Effects of Solvent Composition and Temperature on K+–18-Crown-6 Complexation in Acetonitrile–Water Mixed Solvents

Complexation of K⁺ by 18-crown-6 ether (18C6) in pure water and in acetonitrile–water mixed solvents containing 0.1 mol-dm^{? 3} (C₂H₅)₄NCl has been systematically studied by isothermal titration calorimetry (ITC) at 293, 298, and 303 K. The formation constant K of the 1:1 [K(18C6)]⁺ complex and the complexation enthalpy Δ _rH were simultaneously determined from the titration data. The logK and Δ _rH(kJ-mol^{? 1}) values at 298 K are 2.04, ?26.2 in pure water and 2.23, ?25.0; 2.61, ?24.2; 2.95, ?23.8; 3.48, ?21.0; 3.85, ?19.4; 4.36, ?18.7; and 5.73, ?17.0 in the mixed solvents at x _AN (mole fraction of acetonitrile) of 0.043, 0.135, 0.258, 0.448, 0.578, 0.759, and 1.0, respectively. The change in heat capacity for the complex formation, Δ C _p °, was also determined by the temperature dependence of Δ _rH. Whereas the Δ C _p ° is (57 ± 11) and (63 ± 20) J-mol^{? 1}-K^{? 1} in pure water and in the solvent mixture at x _AN = 0.043, respectively, it decreases with increasing x _AN. The Δ C _p ° values are ?(48 ± 11), ?(110 ± 25), ?(354 ± 40), ?(359 ± 24), and ?(304 ± 30) J-mol^{? 1}-K^{? 1} at x _AN = 0.135, 0.258, 0.448, 0.578, and 0.759, respectively. The changes in complexation thermodynamics (Δ Δ _rG, Δ Δ_rH, and Δ Δ _r S) are discussed in terms of the corresponding transfer thermodynamics of K⁺, 18-crown-6, and [K(18C6)]⁺ upon transferring from water to acetonitrile–water mixed solvents. It was found that hydrophobic solvation of the complex [K(18C6)]⁺ plays an important role in complex formation occurring in water and in the water-rich mixed solvent. Moreover, changes in solvent structure significantly affect the transfer enthalpy and entropy of each species, i.e., K⁺, 18-crown-6, and [K(18C6)]⁺. The observed monotonous changes in the complexation Gibbs energy, enthalpy, and entropy with solvent composition are due to the effective compensation of the Δ _trG, Δ _trH, and Δ _tr S for K⁺ with those for 18-crown-6 and [K(18C6)]⁺.     

An evaluation of silica-supported catalysts for the reaction between ethanol and polymethylhydrogensiloxane

Catalysis of the reaction between Me₃SiO[Si(H)Me)O]_nSiMe₃ (n ≈ 50) and ethanol by silica-supported rhodium and iridium catalysts has been investigated. Donor groups in the anchored ligands were PPh₂, S^?, or C₅H₄^?. The rhodium-PPh₂ system showed marked inhibition by dihydrogen. The supported iridium catalysts all showed high activity which declined rapidly during successive cycles of re-use, but the iridium-PPh₂ catalyst was the least affected. In every case, the separated liquid products showed activity as homogeneous catalysts, indicating that leaching of the metal from the support was occurring. That ligand was also being leached was shown by labelling with tritium. The results demonstrate the necessity to test supported catalysts through more than one cycle.     

Theoretical studies of halocarbene cycloaddition selectivities: A new interpretation of negative activation energies and entropy control of selectivity

Ab initio RHF calculations with the 3–21G basis set have been carried out on cycloadditions of CF₂ and CCl₂ with ethylene. Although π-complex intermediates are predicted for both reactions at this level, MP2/3-21G calculations imply that there are no complexes in reactions of CCl₂ or more reactive carbenes with ethylene or substituted alkenes. Nevertheless, negative activation energies can be observed, since ΔG reaches a maximum due to the increase in —TΔS for these bimolecular reactions. The apparent “entropy control” for reactive carbenes results from the rapid decrease in ΔH. As the reactivity of the alkene increases, the transition state shifts to an earlier point on the free energy surface, where —TΔS³ is lower, but ΔH³ is higher than for less reactive alkenes. Model potentials are developed for ΔH and —TΔS which reproduce experimental behavior, without the assumption of intermediates.     

