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Yanshanian (ca. 200–100 Ma) metallogeny of eastern Asia was dominantly controlled by oblique subduction and rollback of the Izanagi plate, and also, more locally in the north, by closure of the Mudanjiang Ocean basin and accretion of the Bureya-Jiamusi-Khanka block and the Sikhote-Alin terranes. Although exact distances are difficult to estimate due to Early Cretaceous crustal extension, ores related to Yanshanian subduction certainly developed for more than 1500 km landward from the active trench, such as exemplified by those deposits overprinting the Paleoproterozoic Trans-North China orogen. In the northern part of the Yanshanian orogen, and thus hosted within the eastern edge of the Central Asian orogenic belt, Endako-type porphyry Mo deposits related to subduction of the Mudanjiang slab formed throughout northeast China from 200 to 135 Ma. Extensional magmatism related to rollback of the slab led to widespread Au-Ag epithermal vein development and a scattering of small Cu-Au porphyry occurrences across the same area from 125 to 100 Ma. Sinistral strike-slip motion along the continental margin in adjacent Russia, caused by the NNW motion of the Izanagi plate, led to formation of 115–95 Ma post-collisional Cu-Au porphyries, Sn-W ores associated with reduced intrusions, and orogenic gold deposits in the central Sikhote-Alin region. In the North China block, whereas early Yanshanian ore formation was relatively limited, 130–120 Ma extension-related basement uplifts were associated with formation of two of China’s most important orogenic gold provinces on the Jiaodong Peninsula and in the East Qinling; in the latter, the entire period of late Yanshanian extension may be defined by widespread 148–107 Ma Mo-rich porphyry and skarn deposit formation. To the south along the Asian margin, the oblique NW-directed subduction of the Izanagi slab was responsible for the adakitic porphyry Cu deposit formation on the eastern side of the South China block at 175–155 Ma, which continued inland for as much as 500 km to the Cathaysia-Yangtze suture. The transition at 160–150 Ma to development of the Nanling W-Sn belt in the interior of Cathaysia roughly overlaps the time of tectonic switch to slab retreat, which gradually led to seaward migration of the extension-related magmatism forming the 145–133 Ma Sn ores and 110–100 Ma high to low sulfidation epithermal deposits along the Southeast Coast belt. A period of sinistral strike-slip along the southern end of the Tan-Lu fault system was possibly responsible for a tear in the Izanagi plate and consequential S-type magmatism forming W porphyry-skarn ores of the Jiangnan belt at 145–133 Ma and I-type magmatism leading to Fe-Cu-Au skarns at the northern edge of the Yangtze block. In summary, the early Yanshanian of eastern Asia was dominated by widespread subduction-related porphyry Mo formation in the north and localized porphyry Cu formation to the south, followed by late Yanshanian development of world-class Au, Mo, Sn, and W resources during subsequent slab retreat, continental-scale extension, and strike-slip events along continental margin transform faults.

The effects of the newly synthesized covalent conjugates of water-soluble fullerene derivatives (WSFD) with xanthene dyes: polyanionic WSFD-fluorescein (1), polycationic WSFD-fluorescein (2), polyanionic WSFD-eosin (3), and polyanionic WSFD (4), polycationic WSFD (5), fluorescein (6) and eosin (7), on activity of the membrane-bound Ca2+-ATPase of the sarcoplasmic reticulum (SR Ca2+-ATPase) were studied. Compounds 1, 3, 4, 6, and 7 inhibit the hydrolytic function of the enzyme, the inhibition constants for these compounds are Ki=1.3×10-5 M (1), Ki=4.7×10-6 M (3), Ki=2.5×10-6 M (4), Ki=6.1×10-5 M (6), and Ki=5.8×10-6 M (7). The effects of compounds 3, 6, and 7 on the hydrolytic function of the enzyme is competitive; compounds 1 and 4 are noncompetitive. Polycationic WSFD fluorescein (2) and polycationic WSFD (5) do not affect ATP hydrolysis, but inhibit active Ca2+ transport in a concentration of 0.01 mM by 100±10 and 40±4%, respectively. Conjugates 1 and 3 completely inhibit the hydrolytic and transport functions of the enzyme in a concentration of 0.01 mM, and in a concentration of 0.001 mM inhibit active Ca2+ transport by 60±6 and 55±6% uncoupling the hydrolytic and transport functions of SR Ca2+-ATPases. The obtained results demonstrate a significant effect of the studied compounds on the active transmembrane transfer of Ca2+ and make it possible to predict the presence of antimetastatic and antiaggregatory activities of the studied compounds.

