Revisiting the Ullman's Radical Chemistry for Phthalocyanine Derivatives.

Phthalocyanine derivatives do not cease to gain attention due to their numerous properties and applications (e.g., sensor, PDT). This makes them a unique scaffold for the design of new material. In this context, we were interested to develop the synthesis of an imino nitroxide-substituted phthalocyanine by Ullman's procedure; a challenge due to the intrinsic low solubility of most phthalocyanine derivative in much solvents. To overcome this solubility problem, we designed a phthalocyanine with bulky neopentyl substituents in peripheral positions as counterpart to the imino nitroxide moieties. The imino nitroxide-substituted phthalocyanine was obtained by condensation of a monoformyl-substituted phthalocyanine with 2,3-bis(hydroxylamino)-2,3-dimethylbutane in refluxing THF-MeOH (2:1) mixture in the presence of p-toluenesulfonic acid monohydrate, follow by oxidation with PbO2 . Characterization was performed by electrochemistry, UV/Vis and EPR spectroscopy in solution as well as SQUID in solid state.

Effect of the Substitution Pattern (Peripheral vs Non-Peripheral) on the Spectroscopic, Electrochemical, and Magnetic Properties of Octahexylsulfanyl Copper Phthalocyanines.

In order to investigate the substitution position effect on the spectroscopic, electrochemical, and magnetic properties of copper phthalocyanines, a detailed structure-property analysis has been performed by examining two copper phthalocyanines that are octasubstituted by hexylsulfanyl chains respectively in the peripheral (Cu-P) and non-peripheral (Cu-NP) positions. Cu-NP showed a marked near-IR maximum absorption compared to Cu-P and, accordingly, a smaller HOMO-LUMO energy gap, calculated via the electrochemical results and simulations in the gas phase, as well as for Cu-NP from its crystallographic data. An electron-spin resonance (ESR) technique is used to extract the g values from the powder spectra that are taken at room temperature. The g values were determined to be g∥ = 2.160 and g⊥ = 2.045 for Cu-P and g∥ = 2.150 and g⊥ = 2.050 for Cu-NP. These values indicate that the paramagnetic copper center in both phthalocyanines has axial symmetry with a planar anisotropy ( g∥ > g⊥). The ESR spectra in solution could be obtained only for Cu-P. Curie law is used to fit the experimental data of the magnetic susceptibility versus temperature graphs, and the Curie constant ( C) and diamagnetic/temperature-independent paramagnetic (α) contributions are deduced as 0.37598 (0.39576) cm3·K/mol and -23 × 10-5 (25 × 10-5) cm3/mol respectively for Cu-P and Cu-NP. The room temperature magnetic moment value (1.70 µB) is close to the spin-only value (1.73 µB) for the peripheral complex, showing that there is no orbital contribution to µeff. In contrast, at room temperature, the value of the magnetic moment (1.77 µB) is above the spin-only value, showing an orbital contribution to the magnetic moment. Cu-NP's room temperature magnetic moment value is larger than the value for Cu-P, demonstrating that the orbital contribution to the magnetic moment depends upon the substituent position. The magnitudes of the effective magnetic moment values also support that both Cu-P and Cu-NP complexes have square-planar coordination. This result is consistent with the determined g values. The spin densities were determined experimentally, and the results suggest that the positions of the substituents affect these values (0.469 for Cu-P and 0.490 for Cu-NP).

Structure-Photoproperties Relationship Investigation of the Singlet Oxygen Formation in Porphyrin-Fullerene Dyads.

A systematic structure-photoproperties relationship study of the interactions of porphyrin-fullerene dyads with molecular oxygen was conducted on a set of three porphyrin-fullerene dyads, as this approach of related applications - oxygen sensitivity and photo-induced singlet oxygen generation - of such dyads remained to be endeavoured. To promote energy transfers between the porphyrin and fullerene units and limit undesired charge separation, a particular attention was devoted to the choice of the solvents for the photoproperties determination. Toluene, in which in addition the compounds investigated are not aggregated, was selected accordingly. The molecular orbital levels and energy gaps of the dyads were determined by electrochemistry and theoretical calculations. Their ground state absorption, steady-state fluorescence-based oxygen sensitivity and photo-induced singlet oxygen generation were determined. The dyads were designed to benefit from a facilitated synthetic porphyrin-fullerene coupling thanks to an easy access to formyl-functionalized porphyrins. The effect of two structural parameters was investigated: the presence of electron-donating hexyloxy chains at the para position of the meso-phenyl, and the presence of a phenylacetylene spacer. This latest factor appeared to have the most predominant effect on all these properties.