Resolving Entangled JH-H-Coupling Patterns for Steroidal Structure Determinations by NMR Spectroscopy

For decades, high-resolution ¹H NMR spectroscopy has been routinely utilized to analyze both naturally occurring steroid hormones and synthetic steroids, which play important roles in regulating physiological functions in humans. Because the ¹H signals are inevitably superimposed and entangled with various J_H–H splitting patterns, such that the individual ¹H chemical shift and associated J_H–H coupling identities are hardly resolved. Given this, applications of thess information for elucidating steroidal molecular structures and steroid/ligand interactions at the atomic level were largely restricted. To overcome, we devoted to unraveling the entangled J_H–H splitting patterns of two similar steroidal compounds having fully unsaturated protons, i.e., androstanolone and epiandrosterone (denoted as 1 and 2, respectively), in which only hydroxyl and ketone substituents attached to C3 and C17 were interchanged. Here we demonstrated that the J_H–H values deduced from 1 and 2 are universal and applicable to other steroids, such as testosterone, 3β, 21-dihydroxygregna-5-en-20-one, prednisolone, and estradiol. On the other hand, the ¹H chemical shifts may deviate substantially from sample to sample. In this communication, we propose a simple but novel scheme for resolving the complicate J_H–H splitting patterns and ¹H chemical shifts, aiming for steroidal structure determinations.     

Synthesis of the cyclic heptapeptide axinellin A

The first synthesis of the naturally occurring cyclic peptide axinellin A has been achieved. Cyclization and subsequent deprotection of linear precursors containing either a t-butyl protected Thr residue or a Thr(Ψ^Me,Mepro) derivative gave a cyclic peptide, identical in all respects to the naturally occurring material, with the exception that the synthetic peptide does not exhibit the cytotoxic activity reported for the natural product.     

A deuterium-labelling mass spectrometry–tandem diode-array detector screening method for rapid discovery of naturally occurring electrophiles

Because electrophiles regulate many signalling pathways in cells, by modifying cysteine residues in proteins, they have a wide range of biological activity. In this study, a deuterium-labelling mass spectrometry–tandem diode-array detector (MS–DAD) screening method was established for rapid discovery of naturally occurring electrophiles. Glutathione (GSH) was used as a probe and incubated with natural product extracts. To distinguish different types of electrophile, incubation was performed in two reaction solvents, H₂O and D₂O. Ten types of naturally occurring electrophile were chosen, on the basis of their properties, to undergo the screening assay. By using this screening method, we successfully discovered the bioactive electrophile 4-hydroxyderricin in an ethanol extract of Angelica keiskei. This electrophile had potent NAD(P)H:quinone oxidoreductase 1 (NQO1)-inducing activity at a concentration of 20 μmol L⁻¹.     

An ab initio study of the structure and torsional modes of the H2SO4 molecule

Ab initio calculations at the STO—3G and 4—31G levels have been carried out for the H₂SO₄ molecule as a function of the pair of twist angles of the HO bonds about the respective OS bonds. Values for the remaining bond angles and lengths were taken from the recent microwave structural determination by Kuczkowski et al. The results indicate a minimum energy for a structure with a (sc, sc) conformation and C₂ symmetry, where sc denotes synclinal, or gauche. This structure corresponds to that observed. At a higher energy of 11.5 kJ mol^?1 (4—31G) there is a structure with a (+sc, ?sc) conformation and C_s symmetry. The torsional modes corresponding to the a and b irreducible representations of the C₂ point group are estimated to have frequencies of 280 and 265 cm^?1, respectively.     

