Thermodynamic,structural and dynamic properties of ionic liquids [C4mim][CF3COO], [C4mim][Br] in the condensed phase,using molecular simulations

In this work a series of thermodynamic, structural, and dynamical properties for the 1-butyl-3-methylimidazolium trifluoroacetate ([C₄mim][CF₃COO]) and 1-butyl-3-methylimidazolium bromide, ([C₄mim][Br]) ionic liquids (ILs) were calculated using Non-polarizable Force Fields (FF), parameterized using a methodology developed previously within the research group, for condensed phase applications. Properties such as the Vapor-Liquid Equilibrium (VLE) curve, critical points (ρ_c, T_c), Radial, Spatial and Combined Distribution Functions and self-diffusion coefficients were calculated using Equilibrium Molecular Dynamics simulations (EMD); other properties such as shear viscosities and thermal conductivities were calculated using Non-Equilibrium Molecular Dynamics simulations (NEMD). The results obtained in this work indicated that the calculated critical points are comparable with those available in the literature. The calculated structural information for these two ILs indicated that the anions interact mainly with hydrogen atoms from both the imidazolium ring and the methyl chain; the bromide anion displays twice the hydrogen coordination number than the oxygen atoms from the trifluoroacetate anion. Furthermore, Non-Covalent interactions (NCI index), determined by DFT calculations, revealed that some hydrogen bonds in the [C₄mim][Br] IL displayed similar strength to those in the [C₄mim][CF₃COO] IL, in spite of the shorter O⁻–H distances found in the latter IL. The majority of the calculated transport properties presented reasonable agreement with the experimental available data. Nonetheless, the self-diffusion coefficients determined in this work are under-estimated with respect to experimental values; however, by escalating the electrostatic atomic charges for the anion and cation to ±0.8e, only for this property, a remarkable improvement was obtained. Experimental evidence was recovered for most of the calculated properties and to the best of our knowledge, some new predictions were done mainly in thermodynamic states where data are not available. To validate the FF, developed previously within the research group, dynamic properties were also evaluated for a series of ILs such as [C₄mim][PF₆], [C₄mim][BF₄], [C₄mim][OMs], and [C₄mim][NTf₂] ILs.

Non-covalent interactions, coordination numbers, RDFs, SDFs, CDFs, and transport properties for the [C₄mim][Br] and [C₄mim][CF₃COO] ionic liquids were determined.     

Red/green-light emission in continuous dielectric phase transition materials: [Me3NVinyl]2[MnX4] (X = Cl,Br)

The luminescence of dielectric phase transition materials is one important property for technological applications, such as low-energy electron excitation. The combination of dielectric phase transitions and luminescence within organic–inorganic hybrids would lead to a new type of luminescent dielectric phase transition multifunctional material. Here, we report two novel A₂BX₄ organic–inorganic hybrid complexes [Me₃NVinyl]₂[MnCl₄] 1 and [Me₃NVinyl]₂[MnBr₄] 2, ([Me₃NVinyl] = trimethylvinyl ammonium cation). The complexes 1 and 2 were found to undergo continuous reversible phase transitions as well as switch dielectric phase transitions. Strikingly, intensive red luminescence and green luminescence were obtained under UV excitation respectively to reveal potential application of the two complexes in multi-functional materials along with dielectric switches and so on.

The luminescence of dielectric phase transition materials is one important property for technological applications, such as low-energy electron excitation.     

The physicochemical properties of a room-temperature liquidus binary ionic liquid mixture of [HNMP][CH3SO3]/[Bmim]Cl and its application for fructose conversion to 5-hydroxymethylfurfural

Via heating first and then cooling, binary ionic liquid (IL) mixture of N-methyl-2-pyrrolidonium methylsulfonate ([HNMP][CH₃SO₃]) and 1-butyl-3-methylimidazolium chloride ([Bmim]Cl) could form a liquid at room temperature. The glass-transition temperature (T_g) characterized by DSC depends on its composition with T_g being as low as −63 °C. The physicochemical properties of the binary IL mixtures also vary with the composition. With the increase of the mole fraction of [Bmim]Cl, the hydrogen-bond accepting ability (β) of the binary IL mixture increases, but the hydrogen-bond donating ability (α) deceases. In this binary IL mixture, fructose could be effectively converted into 5-hydroxymethylfurfural (HMF) at room temperature. The HMF yields at a given time are found to be well correlated with the physicochemical properties of the binary mixture, especially the α and β values. Under specified conditions, the present IL mixture as medium for fructose dehydration into HMF is comparable to the medium formed by ILs and alcohol, where the alcohols have negative effect on the HMF formation.

