Ester-armed cyclens having quadruplicated helical geometry: remarkably stable and selective encapsulation of Na+ ion

A new series of ester-armed cyclens nicely accommodated a Na+ ion in their quadruplicated helical binding spheres and effectively discriminated the cation from Li+ and K+ ions. Crystallographic studies revealed that four ester-functionalized sidearms provided effective coordination with the Na+ ion trapped in the 12-membered cyclen ring. Log K values for their Na+ complexes were estimated as 9-11 in CD3CN or C2D5OD, which were comparable to those of common bicyclic cryptands. FAB-MS, liquid-liquid extraction, and NMR binding experiments demonstrated that the cooperative action of the parent cyclen ring and ester-functionalized sidearms offered stable and selective encapsulation of the Na+ ion based on unique quadruplicated helical geometry.     

A joint experimental and theoretical study of cation-pi interactions: multiple-decker sandwich complexes of ferrocene with alkali metal ions (Li+, Na+, K+, Rb+, Cs+)

A systematic study of cation-pi interactions between alkali metal ions and the cyclopentadienyl ring of ferrocene is presented. The alkali metal (Li+, Na+, K+, Rb+, Cs+) salts of the ditopic mono(pyrazol-1-yl)borate ligand [1,1'-fc(BMe2pz)2]2- crystallize from dimethoxyethane as multiple-decker sandwich complexes with the M+ ions bound to the pi faces of the ferrocene cyclopentadienyl rings in an eta5 manner (fc = (C5H4)2Fe; pz = pyrazolyl). X-ray crystallography of the lithium complex reveals discrete trimetallic entities with each lithium ion being coordinated by only one cyclopentadienyl ring. The sodium salt forms polyanionic zigzag chains where each Na+ ion bridges the cyclopentadienyl rings of two ferrocene moieties. Linear columns [-CpR-Fe-CpR-M+-CpR-Fe-CpR-M+-](infinity) (R = [-BMe2pz]-) are established by the K+, Rb+, and Cs+ derivatives in the solid state. According to DFT calculations, the binding enthalpies of M+-eta5(ferrocene) model complexes are about 20% higher as compared to the corresponding M+-eta6(benzene) aggregates when M+ = Li+ or Na+. For K+ and Rb+, the degree of cation-pi interaction with both aromatics is about the same. The binding sequence along the M+-eta5(ferrocene) series follows a classical electrostatic trend with the smaller ions being more tightly bound.     

The cyclooctatriene-eta2-ynyl potassium zwitterionic radical: evidence for a potassium organometallic

Low-temperature (-120 degrees C) dehydrohalogenation of bromocyclooctatetraene (BrC8H7) with either sodium or potassium tert-butoxide followed by alkali metal reduction was used to generate the anion radical of [8]annulyne (C8H6*-) in tetrahydrofuran. EPR analysis at -120 degrees C reveals an extraordinarily large metal splitting when K or Cs (aK of 0.214 G and aCs of 3.26 G) serves as the reducing agent. The large aM is due to the metal cation interacting with the p-orbitals, within the alkyne moiety, that are in the plane of the ring system. The ionic radius of K+ is 1.33 A, which is larger than the B3LYP predicted distance between carbons 1 and 2 (1.23 A). However, the ionic radius of Na+ is only 0.95 A, and it is too small to simultaneously interact with both p-orbitals. Hence, no aM is observed when Na (ordinarily aNa > aK) or Li serves as the reducing agent. After the addition of 18-crown-6 to either the K or the Cs reduced system, two anion radicals are present. One is the system where the 18-crown-6 encapsulated metal complex is normally ion paired over the face of the ring system and aM = 0. The other is the cyclooctatriene-eta2-ynyl 18-crown-6 encapsulated metal zwitterion radical exhibiting a large aM. The ion pair to organometallic equilibrium constant is 1.6 +/- 0.1 and 3.5 +/- 0.1 for the K and Cs systems, respectively.     

