Chiral Supramolecular Organogel Constructed Using Riboflavin and Melamine: Its Application in Photo-Catalyzed Colorimetric Chiral Sensing and Enantioselective Adsorption.

The synthesis of a chiral supramolecular organogel via the hierarchical helical self-assembly of optically active riboflavin and melamine derivatives is described herein. Owing to the photocatalysis of riboflavin and the supramolecular chirality induced in the helically stacked riboflavin/melamine complex, the gel is observed to act as a light-stimulated chiral sensor of optically active alcohols by detecting the change in color from yellow to green. The gel also served as an efficient chiral adsorbent, enabling optical resolution of a racemic compound with high chiral recognition ability.

A Photochemical Study of Photo-Induced Electron Transfer from DNAs to a Cationic Phthalocyanine Derivative.

Water-soluble cationic gallium(III)-Pc complex (GaPc) is capable of photogenerating ROSs but does not exhibit photocytotoxicity in vivo. GaPc binds selectively, through a π-π stacking interaction, to the 5'-terminal G-quartet of a G-quadruplex DNA. The photo-excited state of GaPc of the complex is effectively quenched through electron transfer (ET) from the ground state of DNA guanine (G) bases to the photo-excited state of GaPc (ET(G-GaPc)). Hence the loss of the photocytotoxicity of GaPc in vivo is most likely to be due to the effective quenching of its photo-excited state through ET(G-GaPc). In this study, we investigated the photochemical properties of GaPc in the presence of duplex DNAs formed from a series of sequences to elucidate the nature of ET(G-GaPc). We found that ET(G-GaPc) is allowed in electrostatic complexes between GaPc and G-containing duplex DNAs and that the rate of ET(G-GaPc) (kET(G-GaPc)) can be reasonably interpreted in terms of the distance between Pc moiety of GaPc and DNA G base in the complex. We also found that the quantum yields of singlet oxygen (1O2) generation (ΦΔs) determined for the GaPc-duplex DNA complexes were similar to the value reported for free GaPc (Fujishiro R, Sonoyama H, Ide Y, et al (2019) J Inorg Biochem 192:7-16), indicating that ET(G-GaPc) in the complex is rather limited. These results clearly demonstrated that photocytotoxicity of GaPc is crucially affected by ET(G-GaPc). Thus elucidation of interaction of a photosensitizer with biomolecules, i.e., an initial process in PDT, would be helpful to understand its subsequent photochemical processes.

Iron(III) 5,15-Diazaporphyrin Catalysts for the Direct Oxidation of C(sp3)-H Bonds.

5,15-Diazaporphyrins are porphyrin analogues with imine-type sp2-hybridized nitrogen atoms at the meso-positions. Even though these compounds are more electron-deficient than regular porphyrins, the use of iron diazaporphyrins as catalysts has not been reported. Herein, we disclose the synthesis, structure, and electronic properties of iron(III) 5,15-diazaporphyrins. We evaluate their structures and electronic natures by X-ray analysis and electrochemical analyses. We also demonstrate that chloroiron(III) 5,15-diazaporphyrins exhibit high catalytic activity in the direct oxidation of alkanes due to their intrinsic electron-deficient nature. On the basis of stoichiometric reactions of iron(III) diazaporphyrin with iodosylbenzene as an oxidant, it was possible to demonstrate the existence of an iodosylbenzene-iron diazaporphyrin adduct reaction intermediate that serves as a reservoir to generate oxo-iron species.

5,5,15,15-Tetraoxo-5,15-Dithiaporphyrin as a Highly Electron-Deficient Porphyrinic Ligand.

Oxidation of 5,15-dithiaporphyrin with meta-chloroperbenzoic acid afforded the corresponding S,S-tetraoxide in good yield. The resultant 5,5,15,15-tetraoxo-5,15-dithiaporphyrin exhibited the highly electron-deficient nature as elucidated by the electrochemical analysis and theoretical calculations. Treatment of tetraoxodithiaporphyrin with zinc(II) acetate and nickel(II) acetate provided the corresponding metal complexes efficiently. Owing to its enhanced Lewis acidity of the metal center by the electron-deficient ligand, the nickel complex underwent facile axial ligation to form pentacoordinate and hexacoordinate high-spin (S=1) complexes in solution and solid, respectively. The binding constant of pyridine to the NiII center was significantly higher than those of conventional porphyrin NiII complexes. Temperature-dependent magnetic susceptibility measurements of the high-spin NiII complex revealed the presence of weak ferromagnetic interactions.