A liquidus mixture of [HNMP][CH₃SO₃]/[Bmim]Cl has been characterized and tried as medium for room-temperature conversion of fructose into HMF.     

Effect of methylene chain length of perovskite-type layered [NH3(CH2)nNH3]ZnCl4 (n = 2, 3, and 4) crystals on thermodynamic properties,structural geometry,and molecular dynamics

The structure of organic–inorganic perovskite [NH₃(CH₂)₄NH₃]ZnCl₄ was determined; the lattice constants with monoclinic structure were determined to be a = 7.2527 Å, b = 8.1101 Å, c = 10.3842 Å, and β = 80.3436°. The crystal was almost thermally stable up to approximately 560 K. The endothermic peaks at 481 K and 506 K were assigned to the phase transition of the material. In addition, the structural characteristics and molecular dynamics of the cation were studied via magic angle spinning nuclear magnetic resonance experiments. Based on the results, the effects of the length of the CH₂ group in the cation of the [NH₃(CH₂)_nNH₃]ZnCl₄ (n = 2, 3, and 4) crystals were considered. Regardless of whether n was even or odd, the differences in the thermal and physical properties were minimal. Moreover, a difference in molecular motion relative to the length of the cation was observed only at high temperatures. These results provide useful information about the thermal stability and molecular dynamics of [NH₃(CH₂)_nNH₃]ZnCl₄ crystals and are expected to facilitate potential applications of such compounds in supercapacitors, batteries, and fuel cells.

¹H NMR spin–lattice relaxation times T_1ρ of [NH₃(CH₂)_nNH₃]ZnCl₄ (n = 2, 3, and 4) as a function of inverse temperature. The solid lines represent activation energy.     

Binding of calcium by organic anions, determined by perturbation of the equilibrium solubility of [14C]calcium oxalate

Confirmation is needed of the reported binding of calcium ions (Ca2+) by bile salts, which is believed to decrease the activity of free calcium ions [Ca2+] available for precipitation of insoluble calcium salts of organic anions in pigment gallstones. We report a new method to determine the association constants (K'f) of calcium for organic anions, from the perturbation by the added anion of the equilibrium solubilization of calcium [14C]oxalate monohydrate crystals (CaOx*). CaOx* crystals were prepared by stepwise conversion of [14C]oxalic acid to its K+ and Ca2+ salts. Structure and purity were confirmed by X-ray diffraction of the crystals. CaOx* was incubated (37 degrees C, under N2) in 0.15 M NaCl in CO2-free deionized H2O at pH 6.3. Dissolution of CaOx*, estimated by radioassay of the 0.22-micron Millipore filtrate, attained equilibrium at 3 days, with K'sp = [Ca2+] * [Ox=] = 2.34 X 10(-8) M2, calculated using known affinity constants for the soluble complexes of NaOx- (K'NaOx = 3.215 M-1) and CaOx (K'CaOx = 195.0 M-1). Keeping total [Na+] = 0.15 M, we added anions that formed soluble complexes with Ca2+. This decreased free [Ca2+], causing more CaOx* to dissolve in amounts related to the concentration of added anion and its K'f for Ca2+. With this method, K'f values for citrate, malonate and malate were similar to the values we determined with the Ca2+ ion electrode, and to published values obtained with the Ca2+ ion electrode and other methods. The sensitivity of the CaOx method permits determination of K'f values with small quantities and low concentrations of the anions and calcium.     

