Differential contribution of HLA-DR,DQ, and TAP2 alleles to systemic lupus erythematosus susceptibility in Spanish patients: role of TAP2*01 alleles in Ro autoantibody production

OBJECTIVE—To study the influence MHC class II and TAP2 alleles exert on systemic lupus erythematosus (SLE) susceptibility and on the clinical and serological manifestations of the disease, in a cohort of Spanish patients.
METHODS—HLA-DR serological typing and HLA-DQA, DQB, and TAP2 DNA sequence specific oligotyping, were carried out in 85 unrelated Spanish SLE patients and 186 healthy controls. Autoantibodies detection was carried out by indirect immunofluorescence and counter immunoelectrophoresis.
RESULTS—Total SLE group: the frequency of HLA-DR3 and HLA-DQA1*0501 is significantly increased in this group (p_c<0.005, δ=0.34 and p_c<0.005, δ= 0.45, respectively) although the highest δ value (δ=0.87) is obtained when the TAP2*01 alleles are considered. No DQB allele shows significant deviation from the control group. Renal damage: it mainly occurs in HLA-DR3 patients (p_c<0.0005 and δ=0.72). HLA-DQA1*0501 (p_c<0.05, δ=0.57) and DQB1*0201 (p_c NS, δ=0.56) are weaker susceptibility factors. Ro+ (but not La) group: this autoantibody response is associated with TAP2*01 alleles in homozygosity (p<0.05, δ=0.81). Ro/La+ group: it has a different genetic background as HLA-DQA1*0501 (δ=1) and HLA-DQB1*0201 (δ=1) are the main susceptibility factors.
CONCLUSIONS—A differential association between HLA-DR, DQA1, and DQB1 alleles and SLE or its clinical and serological manifestations are found. Furthermore, the associations are different to the ones reported in other ethnic groups. Finally, TAP2*01 group of alleles are associated with the highest susceptibility to SLE (higher than HLA-DR3) and may influence Ro (but not La) autoantibodies production, whereas HLA-DQA1*0501 and DQB1*0201 mediates concomitant Ro and La production.

     

Synthesis,Crystal Structure and Luminescent Property of Mg(II) Complex with N-Benzenesulphonyl-L-Leucine and 1,10-Phenanthroline

A new complex [Mg(L)₂(phen)(H₂O)₂](phen)(H₂O)₂ [L= N-benzenesulphonyl-L-leucine] was synthesized by the reaction of magnesium chloride hexahydrate with N-benzenesulphonyl-L-leucine and 1,10-phenanthroline in the CH₃CH₂OH/H₂O (v:v = 5:1). It was characterized by elemental analysis, IR and X-ray single crystal diffraction analysis. The crystal of the title complex [Mg(L)₂(phen)(H₂O)₂](phen)(H₂O)₂ belongs to triclinic, space group P-1 with a = 0.72772(15) nm, b = 1.4279(3) nm, c = 1.4418(3) nm, α = 63.53(3)°, β = 79.75(3)°, γ = 81.83(3)°, V = 1.3163(5) nm³, Z =1, D_c= 1.258 μg·m⁻³, μ = 0.177 mm⁻¹, F(000) = 526, and final R₁ = 0.0506, ωR₂ = 0.1328. The complex comprises a six-coordinated magnesium(II) center, with a N₂O₄ distorted octahedron coordination environment. The molecules are connected by hydrogen bonds and π-π stacking to form one dimensional chain structure. The luminescent property of the Mg(II) complex has been investigated in solid.     

A relation between automorphic forms on GL(2) and GL(3)

Let ρ_n denote the standard n-dimensional representation of GL(n,C) and ρ_n² its symmetric square. For each automorphic cuspidal representation π of GL(2,A) we introduce an Euler product L(s,π,ρ₂²) of degree 3 which we prove is entire. We also prove that there exists an automorphic representation II of GL(3)—“the lift of π”—with the property that L(s,II,ρ₃) = L(s,π,ρ₂²). Our results confirm conjectures described in a more general context by R. P. Langlands [(1970) Lecture Notes in Mathematics, no. 170 (Springer-Verlag, Berlin-Heidelberg-New York)].     