Lifetime-Based Oxygen Sensing Properties of palladium(II) and platinum(II) meso-tetrakis(4-phenylethynyl)phenylporphyrin.

High oxygen permeable [poly(TMSP)] nanofibers incorporating porphyrin macrocycle as luminescence indicators were prepared by electrospinning technique. The porphyrins involves were modified by i) introducing phenylacetylide substituents on the para position of the phenyl moieties and ii) varying the metal centers [Pt(II) or Pd(II)] of the meso-tetrakisphenylporphyrins. A set of nanofibers; (Pt-TPP)NF, (Pd-TPP)NF, (Pt-TPA)NF and (Pd-TPA)NF were obtained to study their structure-activity relationship toward oxygen. The lifetime-based technique was privileged to take advantage of their long-lived phosphorescent properties. A two-fold enhancement was observed for (Pt-TPA)NF and (Pd-TPA)NF compared to (Pt-TPP)NF and (Pd-TPP)NF demonstrating the positive effect of the phenylacetylide moieties on the lifetime. Also, Silver nanoparticles were included in nanofibers to investigate their influence on lifetime-based oxygen sensitivity, showing that the presence of AgNPs only affects (Pd-TPA)NF.

Verbal and musical short-term memory: Variety of auditory disorders after stroke.

Auditory cognitive deficits after stroke may concern language and/or music processing, resulting in aphasia and/or amusia. The aim of the present study was to assess the potential deficits of auditory short-term memory for verbal and musical material after stroke and their underlying cerebral correlates with a Voxel-based Lesion Symptom Mapping approach (VLSM). Patients with an ischemic stroke in the right (N=10) or left (N=10) middle cerebral artery territory and matched control participants (N=14) were tested with a detailed neuropsychological assessment including global cognitive functions, music perception and language tasks. All participants then performed verbal and musical auditory short-term memory (STM) tasks that were implemented in the same way for both materials. Participants had to indicate whether series of four words or four tones presented in pairs, were the same or different. To detect domain-general STM deficits, they also had to perform a visual STM task. Behavioral results showed that patients had lower performance for the STM tasks in comparison with control participants, regardless of the material (words, tones, visual) and the lesion side. The individual patient data showed a double dissociation between some patients exhibiting verbal deficits without musical deficits or the reverse. Exploratory VLSM analyses suggested that dorsal pathways are involved in verbal (phonetic), musical (melodic), and visual STM, while the ventral auditory pathway is involved in musical STM.

Synthesis and Straightforward Quantification Methods of Imino Nitroxide-Based Hexaradical Architecture on a Cyclotriphosphazene Scaffold.

The synthesis of a homogeneous neutral hexaradical architecture consisting of six imino nitroxide radical moieties covalently bonded on a cyclotriphosphazene scaffold was reported. The synthesis of hexaradical imino nitroxide compounds follows the Ullman procedure involving the condensation of 2,3-bis(hydroxylamino)-2,3-dimethylbutane with hexa-(4-formylphenoxy)cyclotriphosphazene (3) followed by oxidation of the condensation product hexa-[4-(1-hydroxy-4,4,5,5-tetramethyl-2-imidazoline-2-yl)phenoxy]cyclotriphosphazene (2) by NaIO4. Characterization of hexaradical was performed by X-ray and SQUID in solid state and by EPR, absorption spectroscopy, and electrochemistry in solution. CV of 1 shows an oxidation peak at 1.184 V (vs SCE) and a reduction peak at -0.883 V, both characteristics of the presence of phenyl imino nitroxide (7) moieties, suggesting that the contribution of the cyclotriphosphazene core is negligible. Attention was particularly focused on developing methods, UV-vis spectroscopy and square-wave voltammetry, to quantify the number of radicals in a way to confirm easily and rapidly the polyradicals' structure.

