HP Complexes Research Articles

Enzymatic response of heparin-protamine complex: Spectroscopic investigation and application for lung adenocarcinoma cells detection

Though the heparin-protamine complex (HP complex) is a crucial system utilized in clinical settings, the metabolic pathways of this complex remain inadequately understood. Herein, the enzymatic degradation of the heparin-protamine complex by trypsin and its broader implications were investigated. By utilizing fluorescent gold nanoclusters liganded with the HP complex (AuNCs-HP complex), we observed significant morphological and spectral changes during enzymatic degradation. Experiments showed that AuNCs-HP complex could be degraded and cleaved into small fragments by trypsin. Moreover, the AuNCs-HP complex demonstrated its potential as a highly sensitive spectral sensing platform, enabling precise measurement of trypsin activity with an outstanding detection limit (0.34 ng mL−1). Additionally, we explored its utility for specific tumor cell detection, focusing on lung adenocarcinoma cells, and successfully identified their presence through distinctive fluorescence changes. These remarkable findings not only contribute valuable insights into targeted degradation systems but also offer promising opportunities for cancer biomarker detection. The AuNCs-HP complex serves as an innovative tool for real-time trypsin activity monitoring, paving the way for advanced biomedical applications.

Differential Fluid Activity in a Single Exhumed Continental Subduction Unit from Local P-T-M(H2O) Records of Zoned Amphiboles (North Muya, Eastern Siberia)

The behavior of the continental lithosphere in the Alpine-type subduction zones, which primarily depends on its thickness, thermal regime of subduction and availability of fluids/melts, remains an important issue for both metamorphic petrology and geochemistry as well as for resolving the thermomechanical properties of subduction paleo-interfaces. Rehydrated (amphibole- and zoisite-bearing) eclogites from the Neoproterozoic North Muya high-pressure complex (northern Central Asian Orogenic belt, eastern Siberia) were studied in order to assess their peak burial depths, degree of prograde dehydration, and further retrograde hydration extent within a subducted and exhumed continental unit. Three medium-grained eclogites from different localities of HP complex show similarly dry peak assemblages of pyrope-almandine-grossular garnet (XGrs up to 0.30, XPrp up to 0.25) + Na-rich omphacite (up to 44 mol % of jadeite) + rutile + quartz, which are variably replaced by secondary plagioclase + clinopyroxene ± amphibole symplectitic aggregate. The eclogites were subjected to burial at similar peak depths (up to ~17–21 kbar) but different peak temperatures (within ~600–730 °C) with or without notable heating and re-equilibration due to crustal thickening. Variable degrees of exhumation-induced pervasive rehydration led to growth of individual zoned porphyroblastic barroisite-hornblende amphibole ([B]Na = 0.03–0.45) ± zoisite over the primary eclogitic assemblage or after notable thermally-driven development of symplectitic aggregate after omphacite. Amphibole compositions together with the zoisite presence/absence in different samples reflect continuous rehydration by addition of ~0.5–1.5 wt.% at different exhumation conditions, from nearly peak eclogitic P–T (~17–21 kbar) to granulite- and amphibolite-facies depths within the plagioclase stability field (<14 kbar). This diversity most likely required irregular distribution of internally sourced, low-volume, hydrous metamorphic fluid (i.e., from host felsic rocks or metasediments) acting at different depths of the subduction interface. From the performed PTX calculations, I suggest that nearly isochemical (i.e., without any significant modification of the bulk-rock composition other than incorporation of additional H2O), retrograde hydration by only at lower- to middle-crust conditions did not significantly influence the density and the rheology of the subducted continental slices due to both (1) a limited abundance of dense metabasic rocks, which are commonly more fluid-rich (e.g., due to chlorite or amphibole alteration), and (2) the initially dry nature of mafic and felsic continental rocks. The limited dehydration and rehydration scales exemplified by the North Muya eclogites and therefore low availability of hydrous metamorphic fluids may have accounted for the high buoyancy of the eclogitic crust and explained the absence of contemporaneous suprasubduction magmatism in the regional context at ca. ~630 Ma.

