Published papers

A novel purely organic radical, 5-methoxy-2,2-diphenyl-1,2-dihydroquinoline N -oxyl ( 2 ), has been synthesized and structurally characterized in order to examine the substituent effect on the known derivative, 2,2-diphenyl-1,2-dihydroquinoline N -oxyl ( 1 ). Based on SQUID measurement, 2 exhibited a ferromagnetic interaction obeying the Bleaney–Bowers equation with 2 J = +17 cm−1. X-ray analysis revealed that the 5-methoxy substitution induces an offset π-stacking, resulting in ferromagnetic interactions.

Two aromatic nitroxyl radical derivatives of 2,2-diphenyl-1,2-dihydroquinoline N-oxyl (1), namely, 5-[2-(trimethylsilyl)ethynyl]-2,2-diphenyl-1,2-dihydroquinoline N-oxyl (2) and 5-ethynyl-2,2-diphenyl-1,2-dihydroquinoline N-oxyl (3), were synthesized, and their magneto-structural correlation was described in connection with their assembled structures. Single-crystal XRD analysis of 3 revealed a hydrogen bond between the oxygen atom in the nitroxyl group and the terminal hydrogen atom of the ethynyl group with dO⋯(H)C = 3.099(5) Å. SQUID measurements revealed that 3 follows a 1D antiferromagnetic chain model with J = −10.4 cm−1. In contrast, a slight increase in the χMT value to 0.44 emu K mol−1 was observed in 2, with a decreasing temperature indicating the presence of a weak intermolecular ferromagnetic interaction. These magnetic behaviors differ from that of the unsubstituted radical 1.

The compound 5,12-diacetyl-5,12-dihydroquinoxalino[2,3-b]quinoxaline 1a and its derivatives were prepared, and their solid and solution state spectroscopic properties were studied; 1a shows stronger fluorescence in solution than in the solid state due to aggregation caused by self-quenching. Phenyl or alkoxy substituted derivatives 1b–d show solid state fluorescence with moderate quantum yields of about Φ = 0.12~0.15, although these are 0.01~0.07 in solution. The spectroscopic properties of alkoxy substituted derivatives were hardly changed compared to 1a and 1b, although 1a and 1b have similar absorption and fluorescence maxima in solution and in the solid state. DFT calculations indicate that orbital switching occurs between HOMO and HOMO-1 and HOMO-2 due to orbital interactions with introduced substituents. Crystal structure analysis revealed that the molecules have bent structures around tertiary nitrogen atoms and form a characteristic dimeric structure.

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim A unique superparamagnetic-like behavior and a large “positive magneto-LC effect” were observed in the solid phases and the hexagonal columnar (Col h ) liquid crystalline (LC) phase, respectively, of novel achiral non-π-delocalized nitroxide diradical compounds (R,S)-1, which showed polymorphism in the solid phases (solids I and II). The SQUID magnetization measurement revealed that (1) (R,S)-1 containing a small amount of racemic diastereomers (R*,R*)-1 possessed an unusual and large temperature-independent magnetic susceptibility (χ TIM >0) component in the original nanocrystalline solid I that was responsible for the observed superparamagnetic-like behavior under low magnetic fields and did not arise from the contamination by extrinsic magnetic metal or metal ion impurities, besides ordinary temperature-dependent paramagnetic susceptibility (χ para >0) and temperature-independent diamagnetic susceptibility (χ dia <0) components, (2) a large increase in molar magnetic susceptibility (χ M ) (positive magneto-LC effect) that occurred at the solid I-to-liquid crystal transition upon heating was preserved as an additional χ TIM increase in the resulting polymorphic nanocrystalline solid II by cooling, and (3) such unique magnetic phenomena were induced by thermal processing for (R,S)-1 or by adding a small amount of (R*,R*)-1 to (R,S)-1 as the impurity.