Interaction between the intermediary electron acceptor (pheophytin) and a possible plastoquinone-iron complex in photosystem II reaction centers

Photoreduction of the intermediary electron acceptor, pheophytin (Pheo), in photosystem II reaction centers of spinach chloroplasts or subchloroplast particles (TSF-II and TSF-IIa) at 220 K and redox potential E_h = -450 mV produces an EPR doublet centered at g = 2.00 with a splitting of 52 G at 7 K in addition to a narrow signal attributed to Pheo^[unk] (g = 2.0033, ΔH ≈ 13 G). The doublet is eliminated after extraction of lyophilized TSF-II with hexane containing 0.13-0.16% methanol but is restored by reconstitution with plastoquinone A (alone or with β-carotene) although not with vitamin K₁. TSF-II and TSF-IIa are found to contain ≈2 nonheme Fe atoms per reaction center. Incubation with 0.55 M LiClO₄ plus 2.5 mM o-phenanthroline (but not with 0.55 M LiClO₄ alone) decreases this value to ≈0.6 and completely eliminates the EPR doublet, but photoreduction of Pheo is not significantly affected. Partial restoration of the doublet (about 25%) was achieved by subsequent incubation with 0.2 mM Fe²⁺, but not with either Mn²⁺ or Mg²⁺. The Fe removal results in the development of a photoinduced EPR signal (g = 2.0044 ± 0.0003, ΔH = 9.2 ± 0.5 G) at E_h = 50 mV, which is not observed after extraction with 0.16% methanol in hexane. It is ascribed to plastosemiquinone no longer coupled to Fe in photosystem II reaction centers. The results show that a complex of plastoquinone and Fe can act as the stable “primary” electron acceptor in photosystem II reaction centers and that the interaction of its singly reduced form with the reduced intermediary acceptor, Pheo^[unk], is responsible for the EPR doublet.     

Conformation of cyclo(-L-Pro-Gly-)(3) and its Ca and Mg complexes

The synthetic hexapeptide cyclo(-L-Pro-Gly-)₃ is an ionophore that shows interesting conformational changes upon binding metal ions. X-ray crystallographic studies of this peptide show that when it is crystallized from an ethanol/ethyl acetate mixture the ring takes up an asymmetric conformation containing one cis peptide bond. In crystals of a Ca²⁺ complex, the cation is sandwiched between two peptide molecules that differ markedly in conformation. However, both exhibit threefold symmetric forms, with all six peptide bonds in the molecule occurring in the usual trans conformation. The Ca²⁺ is octahedrally surrounded by six glycyl carbonyl oxygens from the two peptides at an average distance of 2.26 Å and can easily be released by the disruption of the peptide sandwich. In the magnesium complex, the peptide forms a 1:1 complex with the ion. The Mg²⁺ is octahedrally coordinated to three glycyl carbonyls and three water oxygens. The average coordination distance between magnesium and the peptide oxygens is 2.03 Å and that between magnesium and water oxygen is 2.11 Å. The two peptide molecules in the asymmetric unit have similar conformations and have approximate threefold symmetry.     

An attempt to distinguish between the actions of neuromuscular blocking drugs on the acetylcholine receptor and on its associated ionic channel

The effects of lobeline and tubocurarine on the voltage-clamped endplates of frog sartorius and cutaneous pectoris muscles were examined at room temperature (20-23°C). Like tubocurarine, lobeline causes nondepolarizing neuromuscular blockade. The half-time of decay (t_½) of endplate currents (e.p.c.s) recorded at a holding potential (V_m) of -90 mV was significantly shorter in endplates treated with lobeline (50 μM; mean t_½ ± SEM = 0.41 ± 0.02 ms) or tubocurarine (11.4 μM; t_½ = 0.64 ± 0.04 ms) than in those treated with Mg²⁺ (13 mM; t_½ = 1.39 ± 0.11 ms) or a low concentration of tubocurarine (3 μM; t_½ = 0.87 ± 0.05 ms). Similarly, lobeline (10 μM) shortened the t_½ of untreated miniature e.p.c.s by 35%; tubocurarine, however, abolished miniature e.p.c.s at the concentration required to observe its actions on e.p.c. decay kinetics. The t_½ of e.p.c.s recorded from preparations treated with Mg²⁺ (13 mM), tubocurarine at low concentrations (3 μM), or untreated miniature e.p.c.s was logarithmically related to V_m, being slower at more hyperpolarized values. By contrast, the t_½s of e.p.c.s recorded in either lobeline (50 μM) or tubocurarine (11.4 μM) were independent of voltage in the range -150 to -80 mV. The ability of lobeline to shorten t_½ and to remove the voltage dependence of t_½ was partially antagonized by Mg²⁺ (13 mM). As expected, when lobeline or tubocurarine was removed from the bath or when acetylcholine release from the motor nerve terminals was increased by 4-aminopyridine (20 μM) and Ca²⁺ (10 mM) (in the presence of lobeline or tubocurarine), the amplitude of e.p.c.s increased as a function of time. However, the t_½ of the decay phase of the e.p.c.s remained shortened (i.e., unaltered from the earlier treatment). These results suggest that both tubocurarine and lobeline have at least two distinct postjunctional actions including: (i) a block of the acetylcholine receptor and (ii) a block of the ionic channel associated with the acetylcholine receptor.     