Using methods of absorption and fluorescence spectroscopy, we show that noncovalent complexes based on a water-soluble fullerene derivative and chlorin e6 dissolved either in water or in ethanol are formed as a result of electrostatic interactions. The formation of these complexes causes a red shift of the absorption spectrum of chlorin e6 and efficient quenching of the intensity of its fluorescence. The Stern–Volmer quenching constants of complexes in water and ethanol are 7.3 × 105 and 2 × 105 M–1, respectively. We show that, in an aqueous solution, the complex consists, on average, of one molecule of the water-soluble fullerene derivative and three dye molecules, whereas this ratio in ethanol is 1 : 1.

The effect of 10 racemic spirocyclic hydroxamic acids (CHA 1–10, derivatives of 1-hydroxy-1,4,8-triazaspiro[4,5]decan-2-one), containing pharmacophore imidazolidinone and piperidine fragments with different substituents, on the activity of enzyme histone deacetylase (HDAC) was studied. It was shown that CHA (1–10) inhibit HDAC activity in cultured breast cancer cells. It was shown that CHA (1–10) as a part of polychemotherapy with cisplatin and cyclophosphane have a pronounced chemosensitizing antitumor activity in vivo. The results obtained on tumor models in vivo showed that CHA can be considered as potential medicinal components of tumor polychemotherapy.

The synthesis, photophysical and photodynamic properties of two water-soluble hybrid structures based on the polycationic or polyanionic fullerene [60] derivative covalently linked to fluorescein are described. The significant influence of electrostatic charges on the conformation of the studied fullerene–fluorescein structures in aqueous solution and on their photophysical properties and photochemical activity was demonstrated. A polycationic fullerene derivative–fluorescein conjugate exhibits a pronounced quenching of fluorescence (more than 25 times) due to the energy and/or electron transfer from dye to fullerene. Such activation of fullerene generates reactive oxygen species greater than 15 times more effectively than an individual dye or fullerene does. In contrast, for the polyanionic fullerene derivative–fluorescein conjugate such effects are practically absent. The demonstrated effects open up wide opportunities for a directional design of highly efficient water-soluble photosensitizers by combining the singlet-excited dyes and fullerene [60] for applications in photodynamic therapy.

Synthesis, spectral properties, and photodynamic activity of water-soluble amino acid fullerene C

Free fluorescence spectra in solution and surface-enhanced Raman scattering (SERS) and surface enhanced fluorescence (SEF) spectra of chlorin e6 and water-soluble covalent fullerene–chlorin dyads have been studied. It has been demonstrated that chlorin e6 and covalent fullerene–chlorin dyads have similar characteristic SERS spectra. The fullerene–chlorin dyads show a pronounced SEF signal, while native chlorin e6 has no fluorescence on surface, which is consistent with the theory predicting an inverse dependence of the SEF intensity on the free fluorescence quantum yield. The concentration dependence of the SEF intensity is linear for the dyads in the range 0.1–2.0 μmol/L. These effects allow one to determine, with high sensitivity, the content of fullerene–chlorin dyads with a low quantum yield of free fluorescence in solutions, which opens wide opportunities for study of biological properties of fullerene–chlorin dyads and their applications in medicine.

The effect of iron nitrosyl complexes, NO donors, of a general formula [Fe2(L)2(NO)4] with functional sulfur-containing ligands (L-3-nitro-phenol-2-yl, 4-nitro-phenol-2-yl, or 1-methyl-tetrazol-5-yl) on the activity of sarcoplasmic reticulum Ca2+-ATPase and cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) was studied. The test complexes uncoupled the hydrolytic and transport functions of Ca2+- ATPase, thus disturbing the balance of Ca2+ ions in cells, which may affect the formation of thrombi and adhesion of metastatic cells to the endothelium of capillaries. They also inhibited the activity of cGMP PDE, thereby contributing to the accumulation of the second messenger cGMP. The studied iron nitrosyl complexes can be considered as potential drugs.