Quantum chemical study of hydrogen-bonded complexes of serine with water and $$\hbox {H}_{2}\hbox {O}_{2}$$ H 2 O 2

Abstract The hydrogen bonded complexes of serine with water and with \(\hbox {H}_{2}\hbox {O}_{2}\) (HP) have been completely investigated in the present study using second-order Møller-Plesset perturbation theory (MP2) and density functional theory (DFT) in order to determine their geometries, stabilization energies, vibrational frequencies and electronic characteristics. The stabilization energies (\(\Delta \hbox {E}_{\mathrm{BSSE}})\) span a range of −2.76 to −12.46 kcal/mol for 1:1 serine–water complexes and −4.54 to −12.73 kcal/mol for 1:1 serine–HP complexes. The \(\Delta \hbox {E}_{\mathrm{BSSE}}\) values suggest that serine–HP complexes are more stable than serine–water complexes. For all the structures, complex formation results in elongation of N-H, O-H bonds and shortening of C-H bonds thereby showing the red-shift and blue-shift for the respective bonds. The structural, vibrational and electronic features are in accordance with the fact that HP is a better proton donor and water a better proton acceptor. The excellent relationship is obtained for the variation of \(\Delta \hbox {E}_{\mathrm{BSSE}}\) values with the sum of the \(\uprho \) values and the sum of laplacian at the BCPs for the HBs. The \(\hbox {E}^{(2)}\) values are also in concordance with the calculated \(\Delta \hbox {E}_{\mathrm{BSSE}}\) values. Graphical Abstract Synopsis Hydrogen-bonded serine–water and serine-Hydrogen Peroxide (HP) complexes have been extensively studied using quantum chemical methods. The nature of interactions exhibited by these complexes has been explored on the basis of analysis of geometrical data, stabilization energies, vibrational frequencies, AIM, NBO and SAPT studies.

Physicochemical characterization of ferumoxytol, heparin and protamine nanocomplexes for improved magnetic labeling of stem cells

Stem cell-based therapies have become a major focus in regenerative medicine and to treat diseases. A straightforward approach combining three drugs, heparin (H), protamine (P) with ferumoxytol (F) in the form of nanocomplexes (NCs) effectively labeled stem cells for cellular MRI. We report on the physicochemical characteristics for optimizing the H, P, and F components in different ratios, and mixing sequences, producing NCs that varied in hydrodynamic size. NC size depended on the order in which drugs were mixed in media. Electron microscopy of HPF or FHP showed that F was located on the surface of spheroidal shaped HP complexes. Human stem cells incubated with FHP NCs resulted in a significantly greater iron concentration per cell compared to that found in HPF NCs with the same concentration of F. These results indicate that FHP could be useful for labeling stem cells in translational studies in the clinic.

Cambrian to Lower Ordovician complexes of the Kokchetav Massif and its fringing (Northern Kazakhstan): Structure, age, and tectonic settings

A comprehensive study of the Lower Palaeozoic complexes of the Kokchetav Massif and its fringing has been carried out. It has allowed for the first time to discover and investigate in detail the stratified and intrusive complexes of the Cambrian–Early Ordovician. Fossil findings and isotope geochronology permitted the determination of their ages. The tectonic position and internal structures of those complexes have also been defined and their chemical features have been analyzed as well. The obtained data allowed us to put forward a model of the geodynamic evolution of Northern Kazakhstan in the Late Ediacaran–Earliest Ordovician. The accumulation of the oldest Ediacaran to Earliest Cambrian siliciclastics and carbonates confined to the Kokchetav Massif and its fringing occurred in a shallow shelf environment prior to its collision with the Neoproterozoic Daut island arc: complexes of the latter have been found in the northeast of the studied area. The Early Cambrian subduction of the Kokchetav Massif under the Daut island arc, their following collision and exhumation of HP complexes led to the formation of rugged ground topography, promoting deposition of siliceous–clastic and coarse clastic units during the Middle to early Late Cambrian. Those sediments were mainly sourced from eroded metamorphic complexes of the Kokchetav Massif basement. At the end of the Late Cambrian to the Early Ordovician within the boundaries of the massif with the Precambrian crust, volcanogenic and volcano-sedimentary units along with gabbros and granites with intraplate affinities were formed. Simultaneously in the surrounding zones, which represent relics of basins with oceanic crust, N-MORB- and E-MORB-type ophiolites were developed. These complexes originated under extensional settings occurred in the majority of the Caledonides of Kazakhstan and Northern Tian Shan. In the Early Floian Stage (Early Ordovician) older heterogeneous complexes were overlain by relatively monotonous siliceous–clastic units, that were being deposited until the Middle Darrivilian Stage (Middle Ordovician).