Synthesis,Crystal Structure and Luminescent Property of Cd (II) Complex with N-Benzenesulphonyl-L-leucine

A new trinuclear Cd (II) complex [Cd₃(L)₆(2,2-bipyridine)₃] [L = N-phenylsulfonyl-L-leucinato] has been synthesized and characterized by elemental analysis, IR and X-ray single crystal diffraction analysis. The results show that the complex belongs to the orthorhombic, space group P2₁2₁2₁ with a = 16.877(3) Å, b = 22.875(5) Å, c = 29.495(6) Å, α = β = γ = 90°, V = 11387(4) ų, Z = 4, D_c= 1.416 μg·m⁻³, μ = 0.737 mm⁻¹, F (000) = 4992, and final R₁ = 0.0390, ωR₂ = 0.0989. The complex comprises two seven-coordinated Cd (II) atoms, with a N₂O₅ distorted pengonal bipyramidal coordination environment and a six-coordinated Cd (II) atom, with a N₂O₄ distorted octahedral coordination environment. The molecules form one dimensional chain structure by the interaction of bridged carboxylato groups, hydrogen bonds and π-π interaction of 2,2-bipyridine. The luminescent properties of the Cd (II) complex and N-Benzenesulphonyl-L-leucine in solid and in CH₃OH solution also have been investigated.     

Organometallic mechanism of action and inhibition of the 4Fe-4S isoprenoid biosynthesis protein GcpE (IspG)

We report the results of a series of chemical, EPR, ENDOR, and HYSCORE spectroscopic investigations of the mechanism of action (and inhibition) of GcpE, E-1-hydroxy-2-methyl-but-2-enyl-4-diphosphate (HMBPP) synthase, also known as IspG, an Fe₄S₄ cluster-containing protein. We find that the epoxide of HMBPP when reduced by GcpE generates the same transient EPR species as observed on addition of the substrate, 2-C-methyl-D-erythritol-2, 4-cyclo-diphosphate. ENDOR and HYSCORE spectra of these transient species (using ²H, ¹³C and ¹⁷O labeled samples) indicate formation of an Fe-C-H containing organometallic intermediate, most likely a ferraoxetane. This is then rapidly reduced to a ferracyclopropane in which the HMBPP product forms an η²-alkenyl π- (or π/σ) complex with the 4th Fe in the Fe₄S₄ cluster, and a similar “metallacycle” also forms between isopentenyl diphosphate (IPP) and GcpE. Based on this metallacycle concept, we show that an alkyne (propargyl) diphosphate is a good (K_i ∼ 300 nM) GcpE inhibitor, and supported again by EPR and ENDOR results (a ¹³C hyperfine coupling of ∼7 MHz), as well as literature precedent, we propose that the alkyne forms another π/σ metallacycle, an η²-alkynyl, or ferracyclopropene. Overall, the results are of broad general interest because they provide new mechanistic insights into GcpE catalysis and inhibition, with organometallic bond formation playing, in both cases, a key role.     

High Mechanic Enhancement of Chopped Carbon Fiber Reinforced-Low-Density Unsaturated Polyester Resin Composite at Low Preparation Temperature with Facile Polymerization