Coordination-Induced Spin-State Switching of an Aminyl-Radical-Bridged Nickel(II) Porphyrin Dimer between Doublet and Sextet States.

A bis(NiII -porphyrinyl)aminyl radical with meso-C6 F5 groups was prepared as a spin-delocalized stable aminyl radical with a doublet spin state. Upon addition of pyridine, both NiII centers became hexacoordinated by accepting two axial pyridines, which triggered a spin-state change of the NiII centers from diamagnetic (S=0) to paramagnetic (S=1). The resulting high-spin NiII centers interact with the aminyl radical ferromagnetically to give rise to an overall sextet state (S=5/2). Importantly, this coordination-induced spin-state switching can be conducted in a reversible manner, in that washing of the high-spin radical with aqueous hydrochloric acid regenerates the original doublet radical in good yield.

Benzonorcorrole NiII Complexes: Enhancement of Paratropic Ring Current and Singlet Diradical Character by Benzo-Fusion.

Fused benzene rings to antiaromatic compounds generally improve their stability but attenuate their antiaromaticity. The opposite case is now reported. NiII benzonorcorroles were synthesized and the effect of benzo-fusion on the antiaromaticity was elucidated. The benzo-fusion resulted in significant decrease of the HOMO-LUMO gaps and enhancement of the paratropic ring current effect. Furthermore, the introduction of the benzo groups induced singlet diradical character in the antiaromatic porphyrinoid.

Benzoannelation stabilizes the d(xy)1 state of low-spin iron(III) porphyrinates.

A series of low-spin, six-coordinate complexes [Fe(TBzTArP)L(2)]X (1) and [Fe(TBuTArP)L(2)]X (2) (X = Cl(-), BF(4)(-), or Bu(4)N(+)), 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 (1)H 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 (d(xy))(2)(d(xz), d(yz))(3) ground state, the corresponding complexes of 1 show the (d(xz), d(yz))(4)(d(xy))(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 (d(xy))(2)(d(xz), d(yz))(3) ground state. All of the other complexes of 1 and 2 carrying 4-MeOPy, 4-MePy, Py, and CN(-) maintain the (d(xz), d(yz))(4)(d(xy))(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 (d(xy))(2)(d(xz), d(yz))(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 (d(xz), d(yz))(4)(d(xy))(1) ground state, as revealed by the axial-type spectra. Among the complexes adopting the (d(xz), d(yz))(4)(d(xy))(1) ground state, the energy gap between the d(xy) and d(π) 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 (d(xz), d(yz))(4)(d(xy))(1) ground state. The DFT calculation of the bis(Py) complex of analogous iron(III) porphyrinate, [Fe(TPTBzP)(Py)(2)](+), suggests that the (d(xz), d(yz))(4)(d(xy))(1) state is more stable than the (d(xy))(2)(d(xz), d(yz))(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 (d(xz), d(yz))(4)(d(xy))(1) ground state. The stability of the (d(xz), d(yz))(4)(d(xy))(1) ground state is ascribed to the strong bonding interaction between the iron d(xy) and porphyrin a(1u) orbitals in the saddled conformer caused by the high energy of the a(1u) highest occupied molecular orbital in TBzTArP. Similarly, a bonding interaction occurs between the d(xy) and a(2u) orbitals in the ruffled conformer. In addition, the bonding interaction of the d(π) orbitals with the low-lying lowest unoccupied molecular orbital, which is an inherent characteristic of TBzTArP, can also contribute to stabilization of the (d(xz), d(yz))(4)(d(xy))(1) ground state.

Stepwise binding of a cationic phthalocyanine derivative to an all parallel-stranded tetrameric G-quadruplex DNA.