HP complex is not an essential hibernation switch

Switching off for winter is not easy. Only a select few species dramatically reduce their metabolism and hibernate to endure the long dark months, and how this remarkable tactic came about is not clear. ‘The evolutionary origin [of hibernation] is completely unknown’, says William Wong from

Geodynamic significance of preserved Carboniferous subduction complex in Atbashi range (South Tianshan, Kyrgyzstan) and inferences for crustal-scale structure of north Tarim-Tibet orogenic system

A subduction complex of carboniferous age is preserved in the South Tianshan belt of Kyrgyzstan. It is made of a LP-LT accretionnary prism comprising an obducted ophiolite thrusted by a HP complex made of a sedimentary channel including eclogites boudins and a continental unit. Its structure and metamorphic history are investigated to reconstruct the geodynamic evolution of the northern Tarim in the Upper Palaeozoic. This study gives insights into the crustal-scale structure of this mountain belt, currently intensely reactivated by the India-Asia collision. Eclogites boudins have a N-MORB type composition similar to the unmetamorphosed obducted ophiolite sequence. Evidence for eclogite facies in both acidic and mafic lithologiesand geological structure are in agreement with a deep subduction channel mainly comprised of metasediments. Eclogites boudins are investigated for a preliminary PT study. Prograde stage (I) begins in blue-schist/eclogite facies transition at 520 ± 30°C - 17 ± 1 kbar. Condit ions of peak metamorphism (II) in eclogite facies range from 550 ± 30°C - 18.5 ± 1 kbar to 540- 595°C - 21 kbar. Retrograde stage (III) is also in the eclogite facies conditions at 515 ± 30°C - 16.7 ± 1 kbar. The geological structure and metamorphic conditions of this suture zone implies the subduction of a narrow oceanic basin in a south-dipping subduction zone, while another north-dipping subduction was active below Middle Tianshan. Final stacking of Middle and South Tianshan occurred at 320-310 Ma. These antithetic subduction zones are still reflected in the main structures of Tianshan. Reactivation of the south­ dipping structures since 30 Ma is ascribed to explain the current localisation of uplift and deformation.

The Alps 1: A working geodynamic model for burial and exhumation of (ultra)high-pressure rocks in Alpine-type orogens

Eocene (ultra)high-pressure ((U)HP) rocks exposed in the Western Alps are generally interpreted to result from subduction of European continental crust beneath Adria and its subsequent exhumation. However, the roles of extension (either from plate divergence or internal to the orogen) and erosion during exhumation remain controversial. Here we use 2D numerical geodynamic models to explain the formation and exhumation of (U)HP rocks in an Alpine-type orogen and interpret the results in the conceptual Prowedge–Uplifted Plug–Retrowedge–Conduit (PURC) framework. (U)HP metamorphism of oceanic and microcontinent crust in the models results from burial and accretion to a subduction channel/conduit formed beneath an advancing retrocontinent. Rapid exhumation from (U)HP conditions is achieved by the buoyancy-driven transport of a composite plume of stacked (U)HP oceanic and microcontinent crust from the subduction conduit to the overlying orogenic prowedge, accommodated by coeval thrusting and normal-sense shearing. Subsequent ‘trans-crustal’ exhumation is achieved by a combination of doming/internal extension and later retrotransport of the (U)HP plume through the uplifted plug, during underthrusting of the thick continental margin crust, coupled with increased erosion. Our proposed mechanism implies that exhumation-related normal-sense shearing in the Western Alps, per se, was driven from below by the buoyancy of the ascending plume, and that extension owing to plate divergence is not required to explain (U)HP rock exhumation. The efficiency of the exhumation mechanism depends strongly on the buoyancy and strength of the (U)HP plume, suggesting that in order to exhume rapidly, it must achieve a critical size. By implication, the multiple small Eocene (U)HP complexes within the Internal Crystalline Massifs may have been exhumed as part of a single composite body comprising diverse units aggregated from different levels of the subduction conduit during burial or ascent, rather than as individual small bodies exhumed in separate pulses.