Chopped carbon fiber-reinforced low-density unsaturated polyester resin (CCFR-LDUPR) composite materials with light weight and high mechanical properties were prepared at low temperature and under the synergistic action of methyl ethyl ketone peroxide (MEKP-II) and cobalt naphthenate. Optimal preparation conditions were obtained through an orthogonal experiment, which were preparation temperature at 58.0 °C, 2.00 parts per hundred of resin (phr) of NH₄HCO₃, 4.00 phr of chopped carbon fibers (CCFs) in a length of 6.0 mm, 1.25 phr of initiator and 0.08 phr of cobalt naphthenate. CCFR-LDUPR composite sample presented its optimal properties for which the density (ρ) was 0.58 ± 0.02 g·cm⁻³ and the specific compressive strength (P_s) was 53.56 ± 0.83 MPa·g⁻¹·cm³, which is 38.9% higher than that of chopped glass fiber-reinforced low-density unsaturated polyester resin (CGFR-LDUPR) composite materials. Synergistic effects of initiator and accelerator accelerated the specific polymerization of resin in facile preparation at low temperature. Unique “dimples”, “plate microstructure” and “surface defect” fabricated the specific microstructure of the matrix of CCFR-LDUPR composite samples, which was different from that of cured unsaturated polyester resin (UPR) with “body defect” or that of CGFR-LDUPR with coexistence of “surface defect” and “body defect”.     

Picosecond photochemistry of a cofacial diporphyrin containing iron(III) and zinc(II): Mimicking electron transfer between cytochrome c and the primary electron donor in reaction centers of photosynthetic bacteria

Comparison of picosecond kinetic and spectroscopic data for Zn octaethylporphine and Fe(III)Cl octaethylporphine with that for Zn—Fe(III)Cl, a cofacial diporphyrin composed of a Zn porphyrin covalently bound to an Fe(III)Cl porphyrin with two chains of five atoms each, supports the assignment of a light-driven electron transfer (k > 10¹¹s^-1) within Zn—Fe(III)Cl to form [Zn⁺·—Fe(II)]Cl. The kinetics (k ≈ 10¹⁰s^-1) and thermodynamics of the reverse electron transfer are compared to those of a similar electron transfer in bacterial photosynthesis, the reduction of an oxidized bacteriochlorophyll dimer, (BChl)₂⁺·, by Fe(II) cytochrome c.     

Synthesis and biological evaluation of fluorinated deoxynucleotide analogs based on bis-(difluoromethylene)triphosphoric acid

It is difficult to overestimate the importance of nucleoside triphosphates in cellular chemistry: They are the building blocks for DNA and RNA and important sources of energy. Modifications of biologically important organic molecules with fluorine are of great interest to chemists and biologists because the size and electronegativity of the fluorine atom can be used to make defined structural alterations to biologically important molecules. Although the concept of nonhydrolyzable nucleotides has been around for some time, the progress in the area of modified triphosphates was limited by the lack of synthetic methods allowing to access bisCF₂-substituted nucleotide analogs—one of the most interesting classes of nonhydrolyzable nucleotides. These compounds have “correct” polarity and the smallest possible steric perturbation compared to natural nucleotides. No other known nucleotides have these advantages, making bisCF₂-substituted analogs unique. Herein, we report a concise route for the preparation of hitherto unknown highly acidic and polybasic bis(difluoromethylene)triphosphoric acid 1 using a phosphorous(III)/phosphorous(V) interconversion approach. The analog 1 compared to triphosphoric acid is enzymatically nonhydrolyzable due to substitution of two bridging oxygen atoms with CF₂ groups, maintaining minimal perturbations in steric bulkiness and overall polarity of the triphosphate polyanion. The fluorinated triphosphoric acid 1 was used for the preparation of the corresponding fluorinated deoxynucleotides (dNTPs). One of these dNTP analogs (dT) was demonstrated to fit into DNA polymerase beta (DNA pol β) binding pocket by obtaining a 2.5 Å resolution crystal structure of a ternary complex with the enzyme. Unexpected dominating effect of triphosphate/Mg²⁺ interaction over Watson–Crick hydrogen bonding was found and discussed.     

A First-Principles Study of the Cu-Containing β″ Precipitates in Al-Mg-Si-Cu Alloy

The nanostructured β″ precipitates are critical for the strength of Al-Mg-Si-(Cu) aluminum alloys. However, there are still controversial reports about the composition of Cu-containing β″ phases. In this work, first-principles calculations based on density functional theory were used to investigate the composition, mechanical properties, and electronic structure of Cu-containing β″ phases. The results predict that the Cu-containing β″ precipitates with a stoichiometry of Mg_4+xAl_2−xCuSi₄ (x = 0, 1) are energetically favorable. As the concentration of Cu atoms increases, Cu-containing β″ phases with different compositions will appear, such as Mg₄AlCu₂Si₄ and Mg₄Cu₃Si₄. The replacement order of Cu atoms in β″ phases can be summarized as one Si3/Al site → two Si3/Al sites → two Si3/Al sites and one Mg1 site. The calculated elastic constants of the considered β″ phases suggest that they are all mechanically stable, and all β″ phases are ductile. When Cu atoms replace Al atoms at Si3/Al sites in β″ phases, the values of bulk modulus (B), shear modulus (G), and Young’s modulus (E) all increase. The calculation of the phonon spectrum shows that Mg_4+xAl_2−xCuSi₄ (x = 0, 1) are also dynamically stable. The electronic structure analysis shows that the bond between the Si atom and the Cu atom has a covalent like property. The incorporation of the Cu atom enhances the electron interaction between the Mg2 and the Si3 atom so that the Mg2 atom also joins the Si network, which may be one of the reasons why Cu atoms increase the structure stability of the β″ phases.     