Mechanism of the Zn(II)Phthalocyanines' Photochemical Reactions Depending on the Number of Substituents and Geometry.

In this work, the synthesis and the nonlinear absorption and population dynamics investigation of a series of zinc phthalocyanines (ZnPcs) dissolved in chloroform are reported. In order to determine the relevant spectroscopic parameters, such as absorption cross-sections of singlet and triplet excited states, fluorescence relaxation times, intersystem crossing, radiative decay and internal conversion, different optical and spectroscopic techniques were used. By single pulse and pulse train Z-scan techniques, respectively, singlet and triplet excited states' absorption cross-section were determined at 532 nm. Furthermore, the intersystem crossing time was obtained by using both techniques combined with the fluorescence lifetime determined by time-resolved fluorescence. The radiative and internal conversion rates were determined from the fluorescence quantum yield of the samples. Such spectroscopy parameters are fundamental for selecting photosensitizers used in photodynamic therapy, as well as for many other applications.

ABAB homoleptic bis(phthalocyaninato)lanthanide(III) complexes: original octupolar design leading to giant quadratic hyperpolarizability.

The octupolar cube, a Td symmetry cube presenting alternating charges at its corners, is the generic point charge template of any octupolar molecule. So far, transposition into real molecular structures has yet to be achieved. We report here a first step toward the elaboration of fully cubic octupolar architectures. A series of octupolar bis(2,3,16,17-tetra(hexylthio)phthalocyaninato)lanthanide double-decker complexes [Pc2Ln], Ln = Nd (1), Eu (2), Dy (3), Y (4), and Lu (5), are described, whose original three-dimensional structures display the required alternation of ABAB type for one face of the cube and the delocalization between the two rings approximating to the electronic interaction along the edges of the cube. Synthesis, X-ray crystal structure, and study of the optical properties and of the first molecular hyperpolarizability ß are reported. The size of the lanthanide (III) central ion modulates the ring-to-ring distance and the degree of coupling between the two phthalocyanine rings. As a consequence, the optical properties of these octupolar chromophores and in particular the strong near-infrared absorption due to the intervalence transition between the two rings also depend on the central lanthanide (III) ion. The first oxidized and reduced states of the complexes, while keeping a similar octupolar structure, display considerably changed optical properties compared to the neutral states. Second-order nonlinear properties were determined by nonpolarized harmonic light scattering in solution at 1907 nm. Exceptionally large dynamic molecular first hyperpolarizabilities √(<ßHLS(2)>1907), among the highest ever reported, were found that showed a strong dependence on the number of 4f electrons.

ABAB homoleptic bis(phthalocyaninato)lutetium(III) complex: toward the real octupolar cube and giant quadratic hyperpolarizability.

The concept of octupolar molecules has considerably enlarged the engineering of second-order nonlinear optical materials by giving access to 2D and 3D architectures. However, if the archetype of octupolar symmetry is a cube with alternating donor and acceptor groups at the corners, no translation of this ideal structure into a real molecule has been realized to date. This may be achieved by designing a bis(phthalocyaninato)lutetium(III) double-decker complex with a crosswise ABAB phthalocyanine bearing alternating electron-donor and electron-acceptor groups. In this communication, we present the first step toward this goal with the synthesis, crystal structure determination, and measurement of the molecular first-order hyperpolarizability ß by harmonic light diffusion, of an original lutetium(III) sandwich complex displaying the required ABAB-type alternation for one face of the cube. This structure is characterized by an intense absorption in the near-IR due to an intervalence transition and exhibits the highest quadratic hyperpolarizability ever reported for an octupolar molecule, √<ß(2)(HLS)> = 5750 × 10(-30) esu.

Nitroxide radicals appended to phthalonitriles: synthesis, structural characterization and photophysical properties.