Synthesis, spectral properties, and photodynamic activity of water-soluble amino acid fullerene C60 derivatives (AFD) and four original AFD-PPa dyads, obtained by covalent addition of dye pyropheophorbide (PPa) to AFD, were studied. In aqueous solution, these AFD-PPa dyads form nanoassociates as a result of self-assembly. In this case, a significant change in the absorption spectra and strong quenching of the dye fluorescence in the structure of the dyads were observed. A comparison of superoxide or singlet oxygen generation efficiency of the studied compounds in an aqueous solution showed the photodynamic mechanism switching from type II (singlet oxygen generation of the native dye) to I type (superoxide generation of dyads). All dyads have pronounced phototoxicity on cells Hela with IC50 9.2 µM, 9.2 µM, 12.2 µM for dyads Val-C60-PPa, Ala-C60-PPa and Pro-C60-PPa, respectively. Such facilitation of type I photodynamic mechanism could be perspective against hypoxic tumors.

Chlorin e6 derivative and water-soluble dyad resulting from covalent bonding of polyanionic fullerene С60 derivative to chlorin e6 derivative were synthesized and studied for spectral properties and photochemical activity. A considerable change in the absorption spectra and pronounced fluorescence quenching for the chlorin moiety included in the dyad were identified. The singlet excited state of chlorin is quenched via electron transfer from the excited chlorin to the fullerene core. A comparison of the photochemical activities of the test compounds in aqueous solutions showed a tenfold increase in the photochemical activity of the chlorin–fullerene dyad compared with free chlorin per absorbed light quantum.

The effect of synthetic analogues of dinitrosyl mononuclear iron complexes (DNICs) with functional sulfur-containing ligands (NO donors) on the activity of myeloperoxidase (MPO) was studied, and their efficiency was evaluated. It was shown that the enzyme MPO is the molecular target of DNICs. It was found that six DNICs inhibited the activity of MPO and one compound potentiated it. The evaluation of their efficiency showed that two DNICs effectively inhibited the activity of MPO by 50% at IC50 = 2 × 10–4 M and IC50 = 5 × 10–7 M.

By the use of absorption spectroscopy, steady-state and time resolved fluorimetry xanthene dyes fluorescein, eosin Y and erythrosin B were shown to form complexes with polycationic fullerene derivative due to electrostatic interactions in aqueous solution and in the structure of the liposomes. It was found that the singlet excited states of dyes are effectively quenched either due to excitation energy transfer or electron transfer from singlet excited state of the dye to the fullerene core. Photodynamic activity of the complex is much higher than the activity of the dye or the fullerene derivative as the individual compounds. Photostability of the dyes increases in the complex structure as well. These effects allow predicting the development of a new generation hybrid photosensitizers. Noteworthy, one can use a dye excited only in a singlet state in combination with fullerene, which greatly enhances the directional design of such hybrid structures.

The effects of the newly synthesized covalent conjugates of water-soluble fullerene derivatives (WSFD) with xanthene dyes: polyanionic WSFD-fluorescein (1), polycationic WSFD-fluorescein (2), polyanionic WSFD-eosin (3), and polyanionic WSFD (4), polycationic WSFD (5), fluorescein (6) and eosin (7), on activity of the membrane-bound Ca

The effect of N-nitroxymethyl succinimide (1), N-(2-nitroxyethyl) succinimide (2) and N-(3-nitroxypropyl) succinimide (3) on enzymatic activity of cyclic guanosine monophosphate (cGMP) phosphodiesterase was studied and crystal structure of compound (2) was determined. It was shown that all studied N-nitroxy succinimides inhibited cGMP phosphodiesterase in a concentration range of 0.1-0.001 mM. Compound (2) noncompetitively and reversibly inhibited hydrolytic function of enzyme with Ki=1.7×10-5 М. Inhibition constant for the reference compound N-(2-nitroethyl) nicotinamide (nicorandil) was 3×10-5 М.