New cyano-substituted 3-tert-butylbenzotriazinyls, 7CN and 6CN, were synthesized and their spectroscopic properties and magneto-structural correlation were investigated. The radical 7CN formed a 1D columnar structure and displayed an antiferromagnetic interaction along the column (J = -15.8 cm^-1). The 6-cyano substituted radical 6CN also formed a 1D columnar structure and exhibited a reversible spin transition at ca. 284 K in the range of 6 K. The molecular arrangements in the high-temperature phase (300 K) and low-temperature phase (263 K) were evaluated by X-ray crystallographic analysis and the molecules slightly rotated while remaining in the 1D columnar structure, resulting in a phase transition. The spin transition behaviour was caused by the structural phase transition, which was consistent with the DSC and computational studies.

Three hetero-biradical derivatives, with the structure of a back-to-back connected benzotriazinyl and tetramethyl or tetraethylisoindoline N-oxyl sharing a common benzo ring, 1-tBu, 1-Ph, and 2-tBu, were synthesized and characterized by single-crystal X-ray analyses, variable-temperature magnetic susceptibility studies, and DFT calculations. Although these radical derivatives form a columnar or chained assembly in the solid state, magnetic measurements of diluted samples in the polymer matrices and computational result simply that the magnetic properties of the polycrystalline sample can be explained by a two-spin system with an intramolecular antiferromagnetic interaction. The moderately strong intramolecular antiferromagnetic interactions can be interpreted by a through-bond interaction through the nonconjugated framework and/or through-space interactions based on molecular orbital theory. The strong distance dependency between the N-O spin site and vinylic carbon atoms indicates that the orbital interaction plays an important role in the intramolecular magnetic interaction.

A nitronyl nitroxide derivative, 2-phenylethynyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxyl-3-oxide (1), and two verdazyl derivatives carrying a phenylacetylene unit, 1,5-diphenyl-3-phenylethynyl-6-oxo-1,2,4,5-tetrazin-2-yl (2) and 1,5-diisopropyl-3-phenylethynyl-6-oxo-1,2,4,5-tetrazin-2-yl (3), were synthesized and their packing structures were studied by X-ray crystallographic analysis and magnetically characterized in the solid state. While 1 and 3 had an isolated doublet spin state, 2 formed an antiferromagnetically coupled pair (2J/kB = −118 K). Density functional theory (DFT) calculations reveal that the spin density polarized in the phenyl group decreases as the dihedral angle between the phenyl ring and radical plane increases.

The magneto‐structural correlation of hetero biradical derivatives containing a 2,2,5,5‐tetramethylpyrrolin‐1‐yloxyl unit as a localized spin center and a verdazyl or nitronyl nitroxide radical is reported. The magnetic susceptibility measurement revealed that the verdazyl attached biradical 1 exhibits ferromagnetic interaction, whereas antiferromagnetic interaction is observed for nitronyl nitroxide attached biradical 2. An EPR study in toluene glass matrix suggests that both 1 and 2 have a ground triplet state. DFT calculations predict that there is intramolecular ferromagnetic interaction for both biradicals. The computation also suggests that the intramolecular magnetic interaction is weaker with larger dihedral angle between pyrroline ring and verdazyl ring/O−N−C−N−O plane of nitronyl nitroxide. The computations of model compounds 3 and 4 suggest that spin polarization on vinylic moiety without distribution of SOMO might be an essential condition for the intramolecular ferromagnetic interaction.

4-Arylethynyl-5-fluorobenzoyl-1-methyl-1H-imidazoles exhibited self-recovering mechanofluorochromism and formed a glass state. Although the solid sampleof the anisyl-substituted 1a and dimethoxyphenyl-substituted 1b exhibited no and blue f luorescence, respectively, they exhibited bluish-green fluorescence after grinding. These compounds recovered the color of their fluorescence after approximately 20s and after 20h, respectively. Both compounds exhibited non-crystalline samples after melting and rapid cooling to room temperature. Based on thermal analysis, it was found 1a and 1b were supercooling liquid and glass, respectively, at room temperature. Both non-crystalline samples exhibited fluorescence at a wavelength longer than that of the solid state. DFT calculations indicated that the bluish-green fluorescence of the ground and noncrystalline samples was derived from the twisted intramolecular charge transfer excitation state.

