Andrei V. Cheprakov

Dendritic Phosphorescent Probes for Oxygen Imaging in Biological Systems

Oxygen levels in biological systems can be measured by the phosphorescence quenching method using probes with controllable quenching parameters and defined biodistributions. We describe a general approach to the construction of phosphorescent nanosensors with tunable spectral characteristics, variable degrees of quenching, and a high selectivity for oxygen. The probes are based on bright phosphorescent Pt and Pd complexes of porphyrins and symmetrically pi-extended porphyrins (tetrabenzoporphyrins and tetranaphthoporphyrins). pi-Extension of the core macrocycle allows tuning of the spectral parameters of the probes in order to meet the requirements of a particular imaging application (e.g., oxygen tomography versus planar microscopic imaging). Metalloporphyrins are encapsulated into poly(arylglycine) dendrimers, which fold in aqueous environments and create diffusion barriers for oxygen, making it possible to regulate the sensitivity and the dynamic range of the method. The periphery of the dendrimers is modified with poly(ethylene glycol) residues, which enhance the probes solubility, diminish toxicity, and help prevent interactions of the probes with the biological environment. The probes parameters were measured under physiological conditions and shown to be unaffected by the presence of biomacromolecules. The performance of the probes was demonstrated in applications, including in vivo microscopy of vascular pO(2) in the rat brain.

NC-palladacycles as highly effective cheap precursors for the phosphine-free Heck reactions

Eight cyclopalladated complexes of the formula [Pd2(μ-L)2(NC)2] (L=OAc, Cl; NC=cyclometalled N donor: o-(2-pyridyl)phenyl, o-(2-pyridyloxy)phenyl, o-(2-pyridylmethyl)phenyl, o-(N,N-dimethylaminomethyl)phenyl, 8-quinolylmethyl and others) and a six-membered palladacycle with OC coordination (ligand related to 2-acetoamido-4-nitrophenyl), are highly efficient catalysts for the Heck arylation of olefins (styrene, ethyl acrylate) by aryl halides (iodobenzene, bromobenzene, 4-bromoacetophenone). These catalysts are air stable, easy to obtain from a vast number of readily available nitrogen containing molecules, are generally much cheaper than phosphine-ligated palladacycles, but as or more efficient than the latter. Turnover numbers (ton) of up to 4 100 000 and turnover frequencies (tof) up to 530 000 are achieved in the reaction of iodobenzene with ethyl acrylate. Bromobenzene undergoes the Heck reaction (ton=400–700; tof=5–30) in the presence of the promoter additive Bu4NBr. The palladacycles are likely to operate in a common phosphine-free Pd(0)/Pd(II) catalytic cycle, while the differences between various types of palladacycle precursors are accounted for by the kinetics of the catalyst preactivation step.

Upconversion with ultrabroad excitation band: Simultaneous use of two sensitizers

The authors demonstrate the ability to combine sensitizers effectively working with single emitter in order to increase the excitation window for noncoherent upconversion. They show effective upconversion of the red part of the sun spectrum realized by ultralow excitation intensity (as low as 1Wcm−2) and ultrabroad excitation spectrum (Δλ∼80nm).

Towards the IR Limit of the Triplet-Triplet Annihilation-Supported Up-Conversion: Tetraanthraporphyrin

