Recent advances in subphthalocyanines and related subporphyrinoids.

Half a century after the synthesis of the first subporphyrinoid, the study of tripyrrole and trisoindole porphyrin analogues constitutes a fervent and rapidly expanding research area. The outstanding structural, electronic and optical features of these cone-shaped aromatic macrocycles render them attractive candidates for a wide variety of applications, ranging from optoelectronics to biomedicine. To tune their properties and exploit their functionalities, the development of novel methodologies for the synthesis and post-functionalization of these contracted porphyrinoids, as well as a deep understanding of their supramolecular organization and their implementation into multicomponent systems of increasing complexity are of paramount importance. Herein, a review of the most recent advances in the fundamentals and applications of subporphyrinoids is presented, which comprehensively cover the last decade of discoveries. The final aim is to highlight the chemical versatility and intriguing physicochemical features of subporphyrinoids, while providing an updated overview of their most promising applications.

The unique features and promises of phthalocyanines as advanced photosensitisers for photodynamic therapy of cancer.

Phthalocyanines exhibit superior photoproperties that make them a surely attractive class of photosensitisers for photodynamic therapy of cancer. Several derivatives are at various phases of clinical trials, and efforts have been put continuously to improve their photodynamic efficacy. To this end, various strategies have been applied to develop advanced phthalocyanines with optimised photoproperties, dual therapeutic actions, tumour-targeting properties and/or specific activation at tumour sites. The advantageous properties and potential of phthalocyanines as advanced photosensitisers for photodynamic therapy of cancer are highlighted in this tutorial review.

Tuning the Acceptor Unit of Push-Pull Porphyrazines for Dye-Sensitized Solar Cells.

A family of four push-pull porphyrazines of A3B type, where each unit A contains two peripheral propyl chains and the unit B is endowed with a carboxylic acid, were prepared. The carboxylic acid was attached to the ß-position of the pyrrolic unit, either directly (Pz 10), or through cyanovinyl (Pz 11) and phenyl (Pz 7) groups. The fourth Pz (14) consisted in a pyrazinoporphyrazine wherein the dinitrogenated heterocycle provided intrinsic donor-acceptor character to the macrocycle and contained a carboxyphenyl substituent. The direct attachment of the carboxylic acid functions and their linkers to the porphyrazine core produces stronger perturbation on the electronic properties of the macrocycle, with respect to their connection through fused benzene or pyrazine rings in TT112 and 14, respectively. The HOMO and LUMO energies of the Pzs, which were estimated with DFT calculations, show little variation within the series, except upon introduction of the cyanovinyl spacer, which produces a decrease in both frontier orbital energetic levels. This effective interaction of cyanovinyl substitution with the macrocycle is also evidenced in UV/Vis spectroscopy, where a large splitting of the Q-band indicates strong desymmetrization of the Pz. The performance of the four Pzs as photosensitizers in DSSCs were also investigated.

Controlling Intramolecular Förster Resonance Energy Transfer and Singlet Fission in a Subporphyrazine-Pentacene Conjugate by Solvent Polarity.

Due its complementary absorptions in the range of 450 and 600 nm, an energy-donating hexaaryl-subporphyrazine has been linked to a pentacene dimer, which acts primarily as an energy acceptor and secondarily as a singlet fission enabler. In the corresponding conjugate, efficient intramolecular Förster resonance energy transfer (i-FRET) is the modus operandi to transfer energy from the subporphyrazine to the pentacene dimer. Upon energy transfer, the pentacene dimer undergoes intramolecular singlet fission (i-SF), that is, converting the singlet excited state, via an intermediate state, into a pair of correlated triplet excited states. Solvatochromic fluorescence of the subporphyrazine is a key feature of this system and features a red-shift as large as 20 nm in polar media. Solvent is thus used to modulate spectral overlap between the fluorescence of subporphyrazine and absorption of the pentacene dimer, which controls the Förster rate constant, on one hand, and the triplet quantum yield, on the other hand. The optimum spectral overlap is realized in xylene, leading to Förster rate constant of 3.52×1011  s-1 and a triplet quantum yield of 171 % ±10 %. In short, the solvent polarity dependence, which is a unique feature of subporphyrazines, is decisive in terms of adjusting spectral overlap, ensuring a sizable Förster rate constant, and maximizing triplet quantum yields. Uniquely, this optimization can be achieved without a need for synthetic modification of the subporphyrazine donor.