Electron Capture Dissociation of Hydrogen-Deficient Peptide Radical Cations

Hydrogen-deficient peptide radical cations exhibit fascinating gas phase chemistry, which is governed by radical driven dissociation and, in many cases, by a combination of radical and charge driven fragmentation. Here we examine electron capture dissociation (ECD) of doubly, [M + H]^2+?, and triply, [M + 2H]^3+?, charged hydrogen-deficient species, aiming to investigate the effect of a hydrogen-deficient radical site on the ECD outcome and characterize the dissociation pathways of hydrogen-deficient species in ECD. ECD of [M + H]^2+? and [M + 2H]^3+? precursor ions resulted in efficient electron capture by the hydrogen-deficient species. However, the intensities of c- and z-type product ions were reduced, compared with those observed for the even electron species, indicating suppression of N?CC_?? backbone bond cleavages. We postulate that radical recombination occurs after the initial electron capture event leading to a stable even electron intermediate, which does not trigger N?CC_?? bond dissociations. Although the intensities of c- and z-type product ions were reduced, the number of backbone bond cleavages remained largely unaffected between the ECD spectra of the even electron and hydrogen-deficient species. We hypothesize that a small ion population exist as a biradical, which can trigger N?CC_?? bond cleavages. Alternatively, radical recombination and N?CC_?? bond cleavages can be in competition, with radical recombination being the dominant pathway and N?CC_?? cleavages occurring to a lesser degree. Formation of b- and y-type ions observed for two of the hydrogen-deficient peptides examined is also discussed.     

A convenient synthesis of 2β,3α-dihydroxyurs-12-en-28-oic acid as a natural diastereoisomer of corosolic acid

2β,3α-Dihydroxyurs-12-en-28-oic acid（6） is a naturally occurring diastereoisomer of corosolic acid with glycogen phosphorylase inhibitory activity.A new strategy for the semi-synthesis of 6 was developed.Using the commercially available ursolic acid（1） as the starting materials,6 was synthesized through five facile reactions with a high stereoselectivity and an overall yield of 47.3%.The structure of 6 was confirmed by optical rotation.ESI-MS,¹H NMR and ¹³C NMR data.     

The structure of thorikosite,a naturally occurring member of the bismuth oxyhalide group

Thorikosite, (Pb₃Sb_0.6As_0.4)(O₃0H)Cl₂, is a naturally occurring member of the bismuth oxyhalide group isostructural with LiBi₃O₄Cl₂. The space group isI4/mmm witha = 3.919(1)A?,c = 12.854(5)A?, andZ = 1. A crystal structure analysis showed complete solid solution of Pb²⁺, Sb³⁺, and As³⁺ on the single cation site and large atomic temperature factors indicative of pervasive structural disorder. The latter is due to the structural adjustments necessary to accommodate cations of very different sizes in the same site. Thorikosite is closely related to synthetic tetragonal PbSbO₂Cl through the coupled substitution Sb³⁺O^2? ? Pb²⁺(OH)^?.     

Chemoenzymatic synthesis of highly enantiomerically enriched secondary alcohols with a thiazolic core

Stereoselective preparative enzymatic acylation and hydrolysis/methanolysis of various C-substituted rac-thiazol-2-yl-methanols were achieved for the preparation of enantiopure or enantiomerically enriched, naturally occurring 2-hydroxymethylthiazoles. The absolute configurations of the resulting secondary alcohols were determined by a detailed ¹H NMR study of Mosher’s derivatives.     

Host–guest complexation of antioxidative caffeic and ferulic acid amides with a functionalized cyclophane

Host?guest complexation has been studied by ¹H NMR on the benzyl and phenethyl amides of ferulic and caffeic acids as the guests in chloroform and acetonitrile; the counter host is a cyclophane which integrates four phenylene rings, amino and amide groups in the macrocyclic framework and bears four pendant methyl acetate ester arms. CAPE, one of the best known natural antioxidants, also has been studied for comparison. Among the guests studied, ferulic acid benzyl amide shows NMR shifts due to the formation of a host?guest complex in chloroform. The complexation occurs in two steps with the formation constants K ₁?=?[HG]/[H][G]?=?6?M^?1 and β ₂?=?[HG₂]/[H][G]²?=?87?M^?2. Two guest molecules are bound on the surface of the macrocyclic framework of a host molecule by two hydrogen bonds, NH(host amide)···O=C(guest amide) and C=O(host ester)···HO(guest phenol). The latter hydrogen bond may protect the bioactive site, i.e., phenol OH, of guest molecules captured in the complex against undesirable oxidation. This feature is observed only for ferulic acid benzyl amide in chloroform; the cyclophane ester interacts with this amide, distinctively from the other hydroxycinnamic acid derivatives.     