In magnetic compounds with Jahn–Teller (JT) ions (such as Mn3+ or Cu2+), the ordering of the electron or hole orbitals is associated with cooperative lattice distortions. There the role of JT effect, although widely recognized, is still elusive in the ground state properties. Here we discovered that, in these materials, there exist excitations whose energy spectrum is described in terms of the total angular momentum eigenstates and is quantized as in quantum rotors found in JT centers. We observed features originating from these excitations in the optical spectra of a model compound LaMnO3 using ellipsometry technique. They appear clearly as narrow sidebands accompanying the electron transition between the JT split orbitals at neighboring Mn3+ ions, displaying anomalous temperature behavior around the Neel temperature T N ≈ 140 K. We present these results together with new experimental data on photoluminescence found in LaMnO3, which lend additional support to the ellipsometry implying the electronic-vibrational origin of the quantum rotor orbital excitations. We note that the discovered orbital excitations of quantum rotors may play an important role in many unusual properties observed in these materials upon doping, such as high-temperature superconductivity and colossal magnetoresistance.

Using spectrophotometry and stationary and kinetic fluorimetry, we have shown that xanthene dye fluorescein forms complexes with polycationic derivative of fullerene in aqueous solutions mainly due to electrostatic interactions. It is found that efficient quenching of singlet excited states of dye occurs in the structure of these complexes due to the transfer of excitation or electron from dye to fullerene. As a result, the photodynamic activity of the newly formed complex is much higher than that of fluorescein and fullerene derivative. This effect makes it possible to predict the formation of new-generation hybrid photodynamic preparations using dyes excited only into a singlet state; as a result, directed searches for these dyes are significantly facilitated.

The potential of surface enhanced Raman spectroscopy (SERS) for the detection of water-soluble fullerene derivatives and their covalent conjugates with xanthene dyes was investigated in model biological liposome membranes and in the albumin protein structure. It was shown that in liposomes and in albumin, fullerene derivatives and their covalent conjugates with dyes show characteristic SERS spectra, which allows detection of water-soluble fullerene derivatives in phosphatidylcholine liposomes at the lipid/fullerene derivative ratio of 100 as well as fullerene–dye conjugates in liposomes and albumin.

The synthesis of water-soluble dyads PFD-Chl(1), PFD-Chl(Zn) and PFD-Chl(2) based on a polyanionic fullerene[60] derivative PFD covalently linked to chlorin e6 was described. Photophysical properties, generation of superoxide and singlet oxygen in water and liposomes, and photodynamic activity on HeLa cancer cells of obtained dyads were analyzed. The significant influence of linker length between fullerene[60] core and dye, presence of metal (Zn) atom in chlorin moiety on photophysical properties, and photodynamic activity of the dyads was demonstrated. All dyads exhibit quenching of chlorin fluorescence by 7–120 times due to the electron transfer from the dye to fullerene and they formed nanoassociates in aqueous solutions with an effective radius in the range of 30–500 nm due to their pronounced amphiphilic properties. Such nanoassociates were able to effectively interact with membranes of liposomes, which led to a sharp increase of fluorescence signal. This effect could be applied for the design of various fullerene-based nanoscale switch-off systems. The dyad PFD-Chl(1) – with the shortest linker and metal-free dye – had the superoxide generation efficiency 5.6 and 3.4 times higher compared to free chlorin Се6 in water and liposomes, respectively, while its singlet oxygen generation was reduced. The phototoxicity of this dyad in HeLa cells was almost equal to that of the native chlorin, despite the reduction of singlet oxygen generation efficiency. Upon the incorporation of zinc atom into a chlorin moiety of this dyad, photodynamic activity and phototoxicity of PFD-Chl(Zn) dyad became negligible. The PFD-Chl(2) dyad – with the longest linker and metal-free chlorin – had about two times lower photodynamic activity and phototoxicity compared to Ce6 due to weak interaction between fullerene core and the dye. A significant increase of the type I pathway efficiency, demonstrated in the PFD-Chl(1) dyad, could be applied for the creation of photosensitizers, highly effective against hypoxic tumors. The demonstrated approach opens up vast opportunities for a directional design of highly efficient fullerene-based water-soluble photosensitizers for photodynamic therapy.