Magnetic and Electrical Behaviors of the Homo- and Heterometallic 1D and 3D Coordination Polymers Based on the Partial Decomposition of the [Cr(C2O4)3]3− Building Block

One-dimensional (1D) oxalate-bridged homometallic {[Mn(bpy)(C₂O₄)]·1.5H₂O}_n (1) (bpy = 2,2’-bipyridine) and heterodimetallic {[CrCu₃(bpy)₃(CH₃OH)(H₂O)(C₂O₄)₄][Cu(bpy)Cr(C₂O₄)₃]·CH₂Cl₂·CH₃OH·H₂O}_n (2) coordination polymers, as well as the three-dimensional (3D) heterotrimetallic {[CaCr₂Cu₂(phen)₄(C₂O₄)₆]·4CH₃CN·2H₂O}_n (3) (1,10-phenanthroline) network, have been synthesized by a building block approach using a layering technique, and characterized by single-crystal X-ray diffraction, infrared (IR) and impedance spectroscopies and magnetization measurements. During the crystallization process partial decomposition of the tris(oxalato)chromate(III) happened and 1D polymers 1 and 2 were formed. The antiferromagnetic interactions between the manganese(II) ions were mediated by oxalate ligands in the chain [Mn(bpy)(C₂O₄)]_n of 1, with intra-chain super-exchange interaction 𝐽 = (−3.134 ± 0.004) K; magnetic interaction between neighbouring chains is negligible making this system closer than other known Mn-chains to the ideal 1D Heisenberg antiferromagnet. Compound 2 comprises a 1D coordination anion [Cu(bpy)Cr(C₂O₄)₃]_nⁿ⁻ (Cr2–Cu4) with alternating [Cr(C₂O₄)₃]³⁻ and [Cu(bpy)]²⁺ units mutually bridged through the oxalate group. Another chain (Cr1–Cu3) is similar, but involves a homodinuclear unit [Cu(bpy)(H₂O)(µ-C₂O₄)Cu(bpy)(CH₃OH)]²⁺ (Cu1–Cu2) coordinated as a pendant group to a terminal oxalate oxygen. Magnetic measurements showed that the Cu1−Cu2 cationic unit is a strongly coupled antiferromagnetic dimer, independent from the other magnetic ions within ferromagnetic chains Cr1–Cu3 and Cr2–Cu4. A 3D polymer {[CaCr₂Cu₂(phen)₄(C₂O₄)₆]·4CH₃CN·2H₂O}_n (3) comprising three different metal centers (Ca²⁺, Cr³⁺ and Cu²⁺) oxalate-bridged, contains Ca²⁺ atoms as nodes connected with four Cr³⁺ atoms through oxalate ligands. The network thus formed can be reduced to an underlying graph of diamondoid (dia) or (6⁶) topology. Magnetization of 3 shows the ferromagnetic oxalate-bridged dimers [Cu^IICr^III], whose mutual interaction could possibly originate through the spin polarization of Ca²⁺ orbitals. Compounds 1 and 3 exhibit lower electrical conductivity at room temperature (RT) in comparison to compound 2.     

Boost the Crystal Installation and Magnetic Features of Cobalt Ferrite/M-Type Strontium Ferrite Nanocomposites Double Substituted by La3+ and Sm3+ Ions (2CoFe2O4/SrFe12−2xSmxLaxO19)