Long range deuterium isotope effects on 13C NMR chemical shifts of 2-alkanones in CD3OD solutions of imidazolium acetate ionic liquids

Deuterium isotope substitution in one part of a molecule could produce a significant effect on chemical shifts of neighbouring nuclei as well as on nuclei, located far from the site of replacement. To estimate how far this influence could extend the reaction of proton–deuterium exchange of several 2-alkanones in deuterated methanol solutions of 1-methyl 3-ethyl imidazolium acetate ionic liquid (IL) was studied in detail using ¹³C NMR spectroscopy. Deuteration occurs in alkyl groups of 2-alkanones neighboring the ketonic group via keto–enol tautomerization catalyzed by IL. In the course of the reaction, various isotopomers with various deuteration levels are formed, among which a dynamic equilibrium is established. The number of substituted deuterons affects not only the multiplicity and chemical shifts of directly bonded carbon, but carbons in the groups further along the alkyl chain. Moreover, the latter groups better indicate the level and site of substitution.

Long range deuterium isotope effects on the carbon spectral pattern in 2-hexanone reveal the existence and distribution of H/D isotopomers.     

Tissue distribution and functional correlation of [3H]leukotriene C4 and [3H]leukotriene D4 binding sites in guinea-pig uterus and lung preparations

To determine the distribution of leukotriene (LT) C4 and LTD4 receptors and functional significance of each receptor, we used [3H]LTC4 and [3H]LTD4 to measure the binding activity in various tissue homogenates and to correlate the relative ability of the LT agonists to inhibit binding with their contractile responses in guinea-pig uterine or lung parenchymal preparations. Guinea-pig brain contained the highest binding activity of 1 to 2 nM [3H] LTC4 followed by small intestine, heart, lung, kidney, uterus, etc., whereas guinea-pig lung had at least 2.7-fold greater [3H] LTD4 binding activity than any other tissues tested. In the brain and uterine homogenates, the rank order of potency for the compounds in competing with [3H]LTC4 for binding sites was LTC4 much greater than LTD4 greater than LTE4 greater than FPL-55712 = arachidonic acid. The in vitro functional study showed that the ability of the LT agonists to produce uterine contraction was in the order of LTC4 greater than LTD4 greater than LTE4, which is compatible with their relative effect for inhibition of uterine or brain [3H]LTC4 binding. In the lung homogenate, either LTC4, LTD4 or LTE4 inhibited effectively [3H]LTD4 binding and the potency order for the [3H]LTD4 competition study was LTD4 greater than LTE4 greater than LTC4 much greater than FPL-55712 greater than arachidonic acid. These LT agonists also produced lung contraction effectively and the difference among their contractile ability was not significant. We conclude that 1) there are distinct functional LTC4 and LTD4 receptors, 2) activation of the LTC4 receptor could account for the uterine contraction due to the LT agonists and 3) the lung contraction induced by LTC4, LTD4 and LTE4 is at least mediated partly by the LTD4 receptor.     

Pulmonary extraction of [3H]bupivacaine: modification by dose, propranolol and interaction with [14C]5-hydroxytryptamine

The authors studied the single-pass pulmonary extraction of the potent local anesthetic, bupivacaine, in 21 anesthetized rabbits. Pulmonary extraction of [3H]bupivacaine and [14C]5-hydroxytryptamine (5-HT) was quantified from multiple indicator-dilution outflow curves using indocyanine green as the intravascular reference substance. Pulmonary extraction at control (n = 15; mean +/- S.D.) was 81 +/- 6 and 78 +/- 9% for [3H]bupivacaine and [14C]5-HT, respectively. The apparent volume of distribution of bupivacaine was 38 +/- 9 ml/kg compared with 12 +/- 4 ml/kg for indocyanine green. Simultaneous administration of up to 300 micrograms/kg of bupivacaine did not affect the disposition of either radiolabeled amine; however, injection of 1000 micrograms/kg of bupivacaine significantly (P less than .01) depressed pulmonary extraction of both [3H]bupivacaine and [14C]5-HT. In the presence of 1000 micrograms/kg bupivacaine, the apparent volume of distribution of [3H]bupivacaine decreased to 24 +/- 9 ml/kg (P less than .01). Fifteen minutes after administration of propranolol (100-250 micrograms/kg i.v.), [14C]5-HT removal was unchanged, but the pulmonary extraction of [3H]bupivacaine was significantly decreased to 70 +/- 12% (n = 6; P less than .01). These data suggest that bupivacaine is extensively removed as it enters the lung and that the removal process is a combination of passive diffusion and a small component of saturable specific binding. The interaction of bupivacaine with 5-HT may be part of this specific binding (i.e., endothelial cell uptake) or may have been secondary to direct effects of large concentrations of bupivacaine on membrane function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thermal,ferroelastic, and structural properties near phase transitions of organic–inorganic perovskite type [NH3(CH2)3NH3]CdBr4 crystals