High-spin organic tetraradicals with significant intramolecular exchange interactions have high potential for advanced technological applications and fundamental research, but those synthesized to date possess limited stability and processability. In this work, we have designed a tetraradical based on the Blatter's radical and nitronyl nitroxide radical moieties and successfully synthesized it by using the palladium-catalyzed cross-coupling reaction of a triiodo-derivative of the 1,2,4-benzotriazinyl radical with gold(I) nitronyl nitroxide-2-ide complex in the presence of a newly developed efficient catalytic system. The molecular and crystal structure of the tetraradical was confirmed by X-ray diffraction analysis. The tetraradical possesses good thermal stability with decomposition onset at ∼150 °C under an inert atmosphere and exhibits reversible redox waves at −0.54 and 0.45 V versus Ag/AgCl. The magnetic properties of the tetraradical were characterized by SQUID magnetometry of polycrystalline powders and EPR spectroscopy in various matrices. The collected data, analyzed by using high-level quantum chemical calculations, confirmed that the tetraradical has a triplet ground state and a nearby excited quintet state. The unique high stability of the prepared triazinyl-nitronylnitroxide tetraradical is a new milestone in the field of creating high-spin systems.

Supramolecular have promising application prospects owing to their catalytic, self-healing, and stimulus-responsive functions. Pyridylethynylimidazole-based supramolecular synthons with fluorescent properties have been developed. 4-(2-Pyridylethynyl)-5-arylethynyl-1H-imidazole derivatives 1 with different substituents at the 4- and 5-positions of the imidazole skeleton were prepared using a step-by-step Sonogashira coupling reaction. The fluorescence maxima of phenyl- and methoxyphenyl-substituted derivatives 1a and 1c were independent of solvent polarity. On the other hand, ester- and cyano-substituted 1b and 1d showed bathochromically shifted fluorescence maxima in highly polar solvents. In crystals, the 4-(2-pyridylethynyl)-5-arylethynyl-1H-imidazole derivatives formed a supramolecular cyclic tetramer structure via two hydrogen bonds: one was between N─H in imidazole and N in pyridine, and the other was between C─H in imidazole and N in imidazole. Introducing the pyridine ring as a hydrogen bond acceptor, in addition to the imidazole ring, promoted the unique cyclic tetramer structure formation.

Organoboron complexes represented by BODIPY are one of the candidates for fluorescent skeletons exhibiting good fluorescence properties in the solution. However, because most BODIPY have high planar skeletons and small Stokes shifts, their fluorescence is quenched in the solid state. Therefore, numerous approaches were challenged to prepare the solid state fluorescent BODIPYs. On the other hand, an alternative approach to developing solid state fluorophores involves imidazole-boron complexes. Herein, imidazole-based boron complexes featuring the imidazo[1,2-c][1,3,2]diazaborole skeleton were synthesized. This skeleton comprised two fused five-membered rings and could introduce substituent at the 2-, 3-, 5-, and 6-positions. The boron complexes with aryl groups at the 3,5,6-positions exhibited fluorescence in both the solution and solid states. These compounds exhibited Stokes shifts exceeding 120 nm, effectively suppressing self-absorption. DFT calculations suggested that the large Stokes shift could be attributed to the planarization of π-conjugation upon excitation. In the solid state, the complexes displayed mechanofluorochromism, with the altered fluorescence color being recovered upon annealing at 150 °C. Compounds with two or three methoxy groups underwent a phase transition to a glass state, resulting in long-wavelength fluorescence. Furthermore, they demonstrated mechanochromism, thermochromism, and thermofluorochromism in the solid state, indicating their potential as scaffolds for multifunctional fluorophores.

5-Fluorobenzoyl-4-(4-methoxyphenyl)ethynyl-1-methylimidazole 1 exhibited a thermosalient effect without phase transition. The crystal of 1 was jumped by heating to about 80 °C using a hot plate. No phase transition peak was observed at this temperature range according to DSC measurement, unlike renowned thermosalient crystals. Variable-temperature X-ray crystal structure analyses revealed that anisotropical cell constant expansion resulting from the torsion angle change between the imidazole group and carbonyl moiety induced unit cell constant expansion and the thermosalient effect.

