cytotoxicity (IC50 >500μM using a MTT-based assay) but to be toxic in the presence of red light (IC50 =80μM at 0.55J/cm2 light dose). Under the same experimental conditions, carboranylchlorin 5 was taken up by human glioma T98G cells to a significantly higher extent than chlorin e6, a chlorophyll degradation product. The preferred sites of subcellular localization of carboranylchlorin 5 were found to be the cell lysosomes. Our results suggest that carboranylchlorin 5 is a promising new dual sensitizer for the PDT and BNCT treatment of tumors. [Copyright &y& Elsevier]

Abstract: A water-soluble nido-carboranyl-tetrabenzoporphyrin has been synthesized in 43% overall yield, by condensation of butanopyrrole with a carboranylbenzaldehyde, followed by metal insertion, oxidation, demetallation and deboronation reactions. This compound accumulated within human glioblastoma T98G cells to a significant higher extent than a structurally related nido-carboranylporphyrin, and localized preferentially in the cell lysosomes. Animal toxicity studies using male and female BALB/c mice revealed that both compounds are non-toxic even at a dose of 160mg/kg, administered intraperitoneally as a single injection at a concentration of 4mg/mL. It is concluded that the tetra(carboranylphenyl)-tetrabenzoporphyrin is a promising new sensitizer for the treatment of malignant tumors. [Copyright &y& Elsevier]