The processes by which locally (or in situ) up-converted photons are generated by NIR or IR excitation sources have been very intensively studied and have remarkable application potential in fields like up-conversion displays, biological imaging and sensing, and photodynamic therapy of cancer. The blue-shifted emission generated in the known and long-time studied up-conversion processes results from either two-photon absorption (TPA) in organic molecules, quantum dots or in proximity of metallic clusters, or sequential energy transfer (ETU) in rare-earth ion-doped glasses. All these processes have a common characteristic: they need an excitation source with very high brightness—in the case of TPA-based processes because of the virtual energy level used, in the case of the ETU-based processes because of the finite width of the ionic energy levels used. Additionally, both these processes need moderate or strong optical pumping, normally in order of many kWcm 2 up to MWcm . Recently, a different approach for up-conversion (UC), based on energetically conjoined triplet–triplet annihilation (TTA) was demonstrated. The fundamental advantage of the TTA-supported UC is its inherent independence on the coherence of the excitation light. The TTA-supported UC resolves also another demanding limitation of the above described “conventional” methods for UC (e.g., the ETU and all types of TPA)—the necessity to excite the samples with extremely bright optical sources (e.g., lasers). In contrast, for excitation of an efficient TTA–UC, optical sources with spectral power density of 125 mWnm 1 are sufficient and, in particular, the excitation source can be the Sun. The next advantage revealing the enormous application potential of the energetically conjoined TTA–UC is the very low intensity needed (on the order of 100 mWcm ) to achieve high quantum yields, on the order of 2–4% in organic solutions. In a further step, the efficiency of the TTA–UC in bulk solid-state films, composed of the sensitizer and emitter molecules blended in inactive polymer matrix, has to be optimized as it is significantly lower than in solutions. The TTA-supported up-conversion devices, based on organic solutions are very efficient, but cannot be easily sealed for the long term. The solid-state devices of this kind can be sealed easily, but they are not efficient enough. This obstacle can be avoided when highly viscous matrices are used. In fact, the energetically conjoined TTA–UC in highly viscous matrices possesses all the required characteristics: high quantum yield (comparable with those in liquid organic solution of the active species), very low excitation intensity ( 25 mWcm ), extremely low spectral power density optical sources ( 200 mWnm ), and versatility in excitation and emission wavelengths. These devices can be also sealed easily. The combination of all these unique characteristics and possibilities make energetically conjoined TTA–UC ready for diverse applications, such as all-organic, flexible, and transparent displays, up-converter devices for increasing the efficiency of, for example, dye-sensitized solar cells and local, in situ, generator of blue-shifted photons. To explore the above describe applications in their full, the IR limit, that is, the lowest energy photons able to serve as pumping source for the studied energetically conjoined TTA is of crucial importance. The highest excitation wave[a] Dr. V. Yakutkin, Dr. S. Baluschev Max-Planck-Institute for Polymer Research Ackermannweg 10, 55128 Mainz (Germany) Fax: (+49)6131-379-100 E-mail : balouche@mpip-mainz.mpg.de [b] S. Aleshchenkov, S. Chernov, Dr. A. Cheprakov Department of Chemistry, Moscow State University 119899 Moscow (Russia) Fax: (+7)495-939-1854 E-mail : avchep@elorg.chem.msu.ru [c] Dr. T. Miteva, Dr. G. Nelles Sony Deutschland GmbH Materials Science Laboratory, Hedelfingerstr. 61 70327 Stuttgart (Germany) Fax: (+49)711-5858-484 E-mail : miteva@sony.de Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200801305.

Effects of Structural Deformations on Optical Properties of Tetrabenzoporphyrins: Free-Bases and Pd Complexes

A recently developed method of synthesis of pi-extended porphyrins made it possible to prepare a series of tetrabenzoporphyrins (TBP) with different numbers of meso-aryl substituents. The photophysical parameters of free-bases and Pd complexes of meso-unsubstituted TBPs, 5,15-diaryl-TBPs (Ar2TBPs) and 5,10,15,20-tetraaryl-TBPs (Ar4TBPs) were measured. For comparison, similarly meso-arylsubstituted porphyrins fused with nonaromatic cyclohexeno-rings, i.e. Ar(n)-tetracyclohexenoporphyrins (Ar(n)TCHPs, n = 0, 2, 4), were also synthesized and studied. Structural information was obtained by ab initio (DFT) calculations and X-ray crystallography. It was found that: 1) Free-base Ar4TBPs are strongly distorted out-of-plane (saddled), possess broadened, red-shifted spectra, short excited-state lifetimes and low fluorescence quantum yields (tau(fl) = 2-3 ns, phi(fl) = 0.02-0.03). These features are characteristic of other nonplanar free-base porphyrins, including Ar4TCHPs. 2) Ar2TBP free-bases possess completely planar geometries, although with significant in-plane deformations. These deformations have practically no effect on the singlet excited-state properties of Ar2TBPs as compared to planar meso-unsubstituted TBPs. Both types of porphyrins retain strong fluorescence (tau(fl) = 10-12 ns, phi(fl) = 0.3-0.4), and their radiative rate constants (k(r)) are 3-4 times higher than those of planar H2TCHPs. 3) Nonplanar deformations dramatically enhance nonradiative decay of triplet states of regular Pd porphyrins. For example, planar PdTCHP phosphoresces with high quantum yield (phi(phos) = 0.45, tau(phos) = 1118 micros), while saddled PdPh4TCHP is practically nonemissive. In contrast, both ruffled and saddled PdAr(n)TBPs retain strong phosphorescence at ambient temperatures (PdPh2TBP: tau(phos) = 496 micros, phi(phos) = 0.15; PdPh4TBP: tau(phos) = 258 micros, phi(phos) = 0.08). It appears that pi-extension is capable of counterbalancing deleterious effects of nonplanar deformations on triplet emissivity of Pd porphyrins.

π-Extended Dipyrrins Capable of Highly Fluorogenic Complexation with Metal Ions

The synthesis and properties of a new family of pi-extended dipyrrins capable of forming brightly fluorescent complexes with metal ions are reported. The metal complexes possess tunable spectral bands and exhibit different emission properties depending on the mode of metal coordination.