Interaction between an Ga(III) phthalocyanine (Pc) derivative bearing eight N-methylpyridinium groups at peripheral ß-positions (2,3,6,7,10,11,14,15-octakis-[N-methyl-(4-methylpyridinium-3-yloxy)phthalocyaninato] chloro gallium(III) iodide (GaPc)) and an all parallel-stranded tetrameric G-quadruplex formed from a heptanucleotide d(TTAGGGT) ([d(TTAGGGT)]4) has been investigated to elucidate the molecular recognition of G-quadruplex DNA by the Pc derivative, which provides a useful insight as to the design of G-quadruplex ligands suitable for various in vitro and in vivo applications. We found that GaPc binds to the A3G4 and G6T7 steps of [d(TTAGGGT)]4, with binding constants of (21 ± 2) × 106 and (0.09 ± 0.06) × 106 M-1, respectively, to form a 2:1 complex. Obviously, upon the binding of GaPc to each of the sites, the π-π stacking and electrostatic interactions of the Pc moiety and positively-charged side chains of GaPc with a G-quartet and the negatively-charged phosphate groups in nearby phosphodiester bonds of the DNA, respectively, are major driving forces for the complexation. Considering the similarity in the local structural environment between the A3G4 and G6T7 steps of [d(TTAGGGT)]4, the remarkably large difference in the GaPc-binding affinity between them is most likely accounted for by the effect of the polarity of the GaPc-binding site on the intermolecular electrostatic interaction. This finding provides valuable insights as to the design of Pc derivatives as G-quadruplex ligands.

A Cationic Gallium Phthalocyanine Inhibits Amyloid ß Peptide Fibril Formation.

BACKGROUND: Amyloid ß (Aß) peptide deposition is considered as the main cause of Alzheimer's disease (AD). Previously, we have shown that a Zn containing neutral phthalocyanine (Zn-Pc) inhibits Aß fibril formation. OBJECTIVE: The objective of this study is to investigate the effects of a cationic gallium containing Pc (GaCl-Pc) on Aß fibril formation process. METHODS AND RESULT: Aß fibril formation was induced by incubating synthetic Aß peptides in a fibril forming buffer, and the amount of fibril was evaluated by ThT fluorescence assay. GaCl-Pc dosedependently inhibited both Aß1-40 and Aß1-42 fibril formation. It mainly inhibited the elongation phase of Aß1-42 fibril formation kinetics, but not the lag phase. Western blotting results showed that it did not inhibit its oligomerization process, rather increased it. Additionally, GaCl-Pc destabilized preformed Aß1- 42 fibrils dose-dependently in vitro condition, and decreased Aß levels in the brain slice culture of APP transgenic AD model mice (J20 strain). Near-infrared scanning results showed that GaCl-Pc had the ability to bind to Aß1-42. MTT assay demonstrated that GaCl-Pc did not have toxicity towards a neuronal cell line (A1) in culture rather, showed protective effects on Aß-induced toxicity. Moreover, it dosedependently decreased Aß-induced reactive oxygen species levels in A1 culture. CONCLUSION: Thus, our result demonstrated that GaCl-Pc decreased Aß aggregation and destabilized the preformed fibrils. Since cationic molecules show a better ability to cross the blood-brain barrier, cationic GaCl-Pc could be important for the therapy of AD.

Bis-copper(II) Complex of Triply-linked Corrole Dimer and Its Dication.

Copper complexes of corroles have recently been a subject of keen interest due to their ligand non-innocent character and unique redox properties. Here we investigated bis-copper complex of a triply-linked corrole dimer that serves as a pair of divalent metal ligands but can be reduced to a pair of trivalent metal ligands. Reaction of triply-linked corrole dimer 2 with Cu(acac)2 (acac=acetylacetonate) gave bis-copper(II) complex 2Cu as a highly planar molecule with a mean-plane deviation value of 0.020 Å, where the two copper ions were revealed to be divalent by ESR, SQUID, and XPS methods. Oxidation of 2Cu with two equivalents of AgBF4 gave complex 3Cu, which was characterized as a bis-copper(II) complex of a dicationic triply-linked corrole dimer not as the corresponding bis-copper(III) complex. In accord with this assignment, the structural parameters around the copper ions were revealed to be quite similar for 2Cu and 3Cu. Importantly, the magnetic spin-spin interaction differs depending on the redox-state of the ligand, being weak ferromagnetic in 2Cu and antiferromagnetic in 3Cu.

Synthesis, photodynamic activities, and cytotoxicity of new water-soluble cationic gallium(III) and zinc(II) phthalocyanines.

The cationic Ga(III) and Zn(II) phthalocyanines carrying N-methyl-pyridinium groups at eight peripheral ß-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 (1O2), and cytotoxicity of these complexes have been investigated. The absolute quantum yields (ΦΔabsolute) 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).