Spinel cobalt ferrite/hexagonal strontium hexaferrite (2CoFe₂O₄/SrFe_12−2xSm_xLa_xO₁₉; x = 0.2, 0.5, 1.0, 1.5) nanocomposites were fabricated using the tartaric acid precursor pathway, and the effects of La³⁺–Sm³⁺ double substitution on the formation, structure, and magnetic properties of CoFe₂O₄/SrFe_12−2xSm_xLa_xO₁₉ nanocomposite at different annealing temperatures were assayed through X-ray diffraction, scanning electron microscopy, and vibrating sample magnetometry. A pure 2CoFe₂O₄/SrFe₁₂O₁₉ nanocomposite was obtained from the tartrate precursor complex annealed at 1100 °C for 2 h. The substitution of Fe³⁺ ion by Sm³–⁺La³⁺ions promoted the formation of pure 2CoFe₂O₄/SrFe₁₂O₁₉ nanocomposite at 1100 °C. The positions and intensities of the strongest peaks of hexagonal ferrite changed after Sm³⁺–La³⁺ substitution at ≤1100 °C. In addition, samples with an Sm³⁺–La³⁺ ratio of ≥1.0 annealed at 1200 °C for 2 h showed diffraction peaks for lanthanum cobalt oxide (La₃Co₃O₈; dominant phase) and samarium ferrite (SmFeO₃). The crystallite size range at all constituent phases was in the nanocrystalline range, from 39.4 nm to 122.4 nm. The average crystallite size of SrFe₁₂O₁₉ phase increased with the number of Sm³⁺–La³⁺ substitutions, whereas that of CoFe₂O₄ phase decreased with an x of up to 0.5. La–Sm co-doped ion substitution increased the saturation magnetization (Ms) value and the subrogated ratio to 0.2, and the Ms value decreased with the increasing number of double substitutions. A high saturation magnetization value (Ms = 69.6 emu/g) was obtained using a La³⁺–Sm³⁺ co-doped ratio of 0.2 at 1200 for 2 h, and a high coercive force value (Hc = 1192.0 Oe) was acquired using the same ratio at 1000 °C.     

Molecular mechanical studies of DNA flexibility: Coupled backbone torsion angles and base-pair openings

Molecular mechanics studies have been carried out on “B-DNA-like” structures of [d(C-G-C-G-A-A-T-T-C-G-C-G)]₂ and [d(A)]₁₂·[d(T)]₁₂. Each of the backbone torsion angles (ψ, , ω, ω′, ′) has been “forced” to alternative values from the normal B-DNA values (g⁺, t, g^-, g^-, t conformations). Compensating torsion angle changes preserve most of the base stacking energy in the double helix. In a second part of the study, one purine N3-pyrimidine N1 distance at a time has been forced to a value of 6 Å in an attempt to simulate the base opening motions required to rationalize proton exchange data for DNA. When the 6-Å constraint is removed, many of the structures revert to the normal Watson-Crick hydrogen-bonded structure, but a number are trapped in structures ≈5 kcal/mol higher in energy than the starting B-DNA structure. The relative energy of these structures, some of which involve a non-Watson-Crick thymine C2(carbonyl)[unk]adenine 6NH₂ hydrogen bond, are qualitatively consistent with the ΔH for a “base pair-open state” suggested by Mandal et al. of 4-6 kcal/mol [Mandal, C., Kallenbach, N. R. & Englander, S. W. (1979) J. Mol. Biol. 135, 391-411]. The picture of DNA flexibility emerging from this study depicts the backbone as undergoing rapid motion between local torsional minima on a nanosecond time scale. Backbone motion is mainly localized within a dinucleoside segment and generally not conformationally coupled along the chain or across the base pairs. Base motions are much smaller in magnitude than backbone motions. Base sliding allows imino N—H exchange, but it is localized, and only a small fraction of the N—H groups is exposed at any one time. Stacking and hydrogen bonding cause a rigid core of bases in the center of the molecule accounting for the hydrodynamic properties of DNA.     

Encapsulated-guest rotation in a self-assembled heterocapsule directed toward a supramolecular gyroscope

