A Doubly meso-α Linked N-Confused Porphyrin Tape Silver(III) Complex Comprising an Antiaromatic Pyrrolo[2,3-f]indole Segment.

The free base form of doubly meso-α linked N-confused porphyrin (NCP) tape 3 was successfully synthesized via Ir(I) mediated intramolecular coupling. The following silver complexation afforded the Ag(III) complex of doubly meso-α linked NCP tape 4. While 3 exhibited 38π aromatic characters, 4 exhibited not only 18π aromatic NCP-type characteristics but also a decent antiaromatic contribution of 12π pyrrolo[2,3-f]indole segment, as probed by NMR spectra, absorption spectra, and DFT calculations.

2,5-Thienylene-Strapped [26]Hexaphyrin as Multifunctional Chemosensor for Hg2+, Cu2+, and F- Ions.

The sensing behavior of 2,5-thienylene-bridged tetrakis(2,6-dichlorophenyl)-[26]hexaphyrin (2) towards various metal ions and anions were investigated by UV-vis and fluorescence spectroscopies. Using this strapped hexaphyrin (2), the molecular sensor displayed highly selective and sensitive colorimetric responses to Cu2+ and Hg2+ in MeOH/THF. The spectral changes are distinctive enough in the visible region of the spectrum to enable naked-eye detection. The detection limits of Cu2+ and Hg2+ using this chemo-sensor in a mixed MeOH/THF solution were 1.978 and 1.283 µM, respectively, and 1.052 µM for F- in dichloromethane. Chemosensor 2,5-thienylene strapped [26]hexaphyrin (2) shows absorption responses both a 1 : 1 molecular ratio for 2 interacting with Cu2+ and Hg2+ and a 1 : 2 ratio between 2 and F- ions.

Gated Photochromism of Dithienylethene-Embedded Expanded Calixphyrins.

Dithienylethene (DTE)-embedded expanded porphyrins were synthesized and confirmed to be photochemically inactive due to the lowest excited state of the expanded porphyrins. On the other hand, DTE-embedded expanded calixphyrins exhibited reversible photochromism upon UV-irradiation to form colored closed forms, which reverted to colorless open forms upon red-light irradiation. The closed forms were oxidized with DDQ or the air to lock the recorded information by converting to photochemically inactive expanded porphyrins. This was unlocked by reduction with NaBH4 to restore expanded calixphyrins with photochromism activity. These gated photochromic behaviors were demonstrated in PMMA (polymethyl methacrylate) film.

Rearrangements of Internally-bridged Octaphyrin(1.1.1.1.1.1.1.1)s to Porphyrin Dimers.

Internally-bridged octaphyrin(1.1.1.1.1.1.1.1) underwent a rearrangement to meso-meso linked porphyrin dimer as a new metamorphosis. Extensive examination suggests that hydride-addition is a key step for the rearrangements to afford thermodynamically more stable porphyrin framework. Further, ß-tetrabromo[36]octaphyrin was transformed to meso-meso, ß-ß, ß-ß triply linked porphyrin dimer via a similar mechanism combined with Pd-mediated reductive homocoupling.

Di-2,7-pyrenidecaphyrin(1.1.0.0.0.1.1.0.0.0) and Its Bis-Organopalladium Complexes: Synthesis and Chiroptical Properties.

A non-aromatic expanded carbaporphyrinoid, incorporating two built-in 2,7-pyrenylene moieties was synthesized. The intrinsically labile structure was demonstrated by proton-triggered conformational changes between the figure-of-eight and quasi-Möbius conformers. Upon treatment with Pd(OAc)2 , the reaction produces two bis-PdII complexes with distinct coordination modes. Metal coordination serves to fix the macrocyclic frameworks with the net result that both bis-PdII complexes could be resolved by high performance liquid chromatography (HPLC) on a chiral stationary phase. The isolated enantiomers showed persistent chiroptical properties as evidenced by the intense response in the circular dichroism (CD) spectra and the record high absorption dissymmetry factors (gabs of up to 0.038) seen in the near-infrared spectral region. Moreover, the mutual interconversion of these two PdII complexes was found to be stereospecific and to favor the more stable isomers under weakly acidic conditions.

Synthesis of meso-Free Decaphyrin(1.1.1.1.1.1.1.1.1.1) by a Hydrodebromination Protocol; Aromaticity and Solvent-Polarity Dependent Conformational Change.