The syntheses of 4-[4-(4,4,5,5-tetramethyl-2-imidazoline-3-oxide-1-oxyl-2-yl)phenoxy]phthalonitrile (3, C21H19N4O3) and 4-[4-(4,4,5,5-tetramethyl-2-imidazoline-1-oxyl-2-yl)phenoxy]phthalonitrile (4) were carried out by microwave-assisted nucleophilic aromatic substitution of 4-nitrophthalonitrile (2) by the pre-formed 2-(4-hydroxyphenyl)-4,4,5,5-tetramethyl-2-imidazoline-3-oxide-1-oxyl (1). Compounds 3 and 4 were characterized unambiguously by a rich array of analyses, such as melting point, FT-IR, MALDI-TOF MS, elemental analysis, UV-Vis, CV, EPR, magnetic measurements and single-crystal X-ray diffraction. Structural studies demonstrate that the C-H...X and C-X...π (X = O and N) interactions in the radical nitronyl nitroxide groups play an important role in the assembly of the crystal structures. Moreover, cyclic voltammetry analyses show that the phthalonitrile substituent retains the redox properties of the Ullman radicals.

Recognition of musical emotions and their perceived intensity after unilateral brain damage.

For the hemispheric laterality of emotion processing in the brain, two competing hypotheses are currently still debated. The first hypothesis suggests a greater involvement of the right hemisphere in emotion perception whereas the second hypothesis suggests different involvements of each hemisphere as a function of the valence of the emotion. These hypotheses are based on findings for facial and prosodic emotion perception. Investigating emotion perception for other stimuli, such as music, should provide further insight and potentially help to disentangle between these two hypotheses. The present study investigated musical emotion perception in patients with unilateral right brain damage (RBD, n = 16) or left brain damage (LBD, n = 16), as well as in matched healthy comparison participants (n = 28). The experimental task required explicit recognition of musical emotions as well as ratings on the perceived intensity of the emotion. Compared to matched comparison participants, musical emotion recognition was impaired only in LBD participants, suggesting a potential specificity of the left hemisphere for explicit emotion recognition in musical material. In contrast, intensity ratings of musical emotions revealed that RBD patients underestimated the intensity of negative emotions compared to positive emotions, while LBD patients and comparisons did not show this pattern. To control for a potential generalized emotion deficit for other types of stimuli, we also tested facial emotion recognition in the same patients and their matched healthy comparisons. This revealed that emotion recognition after brain damage might depend on the stimulus category or modality used. These results are in line with the hypothesis of a deficit of emotion perception depending on lesion laterality and valence in brain-damaged participants. The present findings provide critical information to disentangle the currently debated competing hypotheses and thus allow for a better characterization of the involvement of each hemisphere for explicit emotion recognition and their perceived intensity.

Effect of In-Hospital Remote Ischemic Perconditioning on Brain Infarction Growth and Clinical Outcomes in Patients With Acute Ischemic Stroke: The RESCUE BRAIN Randomized Clinical Trial.