Geochemical data and zircon ages for rocks in a high-pressure belt of Chu-Yili Mountains, southern Kazakhstan: Implications for the earliest stages of accretion in Kazakhstan and the Tianshan

The mechanism and age of Palaeozoic accretion in the Central Asian Orogenic Belt remain poorly constrained. One of the most complex belts extends from the Kokchetav area in northern Kazakhstan to the Kyrgyz northern Tianshan. It represents an assemblage of small blocks with Palaeoproterozoic continental crust, intervening slivers containing early Palaeozoic ophiolites and/or deep-marine sediments, and a number of HP and UHP metamorphic complexes. The HP–LT metamorphic rocks provide important clues for reconstructions of the overall structure and evolution of the accretionary collage. This study is aimed to constrain the metamorphic age and tectonic implications of HP garnet pyroxenites and enclosing mica schists in the Anrakhai area of the Chu-Yili Mountains of southern Kazakhstan. The HP belt is located in the central part of the Anrakhai metamorphic block and extends NW–SE between Neoproterozoic gneisses in the SW and undated ophiolites and granodiorites in the NE. Garnet pyroxenites and their retrograded equivalents form tectonic boudins and blocks in garnet–muscovite and muscovite schist of sedimentary origin. Metamorphic zircons from two garnet pyroxenite samples yielded a SHRIMP mean 206Pb/ 238U age of 489.9 ± 3.1 Ma. This age is interpreted to reflect the time of Early Ordovician peak metamorphism and ongoing subduction in the area as constrained by geological data and suggests that HP metamorphism was related to subduction. Exhumation of the HP rocks occurred between 490 and ∼475 Ma, based on the Early Ordovician age of overlap assemblages. Detrital zircons from a garnet–muscovite schist enclosing the pyroxenites were dated by LA-ICP-MS and range in age from 694 to 2557 Ma. They suggest a maximum late Neoproterozoic age for deposition of the sedimentary protolith and derivation from a continental source including Neoproterozoic to Archaean crustal components. Granodiorites with chemical characteristics of island arc rocks intruded into Proterozoic gneisses in the NE of the HP belt, and magmatic zircons from one sample yielded a SHRIMP 206Pb/ 238U mean age of 508.3 ± 3 Ma. This signifies the existence of a Cambrian magmatic arc. The early Palaeozoic age of the HP garnet pyroxenites indicates that the Anrakhai block is not part of a extensive Precambrian microcontinent, as previously thought, but represents a package of tectonically interlayered slivers, made up of Precambrian basement and early Palaeozoic rocks. Stacking of these heterogeneous domains may be due to subduction of continental crust, mutual underthrusting of continental and ophiolitic rocks, wedge extrusion of HP rocks, and strike-slip deformation in a subduction and/or collision setting. The Anrakhai collision zone is part of larger accretionary belt which formed by the end of the Early Ordovician and may extend from the Kyrgyz northern Tianshan to the Kokchetav area in northern Kazakhstan.

DNA-binding spectra and cleavage studies on Ce(III) complex of 2-[(Trifluoroaceto)aceto]thinophene-piperidine ligands

A kind of complex of CeTTA4 · HP (TTA = 2-[(Trifluoroaceto)aceto]thinophene, HP = piperidine) has been synthesized and characterized, and its DNA-binding properties of CeTTA4 · HP using UV spectra, fluorescent spectra, thermal denaturation, viscometry, molecular modeling and CV (cyclic voltammetry). The results show that the binding-mode between CeTTA4 · HP and DNA is intercalation. The interaction between the complex and DNA has also been investigated by gel electrophoresis. Interestingly, we found that the CeTTA4 · HP complex can cleave circular plasmid pBR322 DNA at pH 7.2 and 37°C. In addition, BDNPP was chosen (bis(2,4-dinitrophenyl)-phosphate) as a model compound to further study its cleavage mechanism for pBR322 DNA. From the first-order kinetics equation, we prove indirectly the mechanism may be hydrolytic cleavage.

The HP1α–CAF1–SetDB1‐containing complex provides H3K9me1 for Suv39‐mediated K9me3 in pericentric heterochromatin

Trimethylation of lysine 9 in histone H3 (H3K9me3) enrichment is a characteristic of pericentric heterochromatin. The hypothesis of a stepwise mechanism to establish and maintain this mark during DNA replication suggests that newly synthesized histone H3 goes through an intermediate methylation state to become a substrate for the histone methyltransferase Suppressor of variegation 39 (Suv39H1/H2). How this intermediate methylation state is achieved and how it is targeted to the correct place at the right time is not yet known. Here, we show that the histone H3K9 methyltransferase SetDB1 associates with the specific heterochromatin protein 1alpha (HP1alpha)-chromatin assembly factor 1 (CAF1) chaperone complex. This complex monomethylates K9 on non-nucleosomal histone H3. Therefore, the heterochromatic HP1alpha-CAF1-SetDB1 complex probably provides H3K9me1 for subsequent trimethylation by Suv39H1/H2 in pericentric regions. The connection of CAF1 with DNA replication, HP1alpha with heterochromatin formation and SetDB1 for H3K9me1 suggests a highly coordinated mechanism to ensure the propagation of H3K9me3 in pericentric heterochromatin during DNA replication.

Interaction of Hydronium Ion with Dibenzo-18-crown-6: NMR, IR, and Theoretical Study

Interaction of dibenzo-18-crown-6 (DBC) with H 3O (+) (HP) in nitrobenzene- d 5 and dichloromethane- d 2 was studied by using (1)H and (13)C NMR spectra and relaxations, FTIR spectra, and quantum chemical DFT calculations. NMR shows that the DBC*HP complex is in a dynamic equilibrium with the reactants, the equilibrium constant K being 0.66 x 10 (3), 1.16 x 10 (4), and 1.03 x 10 (4) L x mol (-1) in CD 2Cl 2, nitrobenzene, and acetonitrile, respectively. The complex appears to have a C 2 v symmetry in NMR, but FTIR combined with DFT normal mode calculations suggest that such high symmetry is only apparent and due to exchange averaging of the structure. FTIR spectra as well as energy-optimized DFT calculations show that the most stable state of the complex in solution is that with three linear hydrogen bonds of HP with one CH 2-O-CH 2 and two Ar-O-Ar oxygen atoms. The structure is similar to that found in solid state but adopts a somewhat different conformation in solution. The dynamics of exchange between bound and free DBC was studied by NMR transverse relaxation. It was found to be too fast to give reproducible results when measured with the ordinary CPMG sequence or its variant DIFTRE removing residual static dipolar interaction, but it could be established by rotating-frame measurements with high intensity of the spin-lock field. The correlation time of exchange was found to be 5.6 x 10 (-6) and 3.8 x 10 (-6) s in dichloromethane and nitrobenzene, respectively. Such fast exchange can be explained by cooperative assistance of present water molecules.

Geology of the Gorny Altai subduction–accretion complex, southern Siberia: Tectonic evolution of an Ediacaran–Cambrian intra-oceanic arc-trench system

The Gorny Altai region in southern Siberia is one of the key areas in reconstructing the tectonic evolution of the western segment of the Central Asian Orogenic Belt (CAOB). This region features various orogenic elements of Late Neoproterozoic–Early Paleozoic age, such as an accretionary complex (AC), high- P/ T metamorphic (HP) rocks, and ophiolite (OP), all formed by ancient subduction–accretion processes. This study investigated the detailed geology of the Upper Neoproterozoic to Lower Paleozoic rocks in a traverse between Gorno-Altaisk city and Lake Teletskoy in the northern part of the region, and in the Kurai to Chagan-Uzun area in the southern part. The tectonic units of the studied areas consist of (1) the Ediacaran (=Vendian)–Early Cambrian AC, (2) ca. 630 Ma HP complex, (3) the Ediacaran–Early Cambrian OP complex, (4) the Cryogenian–Cambrian island arc complex, and (5) the Middle Paleozoic fore-arc sedimentary rocks. The AC consists mostly of paleo-atoll limestone and underlying oceanic island basalt with minor amount of chert and serpentinite. The basaltic lavas show petrochemistry similar to modern oceanic plateau basalt. The 630 Ma HP complex records a maximum peak metamorphism at 660 °C and 2.0 GPa that corresponds to 60 km-deep burial in a subduction zone, and exhumation at ca. 570 Ma. The Cryogenian island arc complex includes boninitic rocks that suggest an incipient stage of arc development. The Upper Neoproterozoic–Lower Paleozoic complexes in the Gorno-Altaisk city to Lake Teletskoy and the Kurai to Chagan-Uzun areas are totally involved in a subhorizontal piled-nappe structure, and overprinted by Late Paleozoic strike-slip faulting. The HP complex occurs as a nappe tectonically sandwiched between the non- to weakly metamorphosed AC and the OP complex. These lithologic assemblages and geologic structure newly documented in the Gorny Altai region are essentially similar to those of the circum-Pacific (Miyashiro-type) orogenic belts, such as the Japan Islands in East Asia and the Cordillera in western North America. The Cryogenian boninite-bearing arc volcanism indicates that the initial stage of arc development occurred in a transient setting from a transform zone to an incipient subduction zone. The less abundant of terrigenous clastics from mature continental crust and thick deep-sea chert in the Ediacaran–Early Cambrian AC may suggest that the southern Gorny Altai region evolved in an intra-oceanic arc-trench setting like the modern Mariana arc, rather than along the continental arc of a major continental margin. Based on geological, petrochemical, and geochronological data, we synthesize the Late Neoproterozoic to Early Paleozoic tectonic history of the Gorny Altai region in the western CAOB.

Theoretical study of the interaction between cytosine and hydrogen peroxide

This work deals with a theoretical study of the interaction between the amino-oxo (a-o) and cis amino-hydroxy (a-h) tautomers of cytosine with one hydrogen peroxide molecule (HP). The optimized geometries, binding energies and harmonic vibrational frequencies are calculated using DFT/B3LYP functional combined with the 6-31++G(d,p) basis set. The results of a NBO analysis are reported as well. Four stable a-o–HP and six stable a-h–HP complexes are found on the potential energy surface. The structures are cyclic, some of them being stabilized by weak intermolecular CH…O interactions. The binding energies range from −12.9 to −47.7 kJ mol −1. HP binds to a-o cytosine 5.4–7.9 kJ mol −1 stronger than to the enol form. The data are compared with uracil–H 2O and uracil–HP complexes. The binding energies corresponding to the formation of C O…HO…HN hydrogen bonds depend exponentially on the proton affinities of the O atoms of the carbonyl and hydroxyl groups and on the deprotonation enthalpies of the OH and NH bonds. The frequencies of the inversion mode of the NH 2 group are very sensitive to the pyramidal character of this group. The ν(CH) stretching vibrations of the CH bonds involved in the interaction show the characteristic features of the blue-shifted hydrogen bonds. The frequency shifts of the ν(OH) vibration of HP and of the ν(CH) vibration of cytosine are discussed in terms of the occupation of the corresponding antibonding orbitals and the rehybridization occurring upon complex formation.

Aluminum chelation by 3-hydroxypyridin-4-ones in the rat demonstrated by microdialysis.

The ability and site of the metal-chelating 3-hydroxypyridin-4-ones (HPs) to mobilize aluminum (Al) was assessed in Al-loaded rats using microdialysis. Four HPs with greatly varying lipophilicity were studied. One week after Al loading, microdialysis probes were implanted in the liver, a jugular vein, and the frontal cortex. An HP was given iv followed by continuous microdialysis for 5 h. Al concentrations in dialysates from the liver increased rapidly and were consistently greater than from blood, suggesting that liver was a primary site of Al chelation. Brain dialysate Al concentrations remained low, suggesting little Al chelation in the brain and little distribution of the Al HP complex into the brain. Al concentrations were determined in the main organs/tissues of a separate group of Al-loaded rats, and the percentage of the total Al body burden in each organ/tissue was calculated. The skeletal system and liver had 57 and 28% of the Al body burden, consistent with the liver as a primary site of Al chelation. The HPs chelate extravascular Al and have been shown by others to be orally active. They warrant further investigation as Al chelators.