Highly Non-Planar Dendritic Porphyrin for pH Sensing: Observation of Porphyrin Monocation

Metal-free porphyrin-dendrimers provide a convenient platform for the construction of membrane-impermeable ratiometric probes for pH measurements in compartmentalized biological systems. In all previously reported molecules, electrostatic stabilization (shielding) of the core porphyrin by peripheral negative charges (carboxylates) was required to shift the intrinsically low porphyrin protonation pK(a)s into the physiological pH range (pH 6-8). However, binding of metal cations (e.g., K(+), Na(+), Ca(2+), Mg(2+)) by the carboxylate groups on the dendrimer could affect the protonation behavior of such probes in biological environments. Here we present a dendritic pH nanoprobe based on a highly non-planar tetraaryltetracyclohexenoporphyrin (Ar(4)TCHP), whose intrinsic protonation pK(a)s are significantly higher than those of regular tetraarylporphyrins, thereby eliminating the need for electrostatic core shielding. The porphyrin was modified with eight Newkome-type dendrons and PEGylated at the periphery, rendering a neutral water-soluble probe (TCHpH), suitable for measurements in the physiological pH range. The protonation of TCHpH could be followed by absorption (e.g., ε(Soret)(dication)∼270,000 M(-1) cm(-1)) or by fluorescence. Unlike most tetraarylporphyrins, TCHpH is protonated in two distinct steps (pK(a)s 7.8 and 6.0). In the region between the pK(a)s, an intermediate species with a well-defined spectroscopic signature, presumably a TCHpH monocation, could be observed in the mixture. The performance of TCHpH was evaluated by pH gradient measurements in large unilamellar vesicles. The probe was retained inside the vesicles and did not pass through and/or interact with vesicle membranes, proving useful for quantification of proton transport across phospholipid bilayers. To interpret the protonation behavior of TCHpH we developed a model relating structural changes on the porphyrin macrocycle upon protonation to its basicity. The model was validated by density functional theory (DFT) calculations performed on a planar and non-planar porphyrin, making it possible to rationalize higher protonation pK(a)s of non-planar porphyrins as well as the easier observation of their monocations.

Synthesis of 5,15-Diaryltetrabenzoporphyrins

A general method of synthesis of 5,15-diaryltetrabenzoporphyrins (Ar 2TBPs) has been developed, based on 2 + 2 condensation of dipyrromethanes followed by oxidative aromatization. Two pathways to Ar 2TBPs were investigated: the tetrahydroisoindole pathway and the dihydroisoindole pathway. In the tetrahydroisoindole pathway, precursor 5,15-diaryltetracyclohexenoporphyrins (5,15-Ar 2TCHPs) were assembled from cyclohexeno-fused meso-unsubstituted dipyrromethanes and aromatic aldehydes or, alternatively, by way of the classical MacDonald synthesis. In the first case, scrambling was observed. Aromatization by tetracyclone was more effective than aromatization by DDQ but failed in the cases of porphyrins with electron-withdrawing substituents in the meso-aryl rings. The dihydroisoindole pathway was found to be much superior to the tetrahydroisoindole pathway, and it was developed into a general preparative method, consisting of (1) the synthesis of 4,7-dihydroisoindole and its transformation into meso-unsubstituted dipyrromethanes, (2) the synthesis of 5,15-diaryloctahydrotetrabenzoporphyrins (5,15-Ar 2OHTBPs), and (3) their subsequent aromatization by DDQ. Ar 2TBP free bases exhibit optical absorption spectra similar to those of meso-unsubstituted tetrabenzoporphyrins and fluoresce with high quantum yields. Pd complex of Ph 2TBP was found to be highly phosphorescent at room temperature.

Palladium catalyzed carbonylation of iodoarenes in aqueous solubilized systems

Abstract Iodobenzene and substituted iodobenzenes can be easily carbonylated into benzoic acids under mild conditions, with simple palladium salts as catalysts and normal pressure of CO, by using aqueous microemulsions of the oil-in-water kind as the reaction media. Surfactants of all three kinds, anionic, nonionic, and cationic, and simple aliphatic alcohols can be used to form the microemulsion media for carbonylation. The use of nonionic surfactants, the derivatives of polyethyleneglycol, is the most advantageous method as the surfactant is highly efficient in small amounts without a cosurfactant because of its strong solubilizing ability.

The dihydroisoindole approach to linearly annelated π-extended porphyrins

The dihydroisoindole strategy for the synthesis of linearly annelated π-extended porphyrins is a common approach to tetrabenzo-, tetranaphtho-, and tetraanthraporphyrins with variable functionality and substitution patterns. This method implies the use of a common type of precursors involving the 4,7-dihydroisoindole moiety, which are the closest possible stable relatives of the unstable isoindole, benzoisoindole and naphthoisoindole. A key feature of this strategy is the unprecedented mildness of the final oxidative aromatization step, which accounts for synthetic versatility, better functional group tolerance and high purity of the products. Many new linearly annelated π-extended porphyrins of the tetrabenzo-, tetranaphtho-, and tetraanthraporphyrin families were produced and characterized for the first time, including soluble planar and highly emissive 5,15-diaryl derivatives. The double bond of the dihydroisoindole fragment can also be useful for further modification of the porphyrin by means of addition of cycloaddition reactions, leading to new, previously inaccessible porphyins bearing multiple halide, hydroxy, or acetoxy groups at the periphery.