冠醚配合物的热力学性质的研究 III. 碱金属离子与18C6甲基衍生物配位反应的电导研究

The coordination reaction of Na+, K+, Rb+ and Cs+ with benzo- 15-crown-5, 18-crown-6 and the newly synthesized cyclic polyethers 2, 3-benzo-8, 15-dimethyl-18-crown-6, 2, 3-benzo-8, 11, 15-trimethyl-18-crown-6 in methanol at 25`C has been studied by conductometric titration. The stability constants for the 1:1 coordination compounds were calculated. The marked selectivity of 18-crown-6 toward alkali metal ions was not found in its methyl derivatives. The induction effect of the benzene ring and methyl group on polyether ring reduced the stability of the coordination compounds. In methanol, the stability sequence of te compounds of alkali metal ions with 18-crown-6 was K+>Rb+>Cs+>Na+, that of its dimethyl derivative was K+>Rb+>Na+>Cs+ and that of its trimethyl derivative was K+>Na+>Rb+>Cs+, that is, the methyl substituent had a weaker influence on the stability of Na+ compound than on that of Rb+ or Cs+ compound. In the range of concentration studied, decrease in equivalent conductance is in agreement with the prediction on the basis of the structure of the complexes. The above results may give a clue for modifying the structure of a crown ether for specified selectivity.     

冠醚配合物热力学性质的研究 X: 用NMR研究15-冠-5-衍生物与钠离子的配位反应

用^2^3Na NMR研究了15-冠-5(15C5), 2,3-苯并-15-冠-5(B-15C5), 2,3-苯并-6-甲基-15-冠-5(BCl-15C5), 2,3-苯并-8,12-二甲基-15-冠-5(BC2-15C5)在丙酮中与Na^+的配位反应, 由此探索甲基的影响, 实验结果表明, 当在金属盐溶液中加入冠醚, 配体为15C5时, 体系表观化学位移移至低场, 配体为B-15C5, BC1-15C5, BC2-15C5时, 体系在表观化学位移移至高场, 后者与苯并-18-冠-6及其甲基衍生物不同, 这是由于苯环在空间排布不同所致, 用Newton-Raphson法和描坑法(Pit-mapping)拟合实验数据, 发现BC1-15C5和BC2-15C5除形成NaL^+和NaL2^+外还有不稳定的Na3L2^3^+形成。本文对形成过程和生成NaL^+反应的平衡常数lgK11与甲基数的关系亦作了讨论, lgK11与甲基数目n近似成直线关系, 可用下式表示: lgK11=3.50-0.80n, n=0,1,2。     

Cyclohexane as a Li+ selective ionophore

The M+[cyclohexane][Ar] (M = Li, Na, and K) cluster ions were investigated using infrared photodissociation spectroscopy in the C-H stretching region. The alkali metal cation binds to the cyclohexane ring above the ring on the S6 axis via eta3 coordination. The C-H stretching modes are perturbed due to binding of the metal cation and display a significant spread in frequency. The shifts are greatest for the Li+ and decrease for Na+ and K+ with increasing ionic radius. It has been observed that cyclohexane displays greater selectivity for Li+ over Na+ than the cyclic ether, 12-crown-4. The charge transfer interaction between Li+ and cyclohexane is believed to be responsible for the selectivity of Li+ over other alkali metal ions.     

A PGSE diffusion and electrophoretic NMR study of Cs+ and Na+ dynamics in aqueous crown ether systems

Multinuclear pulsed gradient spin-echo (PGSE) NMR diffusion and linewidth measurements were used to probe binding and transport in aqueous Na+-15-crown-5, Na+-18-crown-6, Cs+-15-crown-5 and Cs+-18-crown-6 systems. Since direct PGSE observation of many alkali cations is precluded by either low inherent sensitivity or rapid relaxation (or both), the feasibility of proton-detected electrophoretic NMR (ENMR) measurements to complement PGSE data was investigated. ENMR measurements were performed on aqueous Cs+-, Li+-, Na+-, K+-, and Rb+- 18-crown-6 systems. The data analysis is based on a two-site binding model and its corresponding association constants. Cs+ was found to bind considerably more tightly to 18-crown-6 (K=8 M-1) than to 15-crown-5 (K approximately 2 M-1), whereas Na+ had almost equal affinity (K approximately 4.5 M-1) for 15-crown-5 and 18-crown-6. The difficulties encountered in analysing the NMR parameters, methodological limitations and the implied need for more complicated binding models are discussed.     

Potassium-selective membrane electrodes based on macrocyclic metacyclophanes analogous to calixarenes.