Hybrid perovskites have potential applications in several electrochemical devices such as supercapacitors, batteries, and fuel cells. Therefore, we studied the thermal behavior and structural dynamics of organic–inorganic hybrid perovskite [(NH₃)(CH₂)₃(NH₃)]CdBr₄ crystals near phase transition temperatures, T_C2 (=328 K) and T_C1 (=363 K), which are correlated to the structural dynamics of cations and anions. The structural geometry and molecular dynamics with emphasis on the role of the [(NH₃)(CH₂)₃(NH₃)] cation and CdBr₆ anion were discussed in terms of MAS ¹H NMR, MAS ¹³C NMR, ¹⁴N NMR, and ¹¹³Cd NMR as a function of the temperature. The environments surrounding ¹H, ¹³C, ¹⁴N, and ¹¹³Cd are investigated near T_C1 and T_C2 using these results. Spin–lattice relaxation times T_1ρ were discussed in terms of the change in temperature. The discontinuous changes of ¹H T_1ρ and ¹³C T_1ρ near T_C1 are consistent with the change of the lattice constant. Shorter T_1ρ values at high temperature indicate that ¹H and ¹³C in the organic chains are more flexible at these temperatures. Based on these results, the physicochemical properties of the cation and anion during the III–II–I phase transitions were discussed. This study was conducted to improve the relatively weak thermal stability compared to the high efficiency for a variety of applications.

We studied the thermal behavior and structural dynamics of [NH₃(CH₂)₃NH₃]CdBr₄ near phase transition temperatures.     

Single-pass removal of [14C]-5-hydroxytryptamine and [3H]norepinephrine by rabbit lung, in vivo: kinetics and sites of removal

Multiple indicator dilution techniques were employed to study the kinetics and sites of removal of [14C]-5-hydroxytryptamine (5-HT) and [3H]norepinephrine (NE) by rabbit lung in vivo. Percentage of single-pass transpulmonary removal of 5-HT decreased from 87 +/- 2 to 73 +/- 3, 49 +/- 7 and 34 +/- 2% when the total dose of administered 5-HT was increased from 8 X 10(-9) to 30, 75 and 150 X 10(-9) mol, respectively. Similarly, percentage of removal of NE decreased from 23 +/- 2 to 18 +/- 2, 1 +/- 2 and 5 +/- 2% when the amount of NE administered was increased from 0.3 X 10(-9) to 10, 50 and 100 X 10(-9) mol, respectively. From these data, kinetic constants of removal were calculated assuming either homogeneous or heterogeneous pulmonary perfusion; values for the apparent Michaelis-Menten constant (Km) averaged 1.1 +/- 0.4 X 10(-6) M (5-HT) and 0.9 +/- 0.3 X 10(-6) M (NE), whereas values for the apparent maximal velocity of removal (Vmax) were 17.4 +/- 2.6 X 10(-9) mol/min/g of lung wet weight (5-Ht) and 4.0 +/- 0.9 X 10(-9) mol/min/g of lung wet weight (NE). Furthermore, increasing the dose of administered 5-HT had little effect on NE removal and, similarly, increasing the dose of NE caused only small reductions in 5-HT extraction, indicating distinct sites of removal of these two amines by rabbit pulmonary endothelium.     