A meso-free ß-bromodecaphyrin has been constructed by [2+3+2+3] type acid-catalyzed cross-condensation and subsequent oxidation. Hydrodebromination of this tetrabromodecaphyrin with NaBH4 in the presence of TMEDA and palladium catalyst afforded ß-unsubstituted doubly meso-free [46]decaphyrin(1.1.1.1.1.1.1.1.1.1) as the first example of ß-unsubstituted meso-free regular expanded porphyrins with the number of pyrrole units larger than eight. It exhibits distinct aromaticity originating from its 46π-conjugated electronic circuit and flexible conformational change between non-twisted and doubly twisted forms depending on the solvent-polarity. Their distinct conformations have been analyzed by combined experimental and theoretical investigations.

Meso-Carbon Atom Nucleophilic Attack Susceptibility in the Sterically Strained Antiaromatic Bis-BODIPY Macrocycle and Extended Electron-Deficient BODIPY Precursor.

A sterically strained 32π-electron antiaromatic bis-BODIPY macrocycle in which two BODIPY fragments are linked by p-divinylbenzene groups was prepared and characterized. Unlike regular BODIPYs, the fluorescence in this macrocycle is quenched. The broad signals in the NMR spectra of the macrocycle were explained by the vibronic freedom of the p-divinylbenzene fragments. The possible diradicaloid nature of the macrocycle was excluded on the basis of variable-temperature EPR spectra in solution and in solid state, which is indicative of its closed-shell quinoidal structure. The meso-C-H bond in the macrocycle and its precursor BODIPY dialdehyde 3 forms a weak hydrogen bond with THF and is susceptible for the nucleophilic attack by organic amines and cyanide anion. The reaction products of such a nucleophilic attack have meso-sp3 carbon atoms and were characterized by NMR, mass spectrometry and, in one case, X-ray crystallography. Unlike the initial bis-BODIPY macrocycle, the adducts have strong fluorescence in the 400 nm region. The electronic structure and spectroscopic properties of new chromophores were probed by density functional theory (DFT) and time-dependent DFT (TDDFT) calculations and correlate well with the experimental data.

A Fully Conjugated Porphyrin-[36]Octaphyrin-Porphyrin Hybrid Tape Exhibiting Möbius Aromaticity.

Directly meso-meso linked porphyrin-tetrabromo[36]octaphyrin-porphyrin hybrid trimer 10 was successfully synthesized via acid-catalyzed condensation reaction and subsequent oxidation. ZnII -metalation of 10 induced transannular meso-meso bond formation to give Möbius aromatic bis-ZnII octaphyrin 11, which was oxidized by DDQ/Sc(OTf)3 to provide fully conjugated porphyrin-[36]octaphyrin-porphyrin hybrid tape 12 as the first example of porphyrin tape exhibiting Möbius aromaticity. Hybrid tape 12 displays significantly red-shifted absorption and small electrochemical HOMO-LUMO gap, indicating the effective conjugation through the whole chromophores.

Vinylene-Bridged Cyclic Dipyrrin and BODIPY Trimers.

Vinylene-bridged cyclic boron-difluoride complex of dipyrrin (BODIPY) trimers were successfully prepared from expanded dimethyl-vinylene bridged hexaphyrin(2.1.2.1.2.1) Me-Hex that has the structure of alternate dipyrrins and vinylene bridges. The hexaphyrin(2.1.2.1.2.1) Me-Hex can coordinate with boron ions to afford five kinds of cyclic BODIPYs given by step-by-step boron complexations. Crystal structures of all cyclic BODIPYs except for 3BF2-Me-Hex(b) formed non-planar structures. The theoretical calculation predicted that mono-/bis-boron cyclic BODIPYs show the intramolecular charge transfer (ICT) characteristics, whereas tri-boron cyclic BODIPYs have no ICT characteristics. Reflecting these electronic properties, tri-boron cyclic BODIPYs exhibit weak fluorescence in the red region, but mono-/bis-boron cyclic BODIPYs exhibit no emission. Vinylene bridged cyclic dipyrrin trimer Me-Hex is the novel porphyrinoid ligand allowed to control the boron coordination under different reaction conditions to form various boron complexes.

Dicarba[26]hexaporphyrinoids(1.1.1.1.1.1) with an Embedded Cyclopentene Moiety-Conformational Switching.

Incorporation of cyclopentene fragments into a skeleton of parental [26]hexaphyrin(1.1.1.1.1.1) afforded extended carbaporphyrinoids: 31,34-dicarbahexa[26]chlorin and its derivatives: the first externally substituted by ethoxy and 2,4,6-trimethylbenzylidene groups and the second one formed by selective oxidation of one cyclopentene ring. Macrocycles adopt dumbbell-shaped conformations with two meso hydrogen atoms located inside the macrocyclic cavity. Protonation of 31,34-dicarba[26]hexachlorins provided dications existing in dumbbell-shaped and rectangular conformations.