© 2018 Bentham Science Publishers. Background: Melanoma is the most aggressive type of skin cancer. Metastatic melanoma is extremely difficult to treat with current therapy methods such as surgery. On the other hand, it is a good opportunity to develop a radiopharmaceutical using a radionuclide such as Technetium (Tc) for diagnostic and Rhenium (Re) for therapeutic purposes. T3,4BCPP has been be used as a radioimaging agent for melanoma cancers experimentally. The aim of the present research was to design new imidazolylporphyrin derivatives with better selectivity and higher affinity than those of T3,4BCPP by molecular modeling. Methods: Eight types of Re-and Tc-labeled imidazolylporphyrins were docked to Fibroblast Growth Factor Receptor 1 (FGFR1, PDB ID: 5AM6) using AutoDock 4.2. FGFR1 was simulated by Molecular Dynamic (MD) simulation for 30 ns using NAMD 2.10 at 37 °C. The obtained conformations were then applied in a molecular docking simulation. Dovitinib (natural ligand of FGFR1), Re-and Tc-T3, 4BCPP were used as references. Results: The MD simulation resulted in an RMSD of 3.8 Å. From all the studied imidazolylporphyrin derivatives, Tc-cD3, 4BCPMIP and Re-cD3, 4BCPIP had the best docking parameter. Tc-cD3, 4BCPMIP had a free binding energy of 4.06 kcal/mol, while that of Re-cD3, 4BCPIP was 4.35 kcal/mol. Conclusion: It is concluded that cD3,4BCPMIP and cD3,4BCPIP are two potential candidate ligands for a melanoma radiopharmaceutical kit.

Novel V-shaped fluorophores with an imidazole skeleton composed of arylethynyl moieties were developed. Their HOMO-LUMO energy gaps were well controlled by the introduction of electron-withdrawing or -donating groups in the aryl moiety. Compounds with different substituents at the 4- and 5-positions were selectively synthesized exploiting the difference in reactivity between the iodo and bromo groups. All compounds synthesized displayed fluorescence not only in solution but also in the solid state. The compound with a donor-acceptor structure displayed a fluorescence maximum with a wavelength over 500 nm and a large Stokes shift of about 150 nm, due to its intramolecular charge transfer character. In the solid state, the synthesized compounds have planar structures, indicating an expansion of π-conjugation. Upon exposure of the compounds in the solid state to acid vapor, the fluorescence of the compounds with acceptor groups was quenched, and that of the others shifted to longer wavelengths.

Five known porphyrins, 5,10,15,20-tetrakis(p-tolyl)porphyrin (TTP), 5,10,15,20-tetrakis(p-bromophenyl)porphyrin (TBrPP), 5,10,15,20-tetrakis(p-aminophenyl)porphyrin (TAPP), 5,10,15-tris(tolyl)-20-mono(p-nitrophenyl)porphyrin (TrTMNP), 5,10,15-tris(tolyl)-20-mono(p-aminophenyl)porphyrin (TrTMAP), and three novel porphyrin derivatives, 5,15-di-[bis(3,4-ethylcarboxymethylenoxy)phenyl]-10,20-di(p-tolyl)porphyrin (DBECPDTP), 5,10-di-[bis(3,4-ethylcarboxymethylenoxy)phenyl]-15,20-di-(methylpyrazole-4-yl)porphyrin (cDBECPDPzP), 5,15-di-[bis(3,4-ethylcarboxymethylenoxy)phenyl]-10,20-di-(methylpyrazole-4-yl)porphyrin (DBECPDPzP), were used to study their interaction with protein targets (in silico study), and were synthesized. Their cytotoxic activities against cancer cell lines were tested using 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide (MTT) assay. The interaction of porphyrin derivatives with carbonic anhydrase IX (CAIX) and REV-ERBβ proteins were studied by molecular docking and molecular dynamic simulation. In silico study results reveal that DBECPDPzP and TrTMNP showed the highest binding interaction with REV- ERBβ and CAIX, respectively, and both complexes of DBECPDPzP-REV-ERBβ and TrTMNP-CAIX showed good and comparable stability during molecular dynamic simulation. The studied porphyrins have selective growth inhibition activities against tested cancer cells and are categorized as marginally active compounds based on their IC50.