Crystal structures,phase transitions,and nuclear magnetic resonance of organic–inorganic hybrid [NH2(CH3)2]2ZnBr4 crystals

Organic–inorganic hybrid [NH₂(CH₃)₂]₂ZnBr₄ crystals were grown via slow evaporation, and their monoclinic structure was determined using single-crystal X-ray diffraction (XRD). The two phase transition temperatures at 401 K (T_C1) and 436 K (T_C2) were defined using differential scanning calorimetry and powder XRD. In the nuclear magnetic resonance spectra, a small change was observed in the ¹H chemical shifts for NH₂, ¹³C chemical shifts for CH₃, and ¹⁴N resonance frequency for NH₂ near T_C1. ¹H spin-lattice relaxation times T_1ρ and ¹³C T_1ρ for NH₂ and CH₃, respectively, rapidly decreased near T_C1, suggesting that energy was easily transferred. NH₂ in the [NH₂(CH₃)₂]⁺ cation was significantly influenced by the surrounding environments of ¹H and ¹⁴N, indicating a change in the N–H⋯Br hydrogen bond with the coordination geometry of the ZnBr₄ anion. These fundamental properties open efficient avenues for the development of organic–inorganic hybrids, thus qualifying them for practical applications.

Thermal ellipsoid plot (50% probability) for the [NH₂(CH₃)₂]₂ ZnBr₄ structure at 300 K.     

Role of metal and anions in organo-metal halide perovskites CH3NH3MX3 (M: Cu,Zn, Ga,Ge, Sn,Pb; X: Cl,Br, I) on structural and optoelectronic properties for photovoltaic applications

Methylammonium metal halide perovskites have recently been explored for new uses due to their unique and exciting optoelectronic properties. Their exceptional electronic properties have often been attributed to the overlap between the metal cation s and halogen p states. In this study, density functional theory calculations have been carried out based on the orthorhombic phase of the organometal trihalide perovskite CH₃NH₃MX₃ (M: Cu, Zn, Ga, Ge, Sn, Pb; X: Cl, Br, I) to systematically investigate the effects of the metal cation and halogen anion on the structural, electronic, and optical properties for solar cell applications. The calculated lattice parameters agree well with previously obtained experimental and theoretical results. All of these perovskites are direct band gap compounds at the G symmetry point, except CH₃NH₃GaX₃. The band gap increases from iodide to chloride and also with the metal cation size, from Ge to Pb or Cu to Zn. Furthermore, metal halide perovskites show blue shifts in their optical absorption spectra with an increase in metal cation size. Among the studied examples, CH₃NH₃GaBr₃ and CH₃NH₃CuCl₃ absorb a wide range of light, from UV to the visible region, and possess very unusual high dielectric constants and refractive indices. Our calculations reveal that CH₃NH₃SnI₃, CH₃NH₃GeI₃, and CH₃NH₃ZnI₃ are favorable candidates for lead-free photovoltaic applications.

Varying the metal and halide in a perovskite can significantly change the resulting properties.     

Anion–cation co-operative catalysis by artificial sweetener saccharine-based ionic liquid for sustainable synthesis of 3,4-dihydropyrano[c]chromenes, 4,5-dihydropyrano[4,3-b]pyran and tetrahydrobenzo[b]pyrans in aqueous medium

In this study, a saccharine-based ionic liquid [Bmim]Sac has been found to be a sustainable catalyst for the synthesis of 3,4-dihydropyrano[c]chromenes, 4,5-dihydropyrano[4,3-b]pyran and tetrahydrobenzo[b]pyrans scaffolds through Domino Knoevenagel–Michael reaction. The easy recovery of the catalyst and high yield of the products make the protocol attractive, sustainable and economical. A mechanistic hypothesis is discussed using the concept of cooperative catalysis based on the dual (electrophilic/nucleophilic) activation of reactants by [Bmim]Sac. Furthermore, dual hydrogen bonding of saccharinate anions plays an important role in the activation of nucleophiles.

Artificial sweetener saccharine based ionic for sustainable synthesis of 3,4-dihydropyrano[c]chromenes, 4,5-dihydropyrano[4,3-b]pyran and tetrahydrobenzo[b]pyrans in aqueous medium scaffolds through Domino Knoevenagel–Michael reaction.     