Highly Efficient Singlet Oxygen Generators Based on Ruthenium Phthalocyanines: Synthesis, Characterization and in vitro Evaluation for Photodynamic Therapy.

The synthesis of ruthenium(II) phthalocyanines (RuPcs) endowed with one carbohydrate unit-that is, glucose, galactose and mannose-and a dimethylsulfoxide (DMSO) ligand at the two axial coordination sites, respectively, is described. Two series of compounds, one unsubstituted at the periphery, and the other one bearing eight PEG chains at the isoindole meta-positions, have been prepared. The presence of the axial DMSO unit significantly increases the phthalocyanine singlet oxygen quantum yields, related to other comparable RuPcs. The compounds have been evaluated for PDT treatment in bladder cancer cells. In vitro studies have revealed high phototoxicity for RuPcs unsubstituted at their periphery. The phototoxicity of PEG-substituted RuPcs has been considerably improved by repeated light irradiation. The choice of the axial carbohydrate introduced little differences in the cellular uptake for both series of photosensitizers, but the phototoxic effects were considerably higher for compounds bearing mannose units.

Highly Efficient Singlet Oxygen Generators Based on Ruthenium Phthalocyanines: Synthesis, Characterization and in vitro Evaluation for Photodynamic Therapy.

Invited for the cover of this issue is the group of Torres at the University of Madrid. The image of the cover of this issue depicts cancer cells being destroyed by reactive singlet oxygen produced by ruthenium phthalocyanine glycoconjugates under red light. The work, developed at the Universities of Madrid, Aveiro, Lisbon and Coimbra, describes ruthenium phthalocyanines as powerful bladder cancer PDT agents. Read the full text of the article at 10.1002/chem.201903546.

Expanding the Subporphyrazine Chromophore by Conjugation of Phenylene and Vinylene Substituents: Rainbow SubPzs.

The efficiency of the vinylene moiety as a linker to intercommunicate the subporphyrazine (SubPz) core with other chromophores and redox active systems has been examined. In addition, different substitution patterns for hexaarylated SubPzs have been explored in order to control the absorption, fluorescence, and redox properties independently of one another. Besides X-ray crystallography, complete spectroscopic and electrochemical characterizations have been performed, and the conclusions have been supported by density functional theory calculations. The absorption and emission profiles, as well as the organization of the macrocycles in the crystalline state, are strongly determined by the substitution pattern. Within the hexaarylated family, para-substitution with electron-rich moieties (i.e., phenylene or ether) red-shifts both the SubPz absorption and emission bands. Progressive fading of these effects upon extending the oligophenylene branches from one to three units evidences the less efficient electronic delocalization over the phenyl ends as the oligophenylene branch is enlarged. Contrasting, meta-substitution produces little variation or blue shift of the SubPz Q-band, while bathochromic shifts are always observed for the emission bands. In hexavinylene-SubPzs, peripheral vinylene moieties adopt a coplanar configuration with the aromatic SubPz core, resulting in a π-extended chromophore that preserves the unique electronic tunability of SubPzs. This is reflected by the strong alteration of the SubPz electronic properties produced by phenyl and biphenyl moieties attached to the vinylene ends.

Panchromatic Photosensitizers Based on Push-Pull, Unsymmetrically Substituted Porphyrazines.

A series of five push-pull porphyrazines of A3 B type, in which unit B is an isoindole 4-carboxylic acid, has been prepared. The units A have been endowed with thioether, amine, ether and alkyl functions, either directly attached to the ß-position of the pyrrolic units, or connected to the porphyrazine core through p-substituted phenyl groups. Attaching the electron-donor functions to the porphyrazine periphery produces strong perturbations in the electronic and redox properties of the dyes. Their HOMO and LUMO energies, estimated from the optical and redox data, as well as with DFT calculations, raise upon functionalization with amines, while the corresponding frontier orbital energetic levels lower upon functionalization with thioethers, p-methoxyphenyl or p-tert-butylphenyl groups. The effective interaction of peripheral substitution with the macrocycle produces chromophores with panchromatic absorption between 300 and 750-850 nm.