Electronic structure of six-coordinate iron(III) monoazaporphyrins.

The electronic structures of six-coordinate iron(III) octaethylmonoazaporphyrins, [Fe(MAzP)L 2] (+/-) ( 1), have been examined by means of (1)H NMR and EPR spectroscopy to reveal the effect of meso-nitrogen in the porphyrin ring. The complexes carrying axial ligands with strong field strengths such as 1-MeIm, DMAP, CN (-), and (t)BuNC adopt the low-spin state with the (d xy ) (2)(d xz , d yz ) (3) ground state in a wide temperature range where the (1)H NMR and EPR spectra are taken. In contrast, the complexes with much weaker axial ligands, such as 4-CNPy and 3,5-Cl 2Py, exhibit the spin transition from the mainly S = 3/2 at 298 K to the S = 1/2 with the (d xy ) (2)(d xz , d yz ) (3) ground state at 4 K. Only the THF complex has maintained the S = 3/2 throughout the temperature range examined. Thus, the electronic structures of 1 resemble those of the corresponding iron(III) octaethylporphyrins, [Fe(OEP)L 2] (+/-) ( 2). A couple of differences have been observed, however, in the electronic structures of 1 and 2. One of the differences is the electronic ground state in low-spin bis( (t)BuNC) complexes. While [Fe(OEP)( (t)BuNC) 2] (+) adopts the (d xz , d yz ) (4)(d xy ) (1) ground state, like most of the bis( (t)BuNC) complexes reported previously, [Fe(MAzP)( (t)BuNC) 2] (+) has shown the (d xy ) (2)(d xz , d yz ) (3) ground state. Another difference is the spin state of the bis(3,5-Cl 2Py) complexes. While [Fe(OEP)(3,5-Cl 2Py) 2] (+) has maintained the mixed S = 3/2 and 5/2 spin state from 298 to 4 K, [Fe(MAzP)(3,5-Cl 2Py) 2] (+) has shown the spin transition mentioned above. These differences have been ascribed to the narrower N4 cavity and the presence of lower-lying pi* orbital in MAzP as compared with OEP.

Nickel (II) pyrrocorphin: Enhanced binding ability in a highly reduced porphyrin complex.

Pyrrocorphin is an air-sensitive porphyrinoid with a highly reduced hexahydroporphyrin core. In contrast, pyrrolidine-fused pyrrocorphin (Pyr) obtained by successive 1,3-dipolar cycloaddition reactions of azomethine ylide to 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin is less air-sensitive. In order to reveal the effect of highly reduced porphyrin rings on the physicochemical properties of their metal complexes, we have prepared diamagnetic (S=0) Ni(II) complex Ni(II)(Pyr). The addition of excess pyridine (Py) to the toluene solution of Ni(II)(Pyr) yielded five-coordinate Ni(II)(Pyr)(Py), which was then completely converted to six-coordinate paramagnetic (S=1) Ni(II)(Pyr)(Py)2. The latter was characterized by UV-Vis, 1H NMR, CV, SQUID, and X-ray crystallography as well as DFT calculations. As compared with analogous complexes of porphyrin (Por), chlorin (Chl), and isobacteriochlorin (Iso) reported by Herges and co-workers (R. Herges et al., Inorg. Chem. 2015), Ni(II)(Pyr)(Py)2 has longer equatorial NiN and shorter axial NiN bonds. The CV study has shown a large decrease in HOMO-LUMO gap as the reduction of porphyrin ring proceeds, which has further been confirmed by UV-Vis and DFT calculation. Titration studies using 1H NMR and UV-Vis have shown that the first binding constant of pyridine toward Ni(II)(Pyr) is ca. 4 times as large as that of Ni(II)(Iso) and ca 230 times as large as that of Ni(II)(Por). Thus, we have concluded that the binding constant of pyridine to Ni(II) porphyrinoid increases by the following order: Por

Analysis of Disperse Dyes Using Liquid Chromatography/Linear Ion Trap Mass Spectrometry (LC/LIT-MSn) and Database Construction.