The tetrabutyl ester derived from 9,16,25,32-tetrahydroxy[3.1.3.1]metacyclophane was an excellent ionophore for constructing a K+-selective membrane electrode. This ionophore exhibited a much higher selectivity toward K+ than the structurally similar potassium ionophore IV commercially available from Fluka. In particular, the interference from organic ammonium ions decreased remarkably. Potassium ionophore IV possessed oxygen atoms in the ring structure, while the present ionophore changed the oxygen atoms to carbon atoms. Thus, the removal of oxygen atoms in ring constituents of the metacyclophane acted to reduce the interaction with the NH3+ group of organic ammonium ions. The size of the cavity of the present ionophore was between those of calix[4]arene and calix[6]arene derivatives, which act as Na+ and Cs+ ionophores, respectively, demonstrating that the ability to recognize alkali metal cations was strongly cavity size-dependent. The present K+-selective electrode had less interference from Rb+ and Cs+ than an electrode constructed using valinomycin, but suffered greater interference from Na+.     

Ion-specific swelling of poly(styrene sulfonic acid) hydrogel

Poly(styrene sulfonic acid) (PSSA) hydrogel was prepared by radiation crosslinking using methyl N,N-bis-acrylamide as crosslinker. Effects of ion species and concentration on the swelling behavior of PSSA hydrogel were investigated in aqueous solution of selected anions (F-, Cl-, Br-, SCN-), cations (Li+, Na+, K+, Ca2+), and hydrophobic ions (tetramethylammonium cation TMA+, tetrabutylammonium cation TBA+, and dodecyltrimethylammonium cation TAB+). The deswelling extent of PSSA hydrogel follows anion Hofmeister series, i.e., SCN- < Br- < Cl- < F-, in solutions containing selected anions and K+ as counterion up to a concentration of 2 mol.L(-1). On the contrary, the deswelling extent of PSSA hydrogel in solutions containing selected cations and Cl- follows the sequence of Li+ < Na+ < K+ < Ca2+, which is the reverse of the Hofmeister series except Ca2+. We have discussed the effects of ions on the hydrogen bonding through SO3- and phenyl ring in salt solutions at low and high concentrations. Other interactions, such as the cation-pi and hydrophobic interactions, also contributed to the ion-specific swelling of PSSA hydrogel. The proposed mechanism was further elucidated by FTIR and NMR analysis. A very specific deswelling-reswelling phenomenon of PSSA hydrogel in KF solution has been observed and ascribed to the F- binding to phenyl ring through a specific interaction.     

Diazacoronand linked beta-cyclodextrin dimer complexes of Brilliant Yellow tetraanion and their sodium(I) analogues

Complexation of the Brilliant Yellow tetraanion, 3(4-), by two new diazacoronand linked beta-cyclodextrin (beta CD) dimers 4,13-bis(2-(6A-deoxy-beta-cyclodextrin-6A-yl)aminooctylamidomethyl- and 4,13-bis(8-(6A-deoxy-beta-cyclodextrin-6A-yl)aminooctylamidomethyl)-4,13- diaza-1,7,10-trioxacyclopentadecane, 1 and 2, respectively, has been studied in aqueous solution. UV-visible spectrophotometric studies at 298.2 K, pH 10.0 and I = 0.10 mol dm-3 (NEt4ClO4) yielded complexation constants for the complexes 1 x 3(4-) and 2 x 3(4-), K1 = (1.08 +/- 0.01) x 10(5) and (6.21 +/- 0.08) x 10(3) dm3 mol-1, respectively. Similar studies at 298.2 K, pH 10.0 and I = 0.10 mol dm-3 (NaClO4) yielded K3 = (4.63 +/- 0.09) x 10(5) and (3.38 +/- 0.05) x 10(4) dm3 mol-1 for the complexation of 3(4-) by Na+ x 1 and Na+ x 2 to give Na+ x 1 x 3(4-) and Na+ x 2 x 3(4-), respectively. Potentiometric studies of the complexation of Na+ by 1 and 2 by the diazacoronand component of the linkers to give Na+ x 1 and Na+ x 2 yielded K2 = (2.00 +/- 0.05) x 10(3) and (1.8 +/- 0.05) x 10(3) dm3 mol-1, respectively, at 298.2 K and I = 0.10 mol dm-3(NEt4ClO4). For complexation of Na+ by 1 x 3(4-) and 2 x 3(4-) to give Na+ x 1 x 3(4-) and Na+ x 2 x 3(4-) K2K3/K1 = K4 = 8.6 x 10(2) and 9.8 x 10(3) dm3 mol-1, respectively. The pKaS of 1H4(4+) are 7.63 +/- 0.01, 6.84 +/- 0.02, 5.51 +/- 0.04 and 4.98 +/- 0.03, and those of 2H4(4+) are 8.67 +/- 0.02, 8.11 +/- 0.02, 6.06 +/- 0.02 and 5.14 +/- 0.05. The larger magnitude of K1 for 1 by comparison with K1 for 2 is attributed to the octamethylene linkers of 2 competing with 3(4-) for occupancy of the annuli of the beta CD entities while the competitive ability of the dimethylene linkers of 1 is less. A similar argument applies to the relative magnitudes of K3 for Na+ x 1 and Na+ x 2. Increased electrostatic attraction probably accounts for K3 > K1 for Na+ x 1 x 3(4-) and 1 x 3(4-) and for Na+ x 2 x 3(4-) and 2 x 3(4-). The lesser magnitudes of K2 and K4 for Na+ x 1 and Na+ x 1 x 3(4-) compared with those for Na+ x 2 and Na+ x 2 x 3(4-) are attributed to the octamethylene linkers of 2 producing a more hydrophobic environment for the diazacoronand than that produced by the dimethylene linkers of 1. 1H NMR spectroscopic studies and the syntheses of 1 and 2 are described.     