Phthalocyanine-Perylenediimide Cart Wheels.

The electronic features of Zn(II) and Ru(II) phthalocyanines (Pcs) have been modulated by direct peripheral attachment of up to eight ferrocenes. The presence of peripheral ferrocenes noticeably impacts the electronic properties of the corresponding ZnPc and RuPc complexes 7, 12 and 9, 15, respectively-a notion that is supported by optical spectroscopy with bathochromic shifts of up to 8-10 nm per ferrocene unit. Cyclic voltammetry and optical spectroscopy reveal long-distance (10-11 bonds) electronic interaction between ferrocene units. The ZnPc and RuPc complexes have been integrated into a series of orthogonal, supramolecular bis(phthalocyanine)-perylenediimide electron donor-acceptor conjugates, 2a,b and 3a,b. In these cart-wheel-shaped arrays, coordination of ditopic perylenediimide 16, containing two pyridyl substituents at its imido positions, enabled selective interactions with the metal centers of phthalocyanines 7, 12, 9, and 15. The presence of ferrocenes in, for example, Zn complexes 2a and 3a triggers a fast energy transfer from the excited-state PDI to ZnPc. In the RuPc-PDI conjugates, substitution with ferrocenes produces a slight acceleration of the charge separation upon photoexcitation of the PDI chromophore. However, charge recombination is accelerated by 2 orders of magnitude in ferrocene-containing conjugates when compared to that in the analogous tert-butyl-substituted array 1b.

Tuning the Electron Acceptor in Phthalocyanine-Based Electron Donor-Acceptor Conjugates.

Zinc phthalocyanines (ZnPc) have been attached to the peri-position of a perylenemonoimide (PMI) and a perylenemonoanhydride (PMA), affording electron donor-acceptor conjugates 1 and 2, respectively. In addition, a perylene-monoimide-monoanhydride (PMIMA) has been connected to a ZnPc through its imido position to yield the ZnPc-PMIMA conjugate 10. The three conjugates have been studied for photoinduced electron transfer. For ZnPc-PMIMA 10, electron transfer occurs upon both ZnPc and PMIMA excitation, giving rise to a long-lived (340 ps) charge-separated state. For ZnPc-PMI 1 and ZnPc-PMA 2, stabilization of the radical ion pair states by using polar media is necessary. In THF, photoexcitation of either ZnPc or PMI/PMA produces charge-separated states with lifetimes of 375 and 163 ps, respectively.

Tuning electron donor-acceptor hybrids by alkali metal complexation.

A zinc phthalocyanine endowed with four [18]-crown-6 moieties, ZnPcTeCr, has been prepared and self-assembled with either pyridyl-functionalized perylenebisimides (PDI-Py) or fullerenes (C60-Py) to afford a set of novel electron donor-acceptor hybrids. In the case of ZnPcTeCr, aggregation has been circumvented by the addition of potassium or rubidium ions to lead to the formation of monomers and cofacial dimers, respectively. From fluorescence titration experiments, which gave rise to mutual interactions between the electron donors and the acceptors in the excited state, the association constants of the respective ZnPcTeCr monomers and/or dimers with the corresponding electron acceptors were derived. Complementary transient-absorption experiments not only corroborated photoinduced electron transfer from ZnPcTeCr to either PDI-Py or C60-Py within the electron donor-acceptor hybrids, but also the unexpected photoinduced electron transfer within ZnPcTeCr dimers. In the electron donor-acceptor hybrids, the charge-separated-state lifetimes were elucidated to be close to 337 ps and 3.4 ns for the two PDI-Pys, whereas the longest lifetime for the photoactive system that contains C60-Py was calculated to be approximately 5.1 ns.

Ruthenoarenes versus phenol derivatives as axial linkers for subporphyrazine dimers and trimers.