Liquid chromatography/linear ion trap mass spectrometry (LC/LIT-MS(n)) was used to construct a database of disperse dyes. Fifty-three standard dyes were subjected to LC/LIT-MS(n) and characterized based on their mass spectra (MS, MS(2), and MS(3)), values of λmax (maximum absorption wavelength in the UV-visible spectrum), and retention times. The results demonstrate that it is possible to reliably identify coexisting dyes that cannot be separated by LC or detected by diode array detection due to their low molecular absorption coefficients. In addition, the by-products included in the standard dyes were found to provide important information for the identification and discrimination of dyestuffs synthesized using different processes. The confirmation of the effectiveness of LC/LIT-MS(n) analysis in detecting small amounts of disperse dyes in this study shows its potential for use in the discrimination of dyed fibers obtained at crime scenes.

Spin-crossover between high-spin (S = 5/2) and low-spin (S = 1/2) states in six-coordinate iron(iii) porphyrin complexes having two pyridine-N oxide derivatives.

In contrast to the general tendency that six coordinate iron(iii) porphyrin complexes with neutral oxygen ligands adopt a high-spin state in a wide range of temperature, some complexes with substituted pyridine N-oxides have exhibited spin-crossover from high-spin to low-spin states with decreasing temperature both in solution and in the solid state.

An unprecedented up-field shift in the 13C NMR spectrum of the carboxyl carbons of the lantern-type dinuclear complex TBA[Ru2(O2CCH3)4Cl2] (TBA+ = tetra(n-butyl)ammonium cation).

A large up-field shift (-763 ppm) has been observed for the carboxyl carbons of the dichlorido complex TBA[Ru(2)(O(2)CCH(3))(4)Cl(2)] (TBA(+) = tetra(n-butyl)ammonium cation) in the (13)C NMR spectrum (CD(2)Cl(2) at 25 °C). The DFT calculations showed spin delocalization from the paramagnetic Ru(2)(5+) core to the ligands, in agreement with the large up-field shift.

Effects of a nonplanar porphyrin rings on the spin-spin interactions in low-spin ferric porphyrin radical cationst.

Low-spin ferric porphyrin radical cations formed by the oxidation of chloro(meso-tetraalkylporphyrinato)iron(III) followed by the addition of bulky 2-methylimidazole show antiferromagnetic coupling, which is interpreted in terms of the interaction between porphyrin a2u and iron d(xy), orbitals caused by the S4 ruffling of the porphyrin core.

Chemical shift of meso-carbon: a powerful probe to determine the coordination structure and electron configuration of ferric porphyrin complexes.

The meso-13C chemical shifts have been revealed to serve a powerful probe to determine the coordination structure and electron configuration of ferric porphyrin complexes.

Highly saddle shaped (porphyrinato)iron(III) iodide with a pure intermediate spin state.

Combined analyses using NMR, EPR and Mössbauer spectroscopy as well as SQUID magnetometry have revealed that highly saddle shaped Fe(OETPP)I adopts an essentially pure intermediate spin state in spite of the coordination of an iodide ligand.

High-Spin (meso-Tetraalkylporphyrinato)iron(III) Complexes As Studied by X-ray Crystallography, EPR, and Dynamic NMR Spectroscopies.

1H NMR spectra of a series of high-spin (meso-tetraalkylporphyrinato)iron(III) chlorides, [Fe(TRP)Cl] where R = Me, Et, Pr, or (i)Pr, have been measured at various temperatures in CD(2)Cl(2) solution. In the case of the Et, Pr, and (i)Pr complexes, either the methyl or the methylene signal split into two signals with equal integral intensities at low temperature. In contrast, the Me complex did not show any splitting even at -100 degrees C. The results have been ascribed to the hindered rotation of the meso-alkyl groups about C(meso)-C(alpha) bonds. The activation free energies for rotation have been determined as 8.0 (-72 degrees C), 8.5 (-60 degrees C), and 8.9 (-62 degrees C) kcal.mol(-1) for the Et, Pr, and (i)Pr complexes, respectively, at coalescence temperatures given in parentheses. The small activation free energy for rotation of the isopropyl groups observed in the present system is explained in terms of the nonplanarity of the porphyrin ring, which has been verified both by the X-ray crystallographic analysis and by the EPR spectrum taken in a frozen CH(2)Cl(2)-toluene solution. The success in observing the hindered rotation of less bulky primary alkyl groups such as ethyl and propyl groups at an easily accessible temperature range is attributed to the large difference in chemical shifts of the mutually exchanging protons, ca. 3500 Hz in the case of the Et complex, caused by the paramagnetism of the five-coordinated ferric porphyrin complexes.