Mechanism of a novel exchange process in alkali metal salts of 1,5-dicyclooctatetraenylnaphthalene dianion

A novel low-temperature intramolecular exchange was detected by (13)C NMR spectrometry in the Na(+) and K(+) salts of the title compound. The process causes the pairwise exchange in the dianion ring of C(2"), C(3"), and C(4") with C(8"), C(7"), and C(6"), respectively. The free energy of activation (DeltaG()(exch)) for the dipotassium salt (2(2-)/2K(+)) in THF-d(8) at 230 K is 12.6 kcal mol(-1). Two key questions are addressed: (1) Why are these carbons anisochronous and (2) what is the mechanism of exchange? NMR data for 1-cyclooctatetraenylnaphthalenedipotassium (3(2-)/2K(+)) as well as ab initio HF/3-21G(++) calculations for 3, 3(2-), and 3(2-)/2K(+) indicate that the nonequivalence is due to both slow rotation across a barrier at which the naphthalene and COT(2)(-) rings are approximately coplanar and slow inversion of the neutral COT ring. This results in the noteworthy circumstance of diastereotopic carbons being observed in a molecule that does not possess either a stereogenic or a prostereogenic center. Comparison of DeltaG()(exch) and DeltaG(++)(BS) for 2(2-)/2K(+) with the corresponding values for 2(2-)/2Na(+) and 2(2-)/2Li(+) and of DeltaG(++)(exch) with DeltaG(++) for ring inversion in 1,4-dicyclooctatetraenylnaphthalene leads to the conclusion that COT(2-) ring rotation and COT ring inversion both contribute to exchange in 2(2-)/2K(+) in a 3:1 ratio, but that exchange occurs exclusively by ring rotation in 2(2-)/2Li(+). The latter result is attributed to looser ion pairing in the dilithium (and disodium) salts.     

Cellular cation transport studied by 6/7Li and 23Na NMR in a porous Mo132 Keplerate type nano-capsule as model system

Li+ ions can interplay with other cations intrinsically present in the intra- and extra-cellular space (i.e. Na+, K+, Mg2+ and Ca2+) have therapeutic effects (e.g. in the treatment of bipolar disorder) or toxic effects (at higher doses), likely because Li+ interferes with the intra-/extra-cellular concentration gradients of the mentioned physiologically relevant cations. The cellular transmembrane transport can be modelled by molybdenum-oxide-based Keplerates, i.e. nano-sized porous capsules containing 132 Mo centres, monitored through 6/7Li as well as 23Na NMR spectroscopy. The effects on the transport of Li+ cations through the 'ion channels' of these model cells, caused by variations in water amount, temperature, and by the addition of organic cationic 'plugs' and the shift reagent [Dy(PPP)2](7-) are reported. In the investigated solvent systems, water acts as a transport mediator for Li+. Likewise, the counter-transport (Li+/Na+, Li+/K+, Li+/Cs+ and Li+/Ca2+) has been investigated by 7Li NMR and, in the case of Li+/Na+ exchange, by 23Na NMR, and it has been shown that most (in the case of Na+ and K+, all (Ca2+) or almost none (Cs+) of the Li cations is extruded from the internal sites of the artificial cell to the extra-cellular medium, while Na+, K+ and Ca2+ are partially incorporated.     