The subporphyrazine (SubPz) dimer diboron(III) [µ-1',4'-benzenediolato][bis-(1,2,6,7,11,12-hexapropylsubporphyrazinato)] (2) and trimer triboron(III)[µ-1',3',5'-benzenetriolato][tris-(1,2,6,7,11,12-hexapropylsubporphyrazinato)] (4), consisting of SubPz units assembled through their axial positions by hydroquinone- and phloroglucinol-linkers, respectively, have been prepared. Selective ruthenium-π-coordination to the linking aromatic rings afforded SubPz arrays 8 and 9, respectively. These latter systems displayed different degrees of electronic communication between the macrocycles relative to 2 and 4 as inferred from analyses of the ground- and excited-state features. For instance, as revealed by time-resolved pump probe transient absorption spectroscopy, the excited singlet states of dimer 2 and trimer 4 undergo rather rapid deactivation. In contrast, the presence of a ruthenoarene linker, as in 8 and 9, serves to increase the SubPz singlet excited state lifetimes; these now reach values similar to those seen in the case of monomeric SubPz compounds that either do or do not contain ruthenoarene subunits (i.e., 7 and 6, respectively). These findings are ascribed to the redox active nature of the hydroquinone and phloroglucinol linkers in 2 and 4 and a change in the electronics that results from organometallic functionalization.

A Green-to-Near-Infrared Photoswitch Based on a Blended Subporphyrazine-Dithienylethene System.

A subporphyrazine (SubPz)-dithienylethene (DTE) photochromic device with 1o and 1c states, was developed and characterized. In this device, the DTE unit can reversibly switch the SubPz absorbance from green to near-infrared [λmax (o/c) = 527 nm/740 nm], as well as the SubPz fluorescence and singlet oxygen quantum yields. The core of this design involves using a highly tunable SubPz chromophore that shares its quasi-isolated ethene moiety with a DTE photoswitch.

Tuning Fluorescence and Singlet Oxygen Quantum Yields of Subporphyrazines by Axial Functionalization.

The axial functionalization of Subporphyrazines (SubPzs) with unreported alkoxy groups, carboxy and carboperoxy rests, as well as sulfanyl, aryl and amino groups, forming B-O, B-S, B-C, and B-N bonds, respectively, has been investigated. The studied oxygen nucleophiles include aromatic and sterically demanding aliphatic alcohols, along with carboxylic acids and peracids. In general, direct substitution of the chloro-SubPz by oxygen nucleophiles of diverse nature proceeds smoothly, with yields of the isolated alkoxy and carboxy-substituted SubPzs ranging from 49 to 100 %. Conversely, direct substitution with sulphur, carbon and nitrogen nucleophiles do not afford the corresponding substituted SubPzs. In these cases, a stepwise procedure involving an axial triflate-SubPz intermediate was employed, affording only the phenyl-SubPz in 8 % yield. The major compound under these conditions was the unreported SubPz µ-oxo dimer, presumably arising from substitution of the triflate-SubPz by the in situ generated hydroxy-SubPz. This result indicates a quite low reactivity of the TfO-SubPz intermediate with carbon, sulphur and nitrogen nucleophiles. All SubPzs prepared in this work exhibited fluorescence at 510-515 nm with quantum yields ranging from 0.1 to 0.24. Additionally, all SubPzs generated singlet oxygen, with ΦΔ values ranging from 0.15 to 0.57, which show no apparent correlation with the axial substituents.

Peripheral arylation of subporphyrazines.

Peripherally hexaarylated subporphyrazines (SubPzs) have been prepared through a Pd-catalyzed, CuTC-mediated coupling of a hexaethylsulfanylated subporphyrazine with arylboronic acids. The introduced aryl substituents strongly influence the electronic properties of the subporphyrazine through effective conjugative interaction. Aryl rings endowed with π-electron-donating groups at the para positions produce a remarkable perturbation of the electron density of the SubPz macrocycle. This is reflected through significant redshifts of the SubPz CT and Q-bands, together with increase of the molar absorptivity of the former, with respect to those exhibited by the hexaphenyl-SubPz 2 a. Moreover, the trend in the first SubPz reduction potentials correlates with the Hammett constants (σp ) corresponding to the para substituents of the aryl. The domed, extended SubPz π-system self-assembles in the solid state to form a dimeric capsule that houses a solvent molecule.