S33138 [N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1]-benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenylacetamide], a preferential dopamine D3 versus D2 receptor antagonist and potential antipsychotic agent. II. A neurochemical, electrophysiological and behavioral characterization in vivo

The novel benzopyranopyrrolidine, S33138 [N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1]benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenylacetamide], is a preferential antagonist of cloned human D(3) versus D(2L) and D(2S) receptors. In mice, S33138 (0.04-2.5 mg/kg i.p.) increased levels of mRNA encoding c-fos in D(3) receptor-rich Isles of Calleja and nucleus accumbens more potently than in D(2) receptor-rich striatum. Furthermore, chronic (3 weeks) administration of S33138 to rats reduced the number of spontaneously active dopaminergic neurones in the ventral tegmental area (0.16-10.0 p.o.) more potently than in the substantia nigra (10.0). In primates treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, antiparkinson actions of the D(3)/D(2) agonist, ropinirole, were potentiated by low doses of S33138 (0.01-0.16 p.o.) but diminished by a high dose (2.5). Consistent with antagonism of postsynaptic D(3)/D(2) sites, S33138 attenuated hypothermia and yawns elicited by the D(3)/D(2) agonist 7-OH-DPAT [(+)-7-dihydroxy-2-(di-n-propylamino)-tetralin] in rats, and it blocked (0.01-0.63, s.c.) discriminative properties of PD128,907 [(+)-(4aR,10bR)-3,4, 4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol; trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolininecarboxamide]. Suggesting antagonist properties at D(3)/D(2) autoreceptors, S33138 prevented (0.16-2.5 s.c.) the inhibitory influence of PD128,907 upon dopamine release in frontal cortex, nucleus accumbens, and striatum and abolished (0.004-0.25 i.v.) its inhibition of ventral tegmental dopaminergic neuron firing. At higher doses, antagonist actions of S33138 (0.5-4.0 i.v.) at alpha(2C)-adrenoceptors were revealed by an increased firing rate of adrenergic perikarya. Finally, antagonism of 5-hydroxytryptamine (5-HT(2A) and 5-HT(7)) receptors was shown by blockade of 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane-induced head twitches (0.63-10.0 s.c.) and 5-carboxytryptamine-induced hypothermia (2.5-20.0 i.p.), respectively. In conclusion, S33138 displays modest antagonist properties at central alpha(2C)-adrenoceptors, 5-HT(2A) and 5-HT(7) receptors. Furthermore, in line with its in vitro actions, it more potently blocks cerebral populations of D(3) versus D(2) receptors.     

Assessment of insulin action in insulin-dependent diabetes mellitus using [6(14)C]glucose, [3(3)H]glucose, and [2(3)H]glucose. Differences in the apparent pattern of insulin resistance depending on the isotope used.

To determine whether [2(3)H], [3(3)H], and [6(14)C]glucose provide an equivalent assessment of glucose turnover in insulin-dependent diabetes mellitus (IDDM) and nondiabetic man, glucose utilization rates were measured using a simultaneous infusion of these isotopes before and during hyperinsulinemic euglycemic clamps. In the nondiabetic subjects, glucose turnover rates determined with [6(14)C]glucose during insulin infusion were lower (P less than 0.02) than those determined with [2(3)H]glucose and higher (P less than 0.01) than those determined with [3(3)H]glucose. In IDDM, glucose turnover rates measured with [6(14)C]glucose during insulin infusion were lower (P less than 0.05) than those determined with [2(3)H]glucose, but were not different from those determined with [3(3)H]glucose. All three isotopes indicated the presence of insulin resistance. However, using [3(3)H]glucose led to the erroneous conclusion that glucose utilization was not significantly decreased at high insulin concentrations in the diabetic patients. [6(14)C] and [3(3)H]glucose but not [2(3)H]glucose indicated impairment in insulin-induced suppression of glucose production. These results indicate that tritiated isotopes do not necessarily equally reflect the pattern of glucose metabolism in diabetic and nondiabetic man.     