The self-assembled heterocapsule 1·2, which is formed by the hydrogen bonds of tetra(4-pyridyl)-cavitand 1 and tetrakis(4-hydroxyphenyl)-cavitand 2, encapsulates 1 molecule of guests such as 1,4-diacetoxybenzene 3a, 1,4-diacetoxy-2,5-dimethylbenzene 3b, 1,4-diacetoxy-2,5-dialkoxybenzenes (3c, OCH₃; 3d, OC₂H₅; 3e, OC₃H₇; 3f, OC₄H₉; 3g, OC₅H₁₁; 3h, OC₆H₁₃; 3i, OC₈H₁₇), 1,4-diacetoxy-2,5-difluorobenzene 4a, and 1,4-diacetoxy-2,3-difluorobenzene 4b. The X-ray crystallographic analysis of 3c@(1·2) showed that the acetoxy groups at the 1,4-positions of 3c are oriented toward the 2 aromatic cavity ends of 1·2 and that 3c can rotate along the long axis of 1·2. Thus, the 1·2 (stator) with the encapsulation guest (rotator) behaves as a supramolecular gyroscope. A variable temperature (VT) ¹H NMR study in CDCl₃ showed that 3a, 3b, 4a, and 4b within 1·2 rotate rapidly even at 218 K, whereas guest rotation is almost inhibited for 3h and 3i even at 323 K. In this respect, 4b with a large dipole moment is a good candidate for the rotator of 1·2. For 3c–3g, the enthalpic (ΔH^‡) and entropic (ΔS^‡) contributions to the free energy of activation (ΔG^‡) for the guest-rotational steric barriers within 1·2 were obtained from Eyring plots based on line-shape analysis of the VT ¹H NMR spectra. The value of ΔG^‡ increased in the order 3c < 3d < 3e < 3f < 3g. Thus, the elongation of the alkoxy chains at the 2,5-positions of 3 puts the brakes on guest rotation within 1·2.     

Noninvasive 31P NMR probes of free Mg2+, MgATP, and MgADP in intact Ehrlich ascites tumor cells

³¹P NMR spectra of Ehrlich ascites tumor cells, suspended in a physiological medium, show well-defined αP, βP, and γP resonances of intracellular ATP. A comparison of the separation of 360 ± 1 Hz between the resonances of αP and βP in intact cells with the corresponding separations of 349 ± 0.5 and 438 ± 1 Hz in noncellular MgATP and ATP standards, measured at 10°C and 40.5 MHz NMR frequency, reveals that 88% of the total intracellular ATP (3.3 mM) is complexed to Mg²⁺. The corresponding value for intracellular free Mg²⁺ is 0.44 μmol/ml out of a total Mg²⁺ content of 8.5 μmol/ml cell water. A similar value of free Mg²⁺ is obtained from a comparison of the separation of 560 ± 1 Hz between the βP and γP resonances of intracellular ATP with the corresponding values of 552 ± 0.5 and 621 ± 1 Hz in noncellular MgATP and ATP standards. The fraction of total cellular ATP complexed to Mg²⁺ decreased to 80% in tumor cells incubated in a medium containing adenosine, glucose, and P_i without Mg²⁺, the corresponding level of intracellular free Mg²⁺ being significantly lower (0.24 mM) than that in the unincubated cells. With Mg²⁺ present in the incubation medium, MgATP and total Mg²⁺ levels increased by ≈2.5 mM, whereas with no added Mg²⁺, the MgATP increased 1.6 mM apparently at the expense of other Mg²⁺-complexed constituents since total Mg²⁺ remained essentially unchanged. At the measured levels of free Mg²⁺, intracellular ADP will be only 35-50% complexed to Mg²⁺. A knowledge of the state of Mg²⁺ complexation of ATP and ADP in intact Ehrlich tumor cells allows an accurate estimation of the phosphorylation potential and the extent of deviation of the mass action ratio ([MgATP][AMP]_f/[MgADP][ADP]_f) in cells with high phosphorylation potential from the Mg²⁺-dependent equilibrium value of the adenylate kinase reaction. The significance of the free Mg²⁺ value measured by the noninvasive NMR method in relation to the existence of Mg²⁺ complexation and compartmentation in tumor cells is discussed.     

Adaptive design in regression and control

When y = M(x) + ε, where M may be nonlinear, adaptive regression designs of the levels x₁, x₂,... at which y₁, y₂,... are observed lead to asymptotically efficient estimates of the value θ of x for which M(θ) is equal to any desired value y^*. More importantly, these designs also make the “cost” of the observations, defined at the nth stage to be Σ₁ⁿ (x_i — θ)², to be of the order of log n instead of n, an obvious advantage in medical and other applications.     