Assembling a phthalocyanine and perylenediimide donor-acceptor hybrid through a platinum(II) diacetylide linker.

In a novel electron-donor-acceptor conjugate, phthalocyanine (Pc) and perylenediimide (PDI) are connected through a trans-platinum(II) diacetylide linker to yield Pc-Pt-PDI 1. In the ground state, the presence of Pt(II) disrupts the electronic communication between the two electroactive components, as revealed by UV/Vis spectroscopy and electrochemical studies. The photophysical behavior of 1 is compared with that of the corresponding Pc-PDI electron-donor-acceptor conjugate 2 in terms of charge separation and charge recombination. The insertion of Pt(II) between Pc and PDI impacts the results in a longer-lived Pc(.) (+) /PDI(.) (-) radical ion-pair state. In addition, the intermediately formed Pc triplet excited state is formed with higher quantum yields in 1 than in 2.

Cyclopentadienylruthenium π complexes of subphthalocyanines: a "drop-pin" approach to modifying the electronic features of aromatic macrocycles.

Facing facts: Coordination of Cp*Ru (Cp*=C(5)Me(5)) to the concave and convex π surfaces of subphthalocyanines constitutes a new approach to the functionalization of subazaporphyrins. While the convex face shows higher reactivity, coordination to the concave side produces a stronger diatropic influence on the Cp* ligand and a greater perturbation of the macrocyclic π-electronic features.

Assembling phthalocyanine dimers through a platinum(II) acetylide linker.

Phthalocyanine (Pc) dimers connected through trans-platinum(II) diacetylide linkers have been prepared by reaction of the corresponding ethynylphthalocyanines with trans-bis(triethylphosphine)platinum(II) chloride. Special emphasis was placed on the analysis of the ground- and excited-state features of these compounds in relation to butadiyne-bridged Pc dimers and the corresponding monomers. Both Zn(II)-containing Pc dimers exhibit long-lived triplet excited states. The insertion of σ-bonded trans-platinum(II) diacetylide spacers decoupled the two Pc groups and led to an appreciable acceleration (by a factor of up to 10) of the radiative and nonradiative decay rate of the singlet and triplet excited states.

Synthesis, characterization, and photoinduced energy and electron transfer in a supramolecular tetrakis (ruthenium(II) phthalocyanine) perylenediimide pentad.

Metal coordination was probed as a versatile approach for designing a novel electron donor/acceptor hybrid [PDIpy(4){Ru(CO)Pc}(4)] (1), in which four pyridines placed at the bay region of a perylenediimides (PDIpy(4)) coordinate with four ruthenium phthalocyanine units [Ru(CO)Pc]. This structural motif was expected to promote strong electronic coupling between the electron donors and the electron acceptor, a hypothesis that was confirmed in a full-fledged physicochemical investigation focusing on the ground and excited state reactivities. As far as the ground state is concerned, absorption and electrochemical assays indeed reveal a notable redistribution of electron density, that is, from the electron-donating [Ru(CO)Pc] to the electron-accepting PDIpy(4). The most important thing to note in this context is that both the [Ru(CO)Pc] oxidation and the PDIpy(4) reduction are rendered more difficult in 1 than in the individual building blocks. Likewise, in the excited state, strong electronic communication is the inception for a rapid charge-transfer process in photoexcited 1. Regardless of exciting [Ru(CO)Pc] or PDIpy(4), spectral characteristics of the [RuPc] radical cation (broad absorptive features from 425 to 600 nm with a maximum at 575 nm, as well as a band centered at 725 nm) and of the PDI radical anion (780 nm maximum) emerge. The correspondingly formed radical ion pair state lasts for up to several hundred picoseconds in toluene, for example. On the other hand, employing more polar solvents, such as dichloromethane, destabilizes the radical ion pair state.