Diastereoselective synthesis of CF3-dihydrobenzofurans by [4+1] annulation of in situ-generated CF3-o-quinone methides and sulfur ylides

An efficient and highly diastereoselective synthesis of CF₃-dihydrobenzofurans by the reaction of in situ-generated CF₃-oQMs in the presence of a base with sulphur ylides is put forward. The generality of the present developed method was well studied with diverse substrates to access the corresponding products in excellent yields. The highly reactive CF₃-oQM has been utilized first time for the annulation reaction.

The first [4 + 1] annulation reaction of in situ-generated highly electrophilic CF₃-ortho-quinone methides with sulphur ylides has been put forth under mild reaction conditions to access CF₃-dihydrobenzofurans.

Fluorine or fluoroalkyl group-containing organic molecules occupy a vital position in drug discovery due to the unique impact of fluorine atom in terms of lipophilicity, permeability, and protein-binding.¹ In the last two years, 45% of FDA-approved small molecule pharmaceuticals are fluorinated, which denotes the importance of synthesizing fluorinated molecules, with special emphasis on medicinal chemistry, for the identification of new scaffolds. Among the fluorinated functional groups, the trifluoromethyl group has emerged as one of the imperative fluoroalkyl groups to enhance the bio-efficacy and metabolic stability of the corresponding motifs, which is needed for the identification of lead compounds.² Thus, finding new methods for the inclusion of the CF₃ group into novel biological entities is always desirable and challenging.In this context, ortho-quinone methides (oQMs) are powerful reactive intermediates in synthetic organic chemistry to construct complex medium sized rings.^3,4 Since oQM was first observed in 1907, it created a large impact in the synthesis of oxygen-containing benzannulated rings, which are of interest as photochromic materials and biologically active compounds.³ However, the reactions of oQMs were restricted to electron-rich substrates due to their high electrophilic nature. However, annulation reactions of diversely substituted oQMs (substitution on the exocyclic double bond) were explored extensively for the construction of oxygen-containing complex heterocyclic structures;³ however, it is quite surprising that annulation reactions involving trifluoromethyl-substituted oQM (CF₃-oQM) have not been reported yet, especially because CF₃-oQM is like a gold mine and could open the realm to construct versatile fluorinated oxygen architectures.Kato et al. were the first to report the nucleophilic addition of Grignard reagents and amines to the in situ-generated trifluoromethyl-substituted ortho- and para-quinone methides (Fig. 1a).⁵ After that, there were no reports of this in situ-generated CF₃-oQM for any nucleophilic additions and annulations. In 2020, several papers were published on in situ-generated CF₃-para-quinone methides (CF₃-pQM) by quickly trapping them with different carbon and hetero atom-centered nucleophiles (Fig. 1b).⁶ Notably, Waser et al. demonstrated that CF₃-pQM has higher electrophilicity parameter (E) when compared to other substituted para-quinone methides.^6d Similarly, we hypothesized that CF₃-oQMs may also have higher “E” in comparison with the corresponding oQMs. Thus, the utilization of this highly reactive CF₃-oQM for annulation reactions is extremely challenging and equally desirable towards the synthesis of novel organofluorine molecules. In continuation of our research interest on oQM-based annulations and the development of new fluorinating methodologies,⁷ herein, we report for the first [4 + 1] annulation of in situ-generated CF₃-oQM with sulphur ylide to access trifluoromethyl-substituted dihydrobenzofurans with high diastereoselectivity.Open in a separate windowFig. 1Previous work vs. the present work.The study was initiated by exposing 2-(1-chloro-2,2,2-trifluoroethyl) phenol 1a and sulphur ylide 2a to 1.2 equiv. of Cs₂CO₃ at room temperature in THF. Delightedly, the in situ-generated CF₃-oQM was successfully trapped with sulphur ylide to afford the corresponding trifluoromethyl-substituted dihydrobenzofuran 3a in 80% yield (

Role of NH4 ions in successive phase transitions of perovskite type (NH4)2ZnX4 (X = Cl,Br) by 1H MAS NMR and 14N NMR

The ¹H chemical shifts and the spin-lattice relaxation time, T_1ρ, in the rotating frame of (NH₄)₂ZnX₄ (X = Cl, Br) are observed in order to investigate local phenomena related to successive phase transitions. The temperature dependence of T_1ρ values for ¹H showed a minimum, and the T_1ρ values for ¹H appeared to be governed by tumbling molecular motions at high temperatures. In addition, ¹⁴N NMR spectra are studied in each phase of (NH₄)₂ZnX₄ single crystals in the laboratory frame. The phase transition temperatures strongly affect the ¹⁴N number of symmetry related nitrogen centers within the unit cell. The ¹H MAS NMR and ¹⁴N NMR results are discussed to elucidate the roles of NH₄ ions during the phase transitions of (NH₄)₂ZnX₄.