Meso-tetrakis(1,2-dimethylpyrazolium-4-yl)porphyrin sulfonate (TDMPzP), a water-soluble porphyrin derivative, was synthesized and used as a colorimetric reagent for Cu2+ detection on a microfluidic paper-based analytical device (mu PAD) using distance-based quantification. TDMPzP showed a high selectivity for Cu2+ detection in aqueous solutions. When Cu2+ was added to the TDMPzP under acidic conditions, a color change from green to a pink was observed by the naked eye. Under optimized conditions, the application of this system to a distance-based mu PAD exhibited good analytical response. The presence of common metal ions (Al3+, Fe3+, Mg2+, Co2+, Mn2+, Zn2+, Pb2+, Cd2+, Sn2+, and Ni2+) did not interfere with Cu2+ detection within reasonable tolerance ratios. The lowest concentration of copper that could be measured was 1 mg L-1 (1 ppm) which meets the requirements for drinking water contamination regulations from the US Environmental Protection Agency (EPA) and World Health Organization (WHO) guidelines for drinking water. Real drinking water samples were analyzed to confirm the practical application of this system and the results showed good agreement with ICP-MS data. This distance-based mu PAD based on TDMPzP for Cu2+ detection is convenient and effective for real-time drinking water analysis.

Three dihydroacridine analogues, 2,7-dimethoxy-9,10-dihydro-9,9-diphenylacridine (1-C), 2,8-dimethoxy-10,10-diphenyl-5,10-dihydrophenazasiline (1-Si), and 2,8-dimethoxy-10,10-diphenyl-5,10-dihydrophenazagermine (1-Ge), and corresponding nitroxide radical derivatives, 2,7-dimethoxy-9,10-dihydro-9,9-diphenylacridine-10-oxyl (2-C), 2,8-dimethoxy-10,10-diphenyl-5,10-dihydrophenazasiline-5-oxyl (2-Si), and 2,8-dimethoxy-10,10-diphenyl-5,10-dihydrophenazagermine-5-oxyl (2-Ge) were synthesized in order to study the effect of the Si and Ge bridging atoms on the physicochemical properties of the diaryl nitroxide radical derivatives. These derivatives were stable in non-halogenated solvents and in the solid state. Their structures were crystallographically analyzed and UV-vis, fluorescence, EPR, and cyclic voltammetry measurements were performed to investigate the physicochemical properties of the dihydroacridine analogues and nitroxide radical derivatives.

Three dihydroacridine derivatives, 2,7-bis(4-methoxycarbonylphenyl)-9,9-diphenyl-9,10-dihydroacridine (1), 2,8-bis(4-methoxycarbonylphenyl)-10,10-diphenyl-5,10-dihydrophenazasiline (2), and 2,7,9,9-tetraphenyl-9,10-dihydroacridine (3), were prepared and their spectroscopic properties were investigated. These compounds exhibited relatively high quantum yields in a range of solvents. The emission spectra of 1 and 2 displayed large solvatochromic shifts, while the fluorescence solvatochromic behavior was not observed in 3. The intramolecular charge transfer (CT) process from the electron donating moiety at the NH site to the electron withdrawing ester moiety occurs in the excited states of 1 and 2. The increase in the dipole moment induced by the CT process was determined to cause the positive fluorescence solvatochromism. The differences between the excited and ground state dipole moments based on the Lippert-Mataga expression were estimated. The effect of the push-pull substitution in the dihydroacridine pi-conjugated system was also discussed using a computational method.

The synthesis and photophysical properties of cyano and ethynyl substituted carbazole-based porphyrins were investigated. The introduction of ethynyl groups induced red shifts, while that of cyano groups induced blue shifts of their absorption bands, which was supported by MO calculations. Ethylenedioxy-appended porphyrins were also prepared via a coupling reaction. The conjugated and electronic substituent effects on the photophysical properties of the carbazole-based porphyrins have been elucidated by using both experimental results and calculations. Among these porphyrins, the ethylenedioxy-appended selenaporphyrin displayed intensified and red-shifted absorption in the NIR region up to 1178 nm.