刺五加寡糖的电喷雾多级串联质谱研究

采用小柱层析法从刺五加中分离得到刺五加寡糖类系列化合物(刺五加二糖刺五加六糖).实验结果表明,在正离子模式下的ESI-MS谱中,此类化合物呈现出特征的加合离子峰簇[M+Na]⁺/[M+K]⁺或[M+H₂O+Na]⁺/[M+H₂O+K]⁺,可以确定其分子量;在负离子模式下的ESI-MS谱中,刺五加寡糖易形成[M-H]^-/[M+nH₂O-H]^-(n<3).还利用电喷雾多级串联质谱(ESI-MSⁿ)对刺五加三糖进行了系统的研究,推断出刺五加三糖的组成与结构.     

Experimental and theoretical study of the vibrational spectra of 12-crown-4-alkali metal cation complexes

The vibrational, Raman, and IR, spectra of the five 12-crown-4 (12c4) complexes with Li+, Na+, K+, Rb+, and Cs+ alkali metal cations were measured. Except for a small shift of the position of some bands in the vibrational spectra of the Li+ complex, the vibrational spectra of the five complexes are so similar that it is concluded that the five complexes exist in the same conformation. B3LYP/6-31+G* force fields were calculated for six of the eight predicted conformations in a previous report (J. Phys. Chem. A 2005, 109, 8041) of the 12c4-Li+, Na+, and K+ complexes that are of symmetries higher than the C1 symmetry. These six conformations, in energy order, are of C4, Cs, Cs, C(2v), C(2v), and Cs symmetries. Comparison between the experimental and calculated vibrational frequencies assuming any of the above-mentioned six conformations shows that the five complexes exist in the C4 conformation. This agrees with the fact that the five alkali metal cations are larger than the 12c4 ring cavity. The B3LYP/6-31+G* force fields of the C4 conformation of the Li+, Na+ and K+ complexes were scaled using a set of eight scale factors and the scale factors were varied so as to minimize the difference between the calculated and experimental vibrational frequencies. The root-mean-square (rms) deviations of the calculated frequencies from the experimental frequencies were 7.7, 5.6, and 5.1 cm(-1) for the Li+, Na+, and K+ complexes, respectively. To account for the earlier results of the Li+ complex that the Cs conformation is more stable than the C4 conformation by 0.16 kcal/mol at the MP2/6-31+G* level, optimized geometries of the complex were calculated for the C4 and Cs conformations at the MP2/6-311++G** level. The C4 conformation was calculated to be more stable than the Cs conformation by 0.13 kcal/mol.     

脂双层膜上双冠醚对碱金属离子的选择性

1967年,C.J.Pederson合成了一系列大环多醚及其与碱金属离子形成的稳定配合物,其后,G.Eisenman等研究了由许多类脂物质所构成的人工双层膜上的渗透性和电导,指出大环化合物能促进碱金属阳离子的运送选择性,本工作用5种Schiff碱型双冠醚作为离子载体修饰脂双层膜,研究了它们对碱金属离子的选择性。     

Decationization and dealumination of clinoptilolite tuff and ammonium exchange on acid-modified tuff