Oxidation-Induced Detachment of Ruthenoarene Units and Oxygen Insertion in Bis-Pd(II) Hexaphyrin π-Ruthenium Complexes.

Two types of new bis-Pd(II) hexaphyrin π-ruthenium complexes are reported. A double-decker bis-Pd(II) hexaphyrin π-ruthenium complex 4 was obtained by oxidation-induced detachment of a ruthenoarene unit from the triple-decker complex 3 and oxygen-inserted triple-decker bis-Pd(II) hexaphyrin π-ruthenium complex 6 was obtained upon treatment of bis-Pd(II) [26]hexaphyrin 5 with [RuCl2(p-cymene)]2 under aerobic conditions. Although π-metal complexation of porphyrinoids often results in decreased global aromaticity due to the enhancement of local 6π aromatic segments, distinct aromatic characters were indicated for 4 and 6 by 1H-NMR spectral and theoretical calculations. These results are accounted for in terms of possible resonance contributors of hexaphyrin di- and tetraanion ligands. Thus, π-metal coordination has been shown to be effective for modulation of the overall aromaticity.

Metallotexaphyrins as MRI-Active Catalytic Antioxidants for Neurodegenerative Disease: A Study on Alzheimer's Disease.

The complex etiology of neurodegeneration continues to stifle efforts to develop effective therapeutics. New agents elucidating key pathways causing neurodegeneration might serve to increase our understanding and potentially lead to improved treatments. Here, we demonstrate that a water-soluble manganese(II) texaphyrin (MMn) is a suitable magnetic resonance imaging (MRI) contrast agent for detecting larger amyloid beta constructs. The imaging potential of MMn was inferred on the basis of in vitro studies and in vivo detection in Alzheimer's disease C. elegans models via MRI and ICP-MS. In vitro antioxidant- and cellular-based assays provide support for the notion that this porphyrin analog shows promise as a therapeutic agent able to mitigate the oxidative and nitrative toxic effects considered causal in neurodegeneration. The present report marks the first elaboration of an MRI-active metalloantioxidant that confers diagnostic and therapeutic benefit in Alzheimer's disease models without conjugation of a radioisotope, targeting moiety, or therapeutic payload.

Figure-eight Octaphyrin Bis-Ge(IV) Complexes: Synthesis, Structures, Aromaticity, and Chiroptical Properties.

Highly twisted structures of expanded porphyrin provide a prominent basis to unravel the relationship between aromaticity and chirality. Here we report the synthesis of bis-Ge(IV) complexes of [38]octaphyrin that display rigid figure-eight structures. Two bis-Ge(IV) [38]octaphyrin isomers with respect to the stereochemistry of the axial hydroxy groups on the germanium ions were obtained and found to be aromatic. Upon oxidation with MnO2 , these [38]octaphyrin complexes were converted to a single syn-type isomer of [36]octaphyrin with retained figure-eight conformation. The enantiomers have been successfully separated by HPLC equipped with a chiral stationary phase. While aromatic [38]octaphyrin Ge(IV) complexes showed quite large molar circular dichroism of up to Δϵ=1500 M-1 cm-1 with a dissymmetry factor gabs of 0.035, weakly antiaromatic [36]octaphyrin Ge(IV) complexes underscored moderate values; Δϵ=540 M-1 cm-1 with gabs of 0.023. Thus, the figure-eight octaphyrin scaffold has been proved to be an attractive platform for novel chiroptical materials with tunable aromaticity.

Synthesis and Characterization of a Binuclear Copper(II)-dipyriamethyrin Complex: [Cu2(dipyriamethyrin)(µ2-1,1-acetato)2].

The reaction between dipyriamethyrin and copper(II) acetate [Cu(OAc)2] afforded what is, to our knowledge, the first transition metal-dipyriamethyrin complex. Molecular and electronic characterization of this binuclear Cu(II) complex via EPR, UV-vis, and single crystal X-ray diffraction analysis revealed marked differences between the present constructs and previously reported binuclear copper(II) hexaphyrin species. UV-vis titration analyses provided evidence for a homotropic positive allosteric effect, wherein the binuclear species is formed without significant intermediacy of a monomeric complex.

Aromatic and Antiaromatic Cyclophane-type Hexaphyrin Dimers.

A peripherally strapped [28]hexaphyrin takes a rectangular conformation and exhibits antiaromatic character. A cyclophane-type dimer consisting of such [28]hexaphyrins was synthesized from hexakis(pentafluorophenyl) [26]hexaphyrin via SN Ar reaction with allyl alcohol, one-pot intra- and intermolecular olefin metathesis under improved Hoveyda-Grubbs catalysis, and final reduction with NaBH4 . The cyclophane-type structures of [26]- and [28]hexaphyrin dimers have been revealed by X-ray analysis. Studies on the structural, optical, and electronic properties have led to a conclusion that there is no favorable electronic interaction between the two [28]hexaphyrin segments and thus no indication of 3D aromaticity.