Temperature dependences of J(C,H) and J(C,D) in 13CH4 and some of its deuterated isotopomers

The nuclear spin—spin coupling constants J(C,H) and J(C,D) have been measured over the temperature range 200–370 K for the methane isotopomers ¹³CH₄, ¹³CH₃D, ¹³CHD₃ and ¹³CD₄. The coupling constants increase with increasing temperature for any one isotopomer and decrease with increasing secondary deuterium substitution at any one temperature. The results are entirely attributable to intramolecular effects and the data have been fitted by a weighted least-squares regression analysis to a spin—spin coupling surface thereby yielding a value for ¹J_e(C,H), the coupling constant at equilibrium geometry, and values for the bond length derivatives of the coupling. We find that ¹J_e(C,H) = 120.78 (±0.05) Hz which is about 4.5 Hz smaller than the observed value in ¹³CH₄ gas at room temperature. Results are also reported for J(H,D) in ¹³CH₃D and ¹³CHD₃ for which no temperature dependence was detected.     

Metallocene–methylaluminoxane catalysts for olefin polymerizations. III. Reduction of η5-cyclopentadienyl trichlorides of titanium and zirconium

The reactions occurring between the components of metallocene and methylaluminoxane (MAO) catalyst leading to the reduction of the former were studied by electron paramagnetic resonance (EPR). At low Al/Zr ratios, C_pZrCl₃ (C_p = η⁵-cyclopentadienyl) was reduced to simple trivalent Zr species (g = 1.998, a(⁹¹Zr) = 12.3 G) without other superhyperfine splittings. At higher Al/Zr ratios the reactions proceed further to form two CpZr(III) hydrides (g = 1.991, a(H) = 5.5 G; and g = 2.00, a(H) = 3 G). Two CpTi(III) hydrides were also produced by the reaction of MAO with CpTiCl₃ (g = 1.989, a(H) = 7.4 G, a(Ti) = 8 G; and, g = 1.995, a(H) = 4.5 G, a(Ti) = 8 G). In the case of Cp^*TiCl₃ (Cp^* = η⁵-pentamethyl cyclopentadienyl) initially a multitude of paramagnetic species were formed. After long reaction time the final products show EPR features consistent with two η³: η⁴-(1,2,3-trimethyl-4,5-dimethylene cyclopentadienyl)hydrido Ti(III) species: the abundant one with g = 1.999, (H, sextet) = 9.5 G, a(Ti) = 9.5 G, and a weaker one of g = 1.975, a(H) = 4.8 G. All the five protons of these species and as well as those in the Cp hydrido complexes of Ti and Zr undergo facile H? D exchanges with D₂. MAO is important in the formation of these hydrides because they are not formed by trimethyl aluminum reduction. The presence of tetrahydrofuran suppresses the hydride formation. The possible structures for the hydrido species and reactions producing them are discussed.     

Cyclometalated Iridium(III) Complex–Cationic Peptide Hybrids Trigger Paraptosis in Cancer Cells via an Intracellular Ca2+ Overload from the Endoplasmic Reticulum and a Decrease in Mitochondrial Membrane Potential

In our previous paper, we reported that amphiphilic Ir complex–peptide hybrids (IPHs) containing basic peptides such as KK(K)GG (K: lysine, G: glycine) (e.g., ASb-2) exhibited potent anticancer activity against Jurkat cells, with the dead cells showing a strong green emission. Our initial mechanistic studies of this cell death suggest that IPHs would bind to the calcium (Ca²⁺)–calmodulin (CaM) complex and induce an overload of intracellular Ca²⁺, resulting in the induction of non-apoptotic programmed cell death. In this work, we conduct a detailed mechanistic study of cell death induced by ASb-2, a typical example of IPHs, and describe how ASb-2 induces paraptotic programmed cell death in a manner similar to that of celastrol, a naturally occurring triterpenoid that is known to function as a paraptosis inducer in cancer cells. It is suggested that ASb-2 (50 µM) induces ER stress and decreases the mitochondrial membrane potential (ΔΨ_m), thus triggering intracellular signaling pathways and resulting in cytoplasmic vacuolization in Jurkat cells (which is a typical phenomenon of paraptosis), while the change in ΔΨ_m values is negligibly induced by celastrol and curcumin. Other experimental data imply that both ASb-2 and celastrol induce paraptotic cell death in Jurkat cells, but this induction occurs via different signaling pathways.     