Importance: Treatment with remote ischemic perconditioning has been reported to reduce brain infarction volume in animal models of stroke. Whether this neuroprotective effect was observed in patients with acute ischemic stroke remains unknown. Objective: To determine whether treatment with remote ischemic perconditioning administered to the leg of patients with acute ischemic stroke can reduce brain infarction volume growth. Design, Setting, and Participants: This proof-of-concept multicenter prospective randomized open-label with blinded end point clinical trial was performed from January 12, 2015, to May 2, 2018. Patients were recruited from 11 stroke centers in France. Of the 188 patients who received magnetic resonance imaging within 6 hours of symptom onset and were confirmed to have carotid ischemic stroke, 93 were randomized to receive treatment with lower-limb remote ischemic perconditioning in addition to standard care (the intervention group), and 95 were randomized to receive standard care alone (the control group). Interventions: Randomization on a 1:1 ratio to receive treatment with remote ischemic perconditioning (4 cycles of 5-minute inflations and 5-minute deflations to the thigh to 110 mm Hg above systolic blood pressure) in addition to standard care or standard care alone. Main Outcomes and Measures: The change in brain infarction volume growth between baseline and 24 hours, measured by a diffusion-weighted sequence of magnetic resonance imaging scans of the brain. Results: A total of 188 patients (mean [SD] age, 67.2 [15.7] years; 98 men [52.1%]) were included in this intention-to-treat analysis. At hospital admission, the median National Institutes of Health Stroke Scale score was 10 (interquartile range [IQR], 6-16) and the median brain infarction volume was 11.4 cm3 (IQR, 3.6-35.8 cm3); 164 patients (87.2%) received intravenous thrombolysis, and 64 patients (34.0%) underwent mechanical thrombectomy. The median increase in brain infarction growth was 0.30 cm3 (IQR, 0.11-0.48 cm3) in the intervention group and 0.37 cm3 (IQR, 0.19-0.55 cm3) in the control group (mean between-group difference on loge-transformed change, -0.07; 95% CI, -0.33 to 0.18; P = .57). An excellent outcome (defined as a score of 0-1 on the 90-day modified Rankin Scale or a score equal to the prestroke modified Rankin Scale score) was observed in 46 of 90 patients (51.1%) in the intervention group and 37 of 91 patients (40.7%) in the control group (P = .12). No significant differences in 90-day mortality were observed between the intervention and control groups (14 of 90 patients; Kaplan-Meier estimate, 15.8% vs 10 of 91 patients; Kaplan-Meier estimate, 10.4%, respectively; P = .45) or with symptomatic intracerebral hemorrhage (4 of 88 patients [4.5%] in both groups; P = .97). Conclusions and Relevance: In this study, treatment with remote ischemic perconditioning, during or after reperfusion therapies, had no significant effect on brain infarction volume growth at 24 hours after symptom onset. Trial Registration: ClinicalTrials.gov Identifier: NCT02189928.

Synthetic Access to a Pure Polyradical Architecture: Nucleophilic Insertion of Nitronyl Nitroxide on a Cyclotriphosphazene Scaffold.

An optimized nucleophilic synthetic approach featuring mild conditions and microwave energy was utilized to circumvent the classical Ullman procedure and access a polynitronyl nitroxide radical easily and in pure form. The simultaneous controlled introduction of preformed nitronyl nitroxide radicals on a cyclotriphosphazene core leads to a novel polyphosphazene monomer which is suitable for both n- and a p-type redox-active material in organic rechargeable batteries as demonstrated by electrochemistry. Additionally, absorption spectra and square-wave voltammetry were utilized to quantify the number of nitronyl nitroxide radical units on the cyclotriphosphazene scaffold.

Expeditious selective access to functionalized platforms of A(7)B-type heteroleptic lanthanide double-decker complexes of phthalocyanine.

A one-step method to access to functionalized heteroleptic lanthanide double-decker complexes of phthalocyanine of A7B-type is reported. This optimized statistical method led to two hydroxylated model europium complexes, one of which was further converted into its mesylated and azido derivatives.

Modulation of the electronic and spectroscopic properties of Zn(II) phthalocyanines by their substitution pattern.

Four isomerically pure octasubstituted zinc phthalocyanines with variations in the attachment atom and positions of the substituents were selected for a systematic investigation of the effect of the substitution pattern on their electronic and spectroscopic properties. Effects which were investigated are the position, the electron donating and withdrawing properties, and the donating force of the substituent. The results are discussed and interpreted based on theoretical and experimental determination of the orbital levels. This work allows us to highlight which substitution patterns are the most suitable considering different common applications of phthalocyanines.

pH-induced "off-on-off" type molecular switch behaviors of zinc and free tetraimidazophthalocyanines.

Herein, the design and synthesis of pH sensing fluorophores, zinc(II) tetraimidazophthalocyanine (Pc-1) and metal free tetraimidazophthalocyanine (Pc-2), which present "off-on-off" type molecular switches were described. Their pH sensing properties have been investigated in detail in dimethylsulfoxide in the pH range of 2.0-15.0. The respective three forms of the molecules: deprotonated, neutral and protonated, were characterized by absorption and emission spectra as well as apparent pKa values (Pc-1: pKa1 = 5.2 and pKa2 = 14.3, Pc-2: pKa1 = 4.9 and pKa2 = 13.8). The protonation/deprotonation stages of imidazole groups of Pc-1 and Pc-2 present fluorescence-based "off-on-off" type molecular switch properties.