The ¹H chemical shifts and the spin-lattice relaxation time, T_1ρ, in the rotating frame of (NH₄)₂ZnX₄ (X = Cl, Br) are observed in order to investigate local phenomena related to successive phase transitions.     

Identification of distinct C3b and C4b recognition sites in the human C3b/C4b receptor (CR1, CD35) by deletion mutagenesis

Complementary DNA clones encoding the NH2-terminal region of human CR1 have been isolated and sequenced. The deduced complete amino acid sequence of the F allotype of human CR1 contains 2,039 residues, including a 41-residue signal peptide, an extracellular domain of 1,930 residues, a 25-amino acid transmembrane domain, and a 43-amino acid cytoplasmic region. The extracellular domain is composed exclusively of 30 short consensus repeats (SCRs), characteristic of the family of C3/C4-binding proteins. The 28 NH2-terminal SCRs are organized as four long homologous repeats (LHRs) of seven SCRs each. The newly sequenced LHR, LHR-A, is 61% identical to LHR-B in the NH2-terminal two SCRs and greater than 99% identical in the COOH-terminal five SCRs. Eight cDNA clones were spliced to form a single construct, piABCD, that contained the entire CR1 coding sequence downstream of a cytomegalovirus promoter. COS cells transfected with piABCD transiently expressed recombinant CR1 that comigrated with the F allotype of erythrocyte CR1 on SDS-PAGE and that mediated rosette formation with sheep erythrocytes bearing C4b and C3b. Recombinant CR1 also had factor I-cofactor activity for cleavage of C3(ma). Analyses of six deletion mutants expressed in COS cells indicated that the NH2-terminal two SCRs of LHR-A contained a site determining C4 specificity and the NH2-terminal two SCRs of LHR-B and -C each had a site determining C3 specificity. The presence of these three distinct sites in CR1 may enable the receptor to interact multivalently with C4b/C3b and C3b/C3b complexes generated during activation of the classical and alternative pathways.     

Differences in Transport Mechanisms of trans-1-Amino-3-[18F]Fluorocyclobutanecarboxylic Acid in Inflammation,Prostate Cancer,and Glioma Cells: Comparison with l-[Methyl-11C]Methionine and 2-Deoxy-2-[18F]Fluoro-d-Glucose

Purpose

We aimed to elucidate trans-1-amino-3-[¹⁸F]fluorocyclobutanecarboxylic acid (anti-[¹⁸F]FACBC) uptake mechanisms in inflammatory and tumor cells, in comparison with those of l-[methyl-¹¹C]methionine ([¹¹C]Met) and 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG).

Procedures

Using carbon-14-labeled tracers, in vitro time-course, pH dependence, and competitive inhibition uptake experiments were performed in rat inflammatory (T cells, B cells, granulocytes, macrophages), prostate cancer (MLLB2), and glioma (C6) cells.

Results

Anti-[¹⁴C]FACBC uptake ratios of T/B cells to tumor cells were comparable, while those of granulocytes/macrophages to tumor cells were lower than those for [¹⁴C]FDG. Over half of anti-[¹⁴C]FACBC uptake by T/B and tumor cells was mediated by Na⁺-dependent amino acid transporters (system ASC), whereas most [¹⁴C]Met transport in all cells was mediated by Na⁺-independent carriers (system L).

Conclusions

The low anti-[¹⁸F]FACBC accumulation in granulocytes/macrophages may be advantageous in discriminating inflamed regions from tumors. The significant anti-[¹⁸F]FACBC uptake in T/B cells may cause false-positives in some cancer patients who undergo FACBC-positron emission tomography (PET).