The effect of iron nitrosyl complexes, NO donors, of a general formula [Fe

229 As known, fullerenes are photoexcited to a triplet state in 100% quantum yield, which then is deacti vated to generate, depending on the polarity of a medium, either singlet oxygen О2 or superoxide radi cal anions and other active radicals [1]. Numerous studies have addressed the photodynamic effect of fullerene and their derivatives: the generation of active radicals upon photoexcitation is responsible for dam age of DNA, proteins, and membranes, as well as for the suppression of the reproduction of tumor cells, viruses, and bacteria [2]. However, the efficiency of the photodynamic action of fullerenes and the pros pects for their application in medicine are essentially limited by the weak absorption by fullerenes of visible light, especially in the range 650–800 nm, which is most suitable for photodynamic therapy. The photodynamic effect of fullerenes can be con siderably enhanced by creating hybrid nanostructures − О2 . (HNSs) via the formation of a fullerene complex with a dye that efficiently absorbs visible light [3]. In such a complex, the dye can efficiently absorb light and transfer excitation energy or electron to the fullerene. Further excitation transfer or electron transfer from the fullerene to molecular oxygen will generate active oxygen species. The creation of such an HNS based on fullerene and a dye can thereby significantly enhance the efficiency of photodynamic therapy.

It has been shown by the use of steady-state and time-resolved fluorimetry and kinetic phosphorescent spectroscopy that a polycationic fullerene derivative forms complexes with eosine Y in solution due to electrostatic interactions. It has been found that singlet excited states of eosine Y are effectively quenched due to either the excitation energy transfer or electron transfer from the dye to the fullerene core. This leads to a substantial increase in the photodynamic activity of the fullerene derivative and the dye in the structure of the complex when it is excited by light in the absorption band of the dye.

The review briefly outlines theoretical models developed in 1990s to describe electron transfer reactions (ETR) in proteins, as well as different variants of improvements in these models proposed by the present authors to describe ETR in reaction centers (RC) of photosynthetic bacteria with consideration of their molecular dynamics in a wide temperature range. Experimental data on electron transfer from reduced proximal heme c-559 of cytochrome to bacteriochlorophyll dimer radical cation P+ in RC from two types of bacteria, viz., native and mutant RC from Rps. viridis and native RC from Rps. sulfoviridis were analyzed within the framework of the models which take into account the quantum and classical (including diffusive) degrees of freedom responsible for reorganization of the protein globule.

We studied the low-temperature dynamics of the Stokes shift of instantaneous phosphorescence spectra of eosin and eosin maleimide covalently bound to hemoglobin in a 66% v/v aqueous solution of glycerol under conditions of pulsed excitation. The kinetics of the Stokes shifts are described using the Cole-Davidson distribution function. From the experimental data, we obtain the parameters τ0 and β, which describe the Cole-Davidson distribution. Values of τ0 and β agree well with data obtained by other methods, and these parameters can be used to describe electron transfer reactions in polar solutions and proteins.

Kinetic curves of reduction of the oxidized bacteriochlorophyll dimer by the proximal heme of cytochrome in seven mutated reaction centers from Rps. viridis was measured in the temperature range of 295-10 K under an ambient potential when two high-potential hemes were reduced. The data are analyzed in frames of a model which accounts for slow medium dynamics (the diffusion-reaction equation) and the quantum effect in the modes responsible for reorganization of the cofactors and the medium. The model reproduces the observed nonexponential kinetics down to the lowest temperature where the fast kinetic component still survives. The modeling results in determination of an average characteristic time for re-orientation of dipoles of the protein matrix as a function of temperature. At temperatures above the glass-transition temperature, this function shows Arrhenius behavior with the activation energy varying between the values of 0.5 eV for wild type Rps. viridis and 0 eV for Rps. sulfoviridis found previously. Possible reasons for disappearance of the fast kinetic component in some reaction centers under study at low temperatures are discussed.