The paper presents results of investigation of exchange of the clinoptilolite tuff cations with hydrogen ions from HCl solution of concentration 0.1 mmol cm(-3) and ammonium ions solutions of concentrations 0.0071 to 2.6 mmol cm(-3). Molal concentrations, x (mmol g(-1)) of cations exchanged in acid solution and in ammonium ions solutions were compared with molal concentrations of cations obtained by determination of the cation-exchange capacity of clinoptilolite tuff. The obtained results show that at ammonium ion concentrations lower than 0.1 mmol cm(-3), with regard to exchange capacity for particular ions, best exchanged are Na+ ions, followed by Mg2+ and Ca2+ ions, while exchange of K+ ions is the poorest (Na+ > Mg2+ > Ca2+ > K+). At ammonium concentrations from 0.2 to 1 mmol cm(-3) the order is Na+ > Ca2+ > Mg2+ > K+. At concentrations higher than 1 mmol cm(-3) the order is Na+ > Ca2+ > K+ > Mg2+. The results are a consequence of the uptake of hydrogen ions by zeolite samples in ammonium ions solutions at concentrations lower than 1 mmol cm(-3) and indicate the importance of Mg2+ (besides Na+ ions) for the exchange between clinoptilolite cations and H+ ions, in contrast to K+ ions, whose participation in the reaction with H+ ions is the lowest. During decationization of the clinoptilolite in acid solution, best exchanged are Na+, Mg2+, and Ca2+ ions, while exchange of K+ ions is the poorest. Due to poor exchange of K+ and H+ ions and good exchange of Na+, Mg2+, and Ca2+ ions, it is to be assumed that preservation of stability of the clinoptilolite structure is caused by K+ ions present in the channel C. Clinoptilolite is dissolved in the clinoptilolite A and B channels where Na+, Mg2+, and Ca2+ ions are present. On the acid-modified clinoptilolite samples, exchange of ammonium ions is poorer than on natural zeolite. The longer the contact time of the zeolite and acid solution, the worse ammonium ions exchange. It can be assumed that H+ ions exchanged with zeolite cations are consumed for solution of aluminum in the clinoptilolite structure; therefore the concentration of H+ ions as exchangeable cations decreases. In the ammonium ion solution at a concentration of 0.0065 mmol cm(-3), from the acid-modified zeolite samples, Al3+ ions are exchanged best, followed by Na+, Mg2+, Ca2+, and K+ ions. Further to the results, it is to be assumed that exchangeable Al3+ ions available from clinoptilolite dissolution are best exchanged with H+ ions in acid solution.     

Magnetic resonance and kinetic studies of the mechanism of membrane-bound sodium and potassium ion- activated adenosine triphosphatase.

EPR and water proton relaxation rate (1/T1) studies of partially (40%) and "fully" (90%) purified preparations of membrane-bound (Na+ + K+) activated ATPase from sheep kidney indicate one tight binding site for Mn2+ per enzyme dimer, with a dissociation constant (KD = 0.88 muM) in agreement with the kinetically determined activator constant, identifying this Mn2+-binding site as the active site of the ATPase. Competition studies indicate that Mg2+ binds at this site with a dissociation constant of 1 mM in agreement with its activator constant. Inorganic phosphate and methylphosphonate bind to the enzyme-Mn2+ complex with similar high affinities and decrease 1/T1 of water protons due to a decrease from four to three in the number of rapidly exchanging water protons in the coordination sphere of enzyme-bound Mn2+. The relative effectiveness of Na+ and K+ in facilitating ternary complex formation with HPO2-4 and CH3PO2-3 as a function of pH indicates that Na+ induces the phosphate monoanion to interact with enzyme-bound Mn2+. Thus protonation of an enzyme-bound phosphoryl group would convert a K+-binding site to a Na+-binding site. Dissociation constants for K+ and Na+, estimated from NMR titrations, agreed with kinetically determined activator constants of these ions consistent with binding to the active site. Parallel 32Pi-binding studies show negligible formation (less than 7%) of a covalent E-P complex under these conditions, indicating that the NMR method has detected an additional noncovalent intermediate in ion transport. Ouabain, which increases the extent of phosphorylation of the enzyme to 24% at pH 7.8 and to 106% at pH 6.1, produced further decreases in 1/T1 of water protons. Preliminary 31P- relaxation studies of CH3PO2-3 in the presence of ATPase and Mn2+ yield an Mn to P distance (6.9 +/- 0.5 A) suggesting a second sphere enzyme-Mn-ligand-CH3PO2-3 complex. Previous kinetic studies have shown that T1+ substitutes for K+ in the activation of the enzyme but competes with Na+ at higher levels. From the paramagnetic effect of Mn2+ at the active site on the enzyme on I/T1 of 205T1 bound at the Na+ site, a Mn2+ to T1+ distance of 4.0 +/- 0.1 A is calculated, suggesting the sharing of a common ligand atomy by Mn2+ and T1+ on the ATPase. Addition of Pi increases this distance to 5.4 A consistent with