Relevance of the DFT method to study expanded porphyrins with different topologies.

Meso-aryl expanded porphyrins present a structural versatility that allows them to achieve different topologies with distinct aromaticities. Several studies appeared in the literature studying these topological switches from an experimental and theoretical point of view. Most of these publications include density functional theory calculations, being the B3LYP the most used methodology. In this work, we show that the selection of the functional has a critical role on the geometric, energetic, and magnetic results of these expanded porphyrins, and that the use of an inadequate methodology can even generate spurious stationary points on the potential energy surface. To illustrate these aspects, in this article we have studied different molecular distortions of two expanded porphyrins, [32]-heptaphyrin and [26]-hexaphyrin using 11 DFT functionals and performing single point energy calculations at the local pair natural orbital coupled cluster DLPNO-CCSD(T) method, which have been carried out for benchmarking purposes. For some selected functionals, the dispersion effects have also been evaluated using the D3-Grimme's dispersion correction with Becke-Johnson damping. Our results let us to conclude that the CAM-B3LYP, M05-2X, and M06-2X functionals are the methodologies that provide a more consistent description of these topological switches, while other methods, such as B3LYP, BPE, and BP86, show a biased description. © 2017 Wiley Periodicals, Inc.

Internally 2,5-Thienylene-Bridged [46]Decaphyrin: (Annuleno)annulene Network Consisting of Möbius Aromatic Thia[28]hexaphyrins and Strong Hückel Aromaticity of its Protonated Form.

Internally 1,3-phenylene- and 2,5-thienylene-bridged [46]decaphyrins 2 and 3 have been synthesized. While 2 shows modest aromatic character derived from the global 46π-conjugated circuit, 3 displays larger aromatic character owing to the contribution of an (annuleno)annulene-type network consisting of two twisted Möbius aromatic thia[28]hexaphyrin segments in addition to the global 46π-network. Upon protonation, these [46]decaphyrins underwent large structural changes to acquire strong aromaticity. Protonated 3 has been revealed to take on a planar structure composed of fused two triangular thia[28]hexaphyrin segments.

Hexaphyrin as a Potential Theranostic Dye for Photothermal Therapy and 19 F Magnetic Resonance Imaging.

Two features of meso-Aryl-substituted expanded porphyrins suggest suitability as theranostic agents. They have excellent absorption in near infrared (NIR) region, and they offer the possibility of introduction of multiple fluorine atoms at structurally equivalent positions. Here, hexaphyrin (hexa) was synthesized from 2,6-bis(trifluoromethyl)-4-formyl benzoate and pyrrole and evaluated as a novel expanded porphyrin with the above features. Under NIR illumination hexa showed intense photothermal and weak photodynamic effects, which were most likely due to its low excited states, close to singlet oxygen. The sustained photothermal effect caused ablation of cancer cells more effectively than the photodynamic effect of indocyanine green (a clinical dye). In addition, hexa showed potential for use in the visualization of tumors by 19 F magnetic resonance imaging (MRI), because of the multiple fluorine atoms. Our results strongly support the utility of expanded porphyrins as theranostic agents in both photothermal therapy and 19 F MRI.

A Doubly Zwitterionic Antiaromatic [28]Hexaphyrin Formed upon Deprotonation of 5,20-Di(N-methyl-4-pyridinium)-Substituted [28]Hexaphyrin.

A rectangular 5,20-di(4-pyridyl) [26]hexaphyrin was reduced with NaBH4 to give the corresponding twisted Möbius aromatic [28]hexaphyrin. Subsequent double N-methylation gave a dicationic 5,20-di(N-methyl-4-pyridinium) [28]hexaphyrin, which was converted to a doubly zwitterionic and Hückel antiaromatic [28]hexaphyrin upon deprotonation with sodium methoxide.

[62]Tetradecaphyrin and Its Mono- and Bis-Zn(II) Complexes.

A coiled structure of meso-pentafluorophenyl-substituted [62]tetradecaphyrin 1 was revealed by X-ray structural analysis. Synthetic protocols were devised to form mono- and bis-Zn(II) complexes, 1 Zn and 1 Zn2 , selectively. The former displayed a trigonal-bipyramidal pentacoordinated Zn(II) ion as a rare case and a cyclic voltammogram exhibiting eleven reversible redox waves. The latter showed a Ci-symmetric structure with modest Hückel aromaticity owing to a 62 π-electronic circuit as the largest aromatic molecule to date.