Reactive and nonreactive quenching of O(1D) by the potent greenhouse gases SO2F2, NF3, and SF5CF3

A laser flash photolysis–resonance fluorescence technique has been employed to measure rate coefficients and physical vs. reactive quenching branching ratios for O(¹D) deactivation by three potent greenhouse gases, SO₂F₂(k₁), NF₃(k₂), and SF₅CF₃(k₃). In excellent agreement with one published study, we find that k₁(T) = 9.0 × 10^-11 exp(+98/T) cm³ molecule^-1 s^-1 and that the reactive quenching rate coefficient is k_1b = (5.8 ± 2.3) × 10^-11 cm³ molecule^-1 s^-1 independent of temperature. We find that k₂(T) = 2.0 × 10^-11 exp(+52/T) cm³ molecule^-1 s^-1 with reaction proceeding almost entirely (∼99%) by reactive quenching. Reactive quenching of O(¹D) by NF₃ is more than a factor of two faster than reported in one published study, a result that will significantly lower the model-derived atmospheric lifetime and global warming potential of NF₃. Deactivation of O(¹D) by SF₅CF₃ is slow enough (k₃ < 2.0 × 10^-13 cm³ molecule^-1 s^-1 at 298 K) that reaction with O(¹D) is unimportant as an atmospheric removal mechanism for SF₅CF₃. The kinetics of O(¹D) reactions with SO₂ (k₄) and CS₂ (k₅) have also been investigated at 298 K. We find that k₄ = (2.2 ± 0.3) × 10^-10 and k₅ = (4.6 ± 0.6) × 10^-10 cm³ molecule^-1 s^-1; branching ratios for reactive quenching are 0.76 ± 0.12 and 0.94 ± 0.06 for the SO₂ and CS₂ reactions, respectively. All uncertainties reported above are estimates of accuracy (2σ) and rate coefficients k_i(T) (i = 1,2) calculated from the above Arrhenius expressions have estimated accuracies of ± 15% (2σ).     

Crystal Structure,Spectroscopic Characterization,Antioxidant and Cytotoxic Activity of New Mg(II) and Mn(II)/Na(I) Complexes of Isoferulic Acid

The Mg(II) and heterometallic Mn(II)/Na(I) complexes of isoferulic acid (3-hydroxy-4-methoxycinnamic acid, IFA) were synthesized and characterized by infrared spectroscopy FT-IR, FT-Raman, electronic absorption spectroscopy UV/VIS, and single-crystal X-ray diffraction. The reaction of MgCl₂ with isoferulic acid in the aqueous solutions of NaOH resulted in synthesis of the complex salt of the general formula of [Mg(H₂O)₆]⋅(C₁₀H₉O₄)₂⋅6H₂O. The crystal structure of this compound consists of discrete octahedral [Mg(H₂O)₆]²⁺ cations, isoferulic acid anions and solvent water molecules. The hydrated metal cations are arranged among the organic layers. The multiple hydrogen-bonding interactions established between the coordinated and lattice water molecules and the functional groups of the ligand stabilize the 3D architecture of the crystal. The use of MnCl₂ instead of MgCl₂ led to the formation of the Mn(II)/Na(I) complex of the general formula [Mn₃Na₂(C₁₀H₇O₄)₈(H₂O)₈]. The compound is a 3D coordination polymer composed of centrosymmetric pentanuclear subunits. The antioxidant activity of these compounds was evaluated by assays based on different antioxidant mechanisms of action, i.e., with ^•OH, DPPH^• and ABTS^•+ radicals as well as CUPRAC (cupric ions reducing power) and lipid peroxidation inhibition assays. The pro-oxidant property of compounds was measured as the rate of oxidation of Trolox. The Mg(II) and Mn(II)/Na(I) complexes with isoferulic acid showed higher antioxidant activity than ligand alone in DPPH (IFA, IC₅₀ = 365.27 μM, Mg(II) IFA IC₅₀ = 153.50 μM, Mn(II)/Na(I) IFA IC₅₀ = 149.00 μM) and CUPRAC assays (IFA 40.92 μM of Trolox, Mg(II) IFA 87.93 μM and Mn(II)/Na(I) IFA 105.85 μM of Trolox; for compounds’ concentration 10 μM). Mg(II) IFA is a better scavenger of ^•OH than IFA and Mn(II)/Na(I) IFA complex. There was no distinct difference in ABTS^•+ and lipid peroxidation assays between isoferulic acid and its Mg(II) complex, while Mn(II)/Na(I) complex showed lower activity than these compounds. The tested complexes displayed only slight antiproliferative activity tested in HaCaT human immortalized keratinocyte cell line within the solubility range. The Mn(II)/Na(I) IFA (16 μM in medium) caused an 87% (±5%) decrease in cell viability, the Mg salt caused a comparable, i.e., 87% (±4%) viability decrease in a concentration of 45 μM, while IFA caused this level of cell activity attenuation (87% ± 5%) at the concentration of 1582 μM (significant at α = 0.05).