It has been shown that amino acid derivatives of C60 fullerene (ADFs) are effective quenchers of phosphorescence of the triplet probes eosin and erythrosine. The rate constants of erythrosine phosphorescence quenching by ADFs in aqueous solutions and model membranes have been determined. Using the triplet probe technique, the ability of ADFs to be transported across the lipid bilayer into the inner space of liposomes have been revealed. By monitoring a change in the fluorescence intensity of a luminescent hybrid structure based on C60-proline and eosin, the distribution of the hybrid structure in animal organs was established. The stability of hybrid structures subjected to various chemical and biological impacts was studied by recording the fluorescence of a Gd@C82-based hybrid structure.

The dynamic properties of isobutanol are studied in a wide (90–350 K) temperature range by recording the relaxation shifts in the steady-state luminescence spectra of eosin and erythrosine and by kinetic phosphorescent spectroscopy invoking the Cole-Davidson model for dielectric relaxation. The characteristic dipole relaxation times and the activation energy of relaxation processes in the matrix in the temperature range of 140–170 K are determined from the correlation function of the dynamic Stokes shift of the phosphorescence spectrum of luminescent probe molecules.

Electron transfer (ET) in the reaction center from Rhodopseudomonas viridis has been studied experimentally by our group in the range of temperatures of 153–295 K. The kinetics of ET reaction from the proximal heme of cytochrome to the special pair was found to be non-exponential. The degree of non-exponentiality strongly depends on temperature, with increasing non-exponentiality at lower temperatures. Here, the experimental kinetic data for ET are analyzed in the frames of a theoretical Sumi–Marcus-type model, which allows establishing a connection between the observed kinetics and local structural dynamics of the protein in a close vicinity of the donor and acceptor sites. The phenomenological model subdivides the multi-time-scale dynamics of the protein into two groups: fast and slow. The division is determined by the rate of ET, which is dynamically controlled by the slow modes of the protein medium. The slow modes are described by a phenomenological collective coordinate , for which a diffusion type ...

Structural data on the nitrogenase complex of Azotobacter vinelandii, Av1·(Av2)2, stabilized by MgADP·AlF4− and, in particular, the structure and properties of a P-cluster involved in the nitrogenase ATPase reaction, were analyzed. The ATP-binding site and all nitrogenase metal clusters are arranged in one plane, the distances between the closest partners being 14–15 A. The ATP-binding site in the Fe-protein, which decreases the half-reduction potential (Em) of the [4Fe-4S]-cluster in Av2 to −0.43 V, does not affect the potentials of the P-cluster and Fe-Mo cofactor (FeMoco). Amino acids 74–95 in the β-subunit of Av1 “envelop” the P-cluster in Av1; therefore, the phosphate intermediate of the ATPase reaction of nitrogenase occurs apparently in the direct contact with the P-cluster. By increasing the acceptor properties of the P-cluster, this intermediate may favor the electron transfer from the Fe-protein to the P-cluster, thus bringing it into the super-reduced state.

Here we report the investigation of photophysical properties and photodynamic action of two novel water soluble hybrid molecular structures based on [60]fullerene dyads bearing covalently attached residues of anthracycline antibiotic "ruboxyl". Molecular structures of the designed compounds were confirmed by IR and UV-VIS absorption spectroscopy, electrospray mass spectrometry (compound 5), and (1)H and (13)C NMR spectroscopy. Dynamic light scattering, steady-state and kinetic fluorimetry and UV-VIS absorption spectroscopy techniques were used to study the behavior of the synthesized hybrid molecular structures in aqueous solutions. Photodynamic activity of the compounds was evaluated by monitoring the O2(-) generation under visible light irradiation using the NBT test. It has been shown that the anthracycline chromophore (ruboxyl moiety possesses no photodynamic activity) behaves as an efficient photosensitizer for the fullerene core operating via the energy and/or the electron transfer pathways. The presented approach opens up wide opportunities for the design of various fullerene-based donor-acceptor systems with enhanced photodynamic properties potentially suitable for biomedicinal applications.