Microwave and vibrational spectra, ab initio calculations, conformational stabilities and assignments of the fundamentals of the Cs conformer of n-butylgermane

The FT-microwave spectrum of n-butylgermane, CH₃CH₂CH₂CH₂GeH₃ has been investigated from 4000 to 18,000 MHz and the microwave spectra have been observed for all of the five naturally occurring germanium isotopologues for the anti-anti (aa) conformer. The dipole moment for the ⁷⁴Ge containing species has been measured, giving a total dipole moment of 0.881 (26) D. In addition, the vibrational spectrum of n-butylgermane is described. Modestly complete assignments are made for the aa conformer. The relative stabilities of the five conformers are calculated, and the anti-anti (aa) conformer is found to be the most stable in all calculations done. This conclusion is confirmed by the infrared and Raman spectrum of the annealed crystal. The dipole moments of all conformers are calculated to be approximately equal and less than 1 D, ranging from approximately 0.8 to 0.9 D.     

OH stretching force constants in complexes of water with F−, Cl−, Li+ ions and LiF,LiCl ion pairs by 6-31G ab initio MO calculations

Ab initio MO calculations using 6-31G and 6-31 + G (for complexes with F⁻ and LiF) basis sets have been carried out for complexes of H₂O (monomer and dimer) with F⁻, Cl⁻, Li⁺ ions as well as with LiF and LiCl ion pairs for the evaluation of the OH stretching force constants. The changes in force constants are discussed in terms of molecular interactions, cooperativity effect and interionic electrostatic interactions. It is noticed that the cooperativity effect also operates through ionic bonds in symmetrically hydrated ion pairs and that OH stretching force constants are found to increase in the case of solvent bound ion pairs and symmetrically hydrated halide ions showing anticooperativity effect.     

Theoretical investigations on nonlinear optical and spectroscopic properties of 6-(3,3,4,4,4-pentafluoro-2-hydroxy-1-butenyl)-2,4-pyrimidinedione: An efficient NLO material

In this study, quantum chemical calculations of geometric parameters, conformational, natural bond orbital (NBO) and nonlinear optical (NLO) properties, vibrational frequencies, ¹H and ¹³C NMR chemical shifts of the title molecule [C₉H₇F₅N₂O₃] in the ground state have been calculated with the help of Density Functional Theory (DFT-B3LYP/6-311++G(d,p)) and Hartree-Fock (HF/6-311++G(d,p)) methods. The optimized geometric parameters, vibrational frequencies, ¹H and ¹³C NMR chemical shifts values are compared with experimental values of the investigated molecules. Comparison between experimental and theoretical results showed that B3LYP/6-311++G(d,p) method is able to provide more satisfactory results. In order to understand this phenomenon in the context of molecular orbital picture, we examined the molecular frontier orbital energies (HOMO, HOMO-1, LUMO, and LUMO + 1), the energy difference (ΔE) between E _HOMO and E _LUMO, electronegativity (χ), hardness (η), softness (S) calculated by HF/6-311++G(d,p) and B3LYP/6-311++G(d,p) levels. The molecular surfaces, Mulliken, NBO, and Atomic polar tensor (APT) charges of the investigated molecule have also been calculated by using the same methods.     

Diffusion of hydrogen isotopes and their mutual perturbation in Ti0.33V0.67HxDy (x+y≈0.9) studied by H and H NMR

Ti_0.33V_0.67H_xD_y (x+y≈0.9) alloys have been studied by means of X-ray powder diffraction (XRD), differential scanning calorimetry (DSC) and ¹H and ²H NMR. The crystal structures are body-centered-cubic (bcc) dominantly, being mixed with a face-centered-cubic (fcc) phase. A phase transition similar to that from the δ_D phase to the α_D phase in the V-D system is observed in all the samples except for the protide. H and D are considered to occupy tetrahedral sites. The temperature and frequency dependence of spin-lattice relaxation times T₁ of ¹H and ²H has been analyzed by Bloembergen-Purcell-Pound equations with a distribution of correlation times, and parameters of hydrogen diffusion are estimated. The mean activation energy for D diffusion (E_D) is higher than that for H diffusion (E_H). E_H is constant while E_D increases slightly with the [D]/[H] ratio. The distribution of the correlation times increases as the [D]/[H] ratio decreases.