Fluorescence and FTIR Spectra Analysis of Trans-A2B2-Substituted Di- and Tetra-Phenyl Porphyrins.

A series of asymmetrically substituted free-base di- and tetra-phenylporphyrins and the associated Zn-phenylporphyrins were synthesized and studied by X-ray diffraction, NMR, infrared, electronic absorption spectra, as well as fluorescence emission spectroscopy, along with theoretical simulations of the electronic and vibration structures. The synthesis selectively afforded trans-A2B2 porphyrins, without scrambling observed, where the AA and BB were taken as donor- and acceptor-substituted phenyl groups. The combined results point to similar properties to symmetrically substituted porphyrins reported in the literature. The differences in FTIR and fluorescence were analyzed by means of detailed density functional theory (DFT) calculations. The X-ray diffraction analysis for single crystals of zinc-containing porphyrins revealed small deviations from planarity for the porphyrin core in perfect agreement with the DFT optimized structures. All calculated vibrational modes (2162 modes for all six compounds studied) were found and fully characterized and assigned to the observed FTIR spectra. The most intense IR bands are discussed in connection with the generic similarity and differences of calculated normal modes. Absorption spectra of all compounds in the UV and visible regions show the typical ethio type feature of meso-tetraarylporphyrins with a very intense Soret band and weak Q bands of decreasing intensity. In diphenyl derivatives, the presence of only two phenyl rings causes a pronounced hypsochromic shift of all bands in the absorption spectra. Time-dependent DFT calculations revealed some peculiarities in the electronic excited states structure and connected them with vibronic bands in the absorption and fluorescence spectra from associated vibrational sublevels.

New spin-transition-like copper(II)-nitroxide species.

Novel copper(II)-nitroxide complexes exhibiting a spin-transition-like behavior have been prepared and characterized. They include meso, chiral, and racemic 2-(3-pyridyl)-nitronyl nitroxides differently substituted in positions 4 and/or 5 by ethyl groups and pyrimidyl nitroxides. Depending on the stoichiometry of the reaction, tetranuclear and binuclear complexes were obtained whose structures are cyclic. The tetranuclear species, which include two intracyclic and two exocyclic metal sites, are similar to the previously reported complex of the tetramethylated analogue, while the binuclear complexes involve only endocyclic metal ions and have uncoordinated N-oxyl groups. The tetranuclear complexes exist as two isomers depending on the temperature of crystallization: at room temperature, N-oxyl ligand coordination is axial-axial, while it is axial-equatorial at low temperature. Unexpectedly, this isomerism concerns N-oxyl bonding to the exocyclic metal centers for the derivatives of 4,5-diethyl-substituted ligands while it involves the endocyclic metal site in the complex of the monoethylated ligand, which converts reversibly from a high-spin state to a low-spin state, as observed for the complex of the tetramethylated ligand. Binuclear complexes are diamagnetic at room temperature but convert to a paramagnetic state on warming (90-110 degrees C); the transition is irreversible and sharp.

The cyano nitronyl nitroxide radical: experimental and theoretical evidence for the fourth case of the McConnell-I mechanism.

The nitronyl nitroxide 2-cyano-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (1) crystallises in the tetragonal P42(1)m space group with a=7.4050(7), c=8.649(1) A. In the crystal the molecules form layers parallel to the ab plane in which they are orthogonal to each other. In the layers there are close contacts, 2.953(2) A, between the NO groups and the bridging carbon atoms of the O-N-C-N-O fragment of neighbouring radicals. The calculated spin density shows a positive population mainly and equally localised on the NO groups and small but significant negative spin densities on the bridging carbon atom and the cyano nitrogen. Absorption spectra show temperature-dependent transitions related to the magnetic behaviour. The temperature dependence of the magnetic susceptibility in the range 2-300 K reveals that couplings between the radicals are antiferromagnetic, and is interpreted by considering a two-dimensional square array of spin S=1/2 antiferromagnetically coupled (J=-10 cm(-1) and g=2.01). This is interpreted as an exchange coupling through close contact between positive and negative spin densities in orthogonal orbitals on oxygen and carbon atoms, respectively.