Inelastic neutron scattering and Raman spectroscopies and periodic DFT studies of Rb(2)PtH(6) and Rb(2)PtD(6)

The present work has provided a complete set of assignments for the vibrational spectrum of Rb(2)PtH(6) and Rb(2)PtD(6). To confirm the assignments, a periodic density functional theory (DFT) code has been applied to the analysis of the inelastic neutron scattering (INS) spectrum of an ionic material for the first time. The work has also provided an explanation for the unusual infrared spectrum of the potassium salt. The most significant aspect of the work is the use of the momentum transfer information provided by an INS chopper spectrometer. The straightforward method employed for the analysis of the data is applicable to any molecular system (organic or inorganic) and demonstrates the potential of these instruments for chemistry. Periodic DFT was also used to study the other A(2)PtH(6) (A = alkali metal) including, the at present, unknown Li salt, which is found to be stable. The DFT studies have also highlighted the crucial role of the cation in removing charge from the transition metal and "hydride" ligand. It is suggested that this is a general occurrence.     

Dual aperture control on pH- and anion-driven supramolecular nanoscopic hybrid gate-like ensembles

The development of gate-like systems able to perform certain programmed functions is an interesting way of taking chemistry to the frontiers of nanoscience. In relation to this field, we report a complete study of the behavior of a pH-driven and anion-controlled nano-supramolecular gate-like ensemble obtained by anchoring suitable polyamines on the pore outlets of mesoporous materials of the type MCM-41 (solid N3-S). The release of an entrapped dye (Ru(bipy)3(2+)) from the pore voids into the bulk solution allows us to study the gating effect. A pH-driven open/close mechanism was observed that arises from the hydrogen-bonding interaction between amines at neutral pH (open gate) and Coulombic repulsions at acidic pH between closely located polyammoniums at the pore openings (closed gate). Molecular dynamics simulations using force field methods have been carried out to explain the pH-driven open/close mechanism. For this purpose, a mesoporous silica structure was constructed, taking as base the (111) plane of the beta-crystoballite structure on which large hexagonal nanopores and anchored polyamines were included. From these calculations, it was observed how completely unprotonated amines display poor coverage of the pore (fully open gate), whereas completely protonated amines (simulating a pH 2 or lower) result in a clear reduction of the pore aperture, in agreement with the experimental results. In additional to the pH-driven protocol, opening/closing of the gate-like ensemble can also be modulated via an anion-controlled mechanism. This study was carried out by monitoring the dye released from the pore voids of the N3-S solid at a certain pH in the presence of a range of anions with different structural dimensions and charges, including chloride, sulfate, phosphate, and ATP (C(anion) = 1 x 10(-2) mol dm(-3)). The choice of a certain anionic guest results in a different gate-like ensemble behavior, ranging from basically no action (chloride) to complete (ATP) or partial pore blockage, depending on the pH (sulfate and phosphate). The remarkable anion-controllable response of the gate-like ensemble can be explained in terms of anion complex formation with the tethered polyamines. These experimental studies are also in agreement with computational simulations with fluoride, chloride, iodide, and dihydrogen phosphate anions. In the model, larger anions push the tethered polyamines toward the pore openings more efficiently, and therefore the pore aperture decreases. The studies also show that, for anions showing a strong tendency to form hydrogen-bonding networks (e.g., phosphate), complete pore blockage was observed at acidic pH. Finally, selectivity patterns have been discussed in terms of kinetic rates of the liberation of the Ru(bipy)3(2+) dye from the amine-functionalized dye-containing material N3-S.     

Solid-phase extraction and determination of dansyl derivatives of unconjugated and acetylated polyamines by reversed-phase liquid chromatography: improved separation systems for polyamines in cerebrospinal fluid, urine and tissue

A sensitive and simple liquid chromatographic assay with fluorometric detection for unconjugated and acetylated polyamines in biological fluids is described. After precolumn derivatization with dansyl chloride, unconjugated polyamines and acetylated polyamines were extracted by elution from a Bond-Elut C18 column and then separated on a reversed-phase column with gradient elution. The complete analysis of unconjugated putrescine, spermidine, and spermine in either hydrolyzed urine, cerebrospinal fluid or tissue could be accomplished within 20-26 min, while the simultaneous analysis of unconjugated polyamines and monoacetylpolyamines could be completed within 40 min. Unhydrolyzed urine and cerebrospinal fluid required a Bond-Elut cation-exchange clean-up before dansylation. Standard curves for the assay were linear up to 20 nmol/ml, and the within-day and day-to-day coefficients of variation were between 1.1 and 4.6% and between 1.6 and 11.8%, respectively. Results obtained with the method were compared with results obtained with a well established modified amino acid analyzer method for urine, tissue and cerebrospinal fluid samples. The correlation coefficients between these two methods were in the range 0.933-0.996. Detection limits between 50 and 150 fmol were achieved for unconjugated and acetylated polyamines. Of more than twenty drugs and amines tested for possible interference with the assay, only normetanephrine was found to have the same retention time as the internal standard 1,6-diaminohexane.     

Determination of polyamines in urine of normal human and cancer patients by capillary gas chromatography

A capillary gas chromatographic method is described for the determination of polyamines (putrescine, spermidine and spermine) in the urine of normal human and cancer patients. Morning urine after acid hydrolysis is cleaned up on a silica gel column and derivatized with trifluoroacetic-anhydride. Creatinine in human urine is used as internal standard. Recoveries of polyamines are 96.7% putrescine, 102.6% spermidine (Spd), and 98.7% spermine. SD of the method for Spd is 1.949 +/- 0.041 (micrograms/mg creatinine, mean +/- SD, n = 5). The results show that the mean level of polyamines in cancer patients urine is much higher than that in normal human urine. The mean of total polyamines in the normal human and the cancer patients is 2.01 and 44.74, respectively (g/mg creatinine).     

In Situ Reprogramming of Tumor-Associated Macrophages with Internally and Externally Engineered Exosomes

The reprogramming of tumor-associated macrophages (TAMs) has emerged as an efficient strategy for immunotherapy. However, most of the approaches did not allow the in situ reprogramming of TAM because their low efficiency, non-specificity, or potential side effects. Herein, we produced exosomes with the clustered regularly interspaced short palindromic repeats interference (CRISPRi) internally engineered and the TAM specific peptide externally engineered onto the exosome membrane. The i nternally and e xternally e ngineered e xosomes ( IEEE , also named as I3E ) allowed the selective homing to tumor tissue and targeted to M2-like TAMs, which nearly repressed the expression of PI-3 kinase gamma (PI3Kγ) completely, and induced the TAMs polarizing to M1 both in vitro and in vivo. The polarized M1 macrophages awakened the “hot” tumor-immunity, causing the increase of T lymphocyte infiltration and the decrease of myeloid-derived suppressor cells, and inhibiting the tumor growth significantly. I3E reprogramed TAMs in situ precisely and efficiently.     

Thermodynamic parameters for the binding of polycarboxylic anions by fully methyl substituted linear polyammonium cations

Enthalpy changes for the binding of malonate, citrate, 1,2,3-propanetricarboxylate and 1,2,3,4-butanetetracarboxylate by fully methyl substituted linear polyammonium cations (with the general formula C3nNnH(8n + 2)n+, with n = 1,2,3) were determined calorimetrically. Enthalpy changes were also determined for the binding of malonate by unsubstituted polyammonium cations (with the general formula C2(n - 1)NnH(6n - 2)n+, n = 1...6). delta H0/kJ mol-1 values are always positive and strongly dependent on the charges involved in the formation reaction. Mean values for delta G0 and T delta S0 were obtained as a function of the charge product zeta = Zanion/ Zcation: -delta G0/kJmol-1 = (4.0 +/- 0.4) zeta, T delta S0/kJmol-1 = (5.9 +/- 0.1) zeta (substituted polyamines), and -delta G0/kJmol-1 = (3.5 +/- 0.2) zeta, T delta S0/kJmol-1 = (5.0 +/- 0.4) zeta (unsubstituted polyamines). For both classes of amines it was found that T delta S0 vs. delta G0 is linear with a correlation coefficient of r = 0.9618. Crude approximation gives -delta G0/kJmol-1 = (7.0 +/- 0.4) n-1, T delta S0/kJmol-1 = (10.0 +/- 0.8) n-1 for unsubstituted amines and -delta G0/kJmol-1 = (8.0 +/- 0.8) n-1, T delta S0/kJmol-1 = (11.8 +/- 2.0) n-1 (n = number of possible salt bridges, or single interactions) for substituted amines.     

Mass fragmentographic identification of polyamine metabolites in the urine of normal persons and cancer patients, and its relevance to the use of polyamines as tumour markers

The mass fragmentographic identification of N-(2-carboxyethyl)-4-amino-n-butyric acid, N-(3-aminopropyl)-N1-(2-carboxyethyl)-1,4-diaminobutane, N,N1-bis(2-carboxyethyl)-1,4-diaminobutane, and delta-aminovaleric acid in acid-hydrolysed urines of a normal person and two cancer patients is described. A previous study, in which the metabolic fate of intraperitoneally injected polyamines in rats was investigated, revealed that these compounds should be considered as non-alpha-amino acid metabolites of the naturally occurring polyamines. Quantification of polyamines and their non-alpha-amino acid metabolites by gas chromatography with nitrogen--phosphorus detection showed that, relative to the parent polyamines, humans normally excrete higher quantities of polyamine catabolites in urine than rats, suggesting that humans catabolize polyamines more efficiently. As illustrated by the follow-up of the concentrations of polyamines and their catabolites in the urine of a patient with high-grade non-Hodgkin lymphoma during chemotherapy, the catabolic pressure on polyamines may be considerably increased during neoplastic diseases, since an even higher proportion of oxidized polyamine metabolites was observed. It is therefore suggested that the additional measurement of the circulating concentrations of polyamine-degrading enzymes is of importance for the correct interpretation of polyamine (metabolite) determinations for oncological purposes.     

Thermodynamic parameters for the binding of inorganic and organic anions by biogenic polyammonium cations

Thermodynamic parameters for the interaction of protonated biogenic polyamines with inorganic or organic polyanions were studied potentiometrically (H(+)-glass electrode) and calorimetrically, at 25 degrees C. No background salt was used in the measurements to avoid interferences, and the formation constants and formation enthalpies were extrapolated to zero ionic strength. Species formed are ALH(r) [L=Cl(-), SO(4)(2-), HPO(4)(2-), P(2)O(7)(4-) and P(3)O(10)(5-); tartrate, malate, citrate, glutamate, 1,2,3-propanetricarboxylate, 1,2,3,4-butanetetracarboxylate], with r=1,2...(n+m-2) and r=1,2...(n+m-1) for inorganic and organic ligands, respectively (n, m=maximum degree of protonation of amine and ligand, respectively). The stability of the various species formed is a function of charges involved in the formation reaction. DeltaH(0) values are generally positive, and therefore these complexes are entropically stabilized. Results are discussed in connection with several previously reported data on similar systems. DeltaG(0) and TDeltaS(0) follow a linear trend as a function of polyammonium cation and inorganic or carboxylic anion charges. DeltaG(0) and TDeltaS(0) charge relationships are reported. In particular, mean values of DeltaG(0) and TDeltaS(0) for single interaction were calculated: DeltaG(0)=7.0 kJ mol(-1) n(-1), TDeltaS(0)=9.1 kJ mol(-1) n(-1) and DeltaG(0)=5.7 kJ mol(-1) n(-1) and TDeltaS(0)=8.7 kJ mol(-1) n(-1), for the species of inorganic and organic polyanions, respectively (n=number of possible salt bridges). A linear relationship was also found for TDeltaS(0) versus DeltaG(0), whose equation is TDeltaS(0)=-7-1.39 DeltaG(0) (with r=0.9409; r, correlation coefficient). The body of correlations found for these thermodynamic parameters shows quite good predictive value.     

Nonorthogonal Tight-binding Study of the Geometries and Electronic Properties of Ge_n(n=2—20)Clusters

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Electronic and molecular structure of high-spin d4 complexes: experimental and theoretical study of the [Cr(D2O)6]2+ cation in Tutton's salts

Variable-temperature spectroscopic and crystallographic studies on the chromium(II) Tutton's salts, (MI)2Cr(X2O)6(SO4)2, where MI = ND4+, Rb+, or Cs+, and X = H or D, are reported. Inelastic neutron scattering (INS) and multifrequency EPR experiments facilitate a rigorous definition of the ground-state electronic structure from 1.5 up to 296 K, which is unprecedented for a high-spin d4 complex. Modeling of the INS data using a conventional S = 2 spin Hamiltonian reveals a dramatic variation in the axial and rhombic zero-field-splitting parameters. For the ammonium salt, D and E are -2.454(3) and 0.087(3) cm(-1) at 10 K and -2.29(2) and 0.16(3) cm(-1) at 250 K, respectively. A temperature variation in the stereochemistry of the [Cr(D2O)6]2+ complex is also identified, with an apparent coalescence of the long and medium Cr-O bond lengths at temperatures above 150 K. The corresponding changes for the rubidium and cesium salts are notable, though less pronounced. The experimental quantities are interpreted using a 5Ee Jahn-Teller Hamiltonian, perturbed by anisotropic strain. It is shown that good agreement can be obtained only by employing a model in which the anisotropic strain is itself temperature dependent. A new theoretical approach for calculating variable-temperature EPR spectra of high-spin d4 complexes, developed within the 5Ee coupling model, is described. Differences between spin-Hamiltonian parameters determined by INS and EPR are consistent with those of the different time scales of the two techniques.     

The structure of protonated diamines and polyamines

The reduced mobilities in air, at 200C, of six isomeric C₇H₁₈N₂ protonated diamines, two triamines (caldine and spermidine), and two tetramines (thermine and spermine) were measured by ion mobility spectrometric (IMS) techniques. The results indicated that all these polyamines undergo proton-induced cyclization, with the proton forming a bridge between two amino groups. It appears as if the favored configuration of the protonated polyamines involves a six- or seven-membered ring rather than a bridge between the terminal amino groups. It is believed that in the tetramines the cyclic structure is formed between the two central, more basic, secondary amine sites.     

A combined experimental inelastic neutron scattering, Raman and ab initio lattice dynamics study of α-lithium amidoborane

A combination of inelastic neutron scattering (INS) spectroscopy and Raman spectroscopy with periodic density functional theory calculations is used to provide a complete assignment of the vibrational spectra of α-lithium amidoborane (α-LiNH(2)BH(3)). The Born charge density and the atomic motion up to the decomposition temperature have been modelled. These models not only explain the nature of bonding in α-LiNH(2)BH(3) but also provide an insight into the atomic mechanisms of its decomposition. The (INS) measurements were performed in the range of 0-4000 cm(-1) on the high-resolution time-of-flight TOSCA INS spectrometer at the ISIS Spallation Neutron Source at the Rutherford Appleton Laboratory.     

螯合树脂研究——Ⅴ.巯基胺型螯合树脂的合成其吸附性能

本工作探索了一种合成巯基胺型螯合树脂的新方法.用环硫氯丙烷与多乙烯多胺作用只经一步反应,即可制得交联型巯基胺树脂,树脂中的配位原子氮和硫的含量较高,对贵金属离子金、银、钯具有良好的吸附性能.     

Application of pharmacia automated FPLC System and PepRPC HR 5/5 bonded phase column for determination of dansylated polyamines

Summary The Pharmacia Automatized FPLC System equipped with a PepRPC HR 5/5 bonded-phase column was tested with dansyl polyamines, toluene, dimethyl- and dibutylphthalate, using either isocratic conditions or linear gradient-elution program of methanol in water as the mobile phase. A simple and reproducible method is described for the quantiation of dansylated natural polyamines, such as putrescine, spermidine and spermine originating from P388/S leukemia cells. Comparing the data from analyses performed in parallel by the Automated FPLC/PepRPC HR 5/5, and a Hewlett-Packard Model 1084B/LiChrosorb RP-8 systems a linear correlation has been found, with a regression coefficient of r=0.974.     

Chirality-Dependent Reprogramming of Macrophages by Chiral Nanozymes

It is known that extracellular free radical reactive oxygen species (ROS) rather than intracellular ROS plays a non-substitutable role in regulation of tumor-suppressing (M1) tumor-associated macrophages (TAMs) polarization. However, most therapeutic nanoplatforms mainly provide intracellular ROS and exhibit insufficient accumulation near TAMs, which strongly limits the macrophage-based immunotherapeutic effects. Here we design and synthesize chiral MoS₂/CoS₂ nanozymes with peroxidase (POD)-like and catalase (CAT)-like activities to efficiently modulate TAMs polarization and reverse tumor immunosuppression by harnessing their chirality-specific interactions with biological systems. MoS₂/CoS₂ nanoparticles coordinated with d -chirality (d -NPs, right-handed) show improved pharmacokinetics with longer circulating half-life and higher tumor accumulation compared with their l ( left-handed)- and dl ( racemate)-counterparts. Further, d -NPs can escape from macrophage uptake in the tumor microenvironment (TME) with the aid of cell-unpreferred opposite chirality and act as extracellular hydroxyl radicals (⋅OH) and oxygen (O₂) generators to efficiently repolarize TAMs into M1 phenotype. On the contrary, l -NPs showed high cellular uptake due to chirality-driven homologous adhesion between l -NPs and macrophage membrane, leading to limited M1 polarization performance. As the first example for developing chiral nanozymes as extracellular-localized ROS generators to reprogram TAMs for cancer immunotherapy, this study opens an avenue for applications of chiral nanozymes in immunomodulation.     

Competing interactions in the tetranuclear spin cluster [Ni[(OH)(2)Cr(bispictn)](3)]I(5).5H(2)O. An inelastic neutron scattering and magnetic study

The properties of the spin state manifold of the tetranuclear cluster Ni[(OH)(2)Cr(bispictn)](3)]I(5).5H(2)O (bispictn = N,N'-bis(2-pyridylmethyl)-1,3-propanediamine) are investigated by combining magnetic susceptibility and magnetization measurements with an inelastic neutron scattering (INS) study on an undeuterated sample of Ni[(OH)(2)Cr(bispictn)](3)]I(5).5H(2)O. The temperature dependence of the magnetic susceptibility indicates an S = (1)/(2) ground state, which requires antiferromagnetic interactions both between Cr(3+) and Ni(2+) ions and among the Cr(3+) ions. INS reveals potential single-ion anisotropies to be negligibly small and enables an accurate determination of the exchange parameters. The best fit to the experimental energy level diagram is obtained by an isotropic spin Hamiltonian H = J(CrNi)(S(1)().S(4)() + S(2)().S(4)() + S(3)().S(4)()) + J(CrCr)(S(1)().S(2)() + S(1)().S(3)() + S(2)().S(3)()) with J(CrNi) = 1.47 cm(-)(1) and J(CrCr) = 1.25 cm(-)(1). With this model, the experimental intensities of the observed INS transitions as well as the temperature dependence of the magnetic data are reproduced. The resulting overall antiferromagnetic exchange is rationalized in terms of orbital exchange pathways and compared to the situation in oxalato-bridged clusters.     

Polyamines Upregulate Cephalosporin C Production and Expression of β-Lactam Biosynthetic Genes in High-Yielding Acremonium chrysogenum Strain

The high-yielding production of pharmaceutically significant secondary metabolites in filamentous fungi is obtained by random mutagenesis; such changes may be associated with shifts in the metabolism of polyamines. We have previously shown that, in the Acremonium chrysogenum cephalosporin C high-yielding strain (HY), the content of endogenous polyamines increased by four- to five-fold. Other studies have shown that the addition of exogenous polyamines can increase the production of target secondary metabolites in highly active fungal producers, in particular, increase the biosynthesis of β-lactams in the Penicillium chrysogenum Wis 54–1255 strain, an improved producer of penicillin G. In the current study, we demonstrate that the introduction of exogenous polyamines, such as spermidine or 1,3-diaminopropane, to A. chrysogenum wild-type (WT) and HY strains, leads to an increase in colony germination and morphological changes in a complete agar medium. The addition of 5 mM polyamines during fermentation increases the production of cephalosporin C in the A. chrysogenum HY strain by 15–20% and upregulates genes belonging to the beta-lactam biosynthetic cluster. The data obtained indicate the intersection of the metabolisms of polyamines and beta-lactams in A. chrysogenum and are important for the construction of improved producers of secondary metabolites in filamentous fungi.     

Spectroscopic, magnetochemical, and crystallographic study of cesium iron phosphate hexahydrate: characterization of the electronic structure of the iron(II) hexa-aqua cation in a quasicubic environment

Spectroscopic, magnetochemical, and crystallographic data are presented for CsFe(H2O)6PO4, a member of a little-known isomorphous series of salts that facilitates the study of hexa-aqua ions in a quasicubic environment. Above 120 K, the deviations from cubic symmetry are minimal, as shown by the first example of an iron(II) M?ssbauer spectrum that exhibits no measurable quadrupole splitting. Two crystallographically distinct [Fe(OH2)6]2+ complexes are identified from inelastic neutron-scattering (INS) experiments conducted between 2 and 15 K. The data are modeled with the ligand-field Hamiltonian, H = lambdaL? + betaB(kL + 2?) + Delta(tet){Lz2 - (1/3)L(L + 1)} + Delta(rhom){Lx2 - Ly2}, operating in the ground-term (5)T(2g) (Oh) basis. An excellent reproduction of INS, M?ssbauer, HF-EPR, and magnetochemical data are obtained in the 2 and 15 K temperature regimes with the following parameters: lambda = -80 cm(-1); k = 0.8; site A Delta(tet) = 183 cm(-1), Delta(rhom)= 19 cm(-1); site B Delta(tet) = 181 cm(-1), Delta(rhom)= 12 cm(-1). The corresponding zero-field-splitting (ZFS) parameters of the conventional S = 2 spin Hamiltonian are as follows: site A D = 12.02 cm(-)(1), E = 2.123 cm(-1); site B D = 12.15 cm(-1), E = 1.37 cm(-1). A theoretical analysis of the variation of the energies of the low-lying states with respect to displacements along selected normal coordinates of the [Fe(OH2)6]2+, shows the zero-field splitting to be extremely sensitive to small structural perturbations of the complex. The expressions derived are discussed in the context of spin-Hamiltonian parameters reported for the [Fe(OH2)6]2+ cation in different crystalline environments.     

Chromatographic behavior of open-chain polyamines NH2-(CH2)2-[NH-(CH2)2]n-NH2 and their quantitative determination in sea water by high-performance ion-exchange chromatography

The results are reported of a study using high-performance liquid chromatography for the chromatographic behavior of a homologous series of open-chain polyamines having the general molecular formula NH2-(CH2)2-[NH-(CH2)2]n-NH2 (n = 0-4). The exchange column is a carboxylate-functionalized resin. Amines are eluted with mixtures of HClO4 0.200 mol/L, NaClO4 from 0.100 to 1.40 mol/L, and acetonitrile (ACN) from 0% to 40% (v/v) and detected amperometrically. The dependence of the retention factor k' on sodium and ACN concentrations in the eluent and the total number of nitrogen atoms in the amines are considered and discussed. Suitable relationships are derived. Examples of polyamines separation are given, and a quantitative determination of analytes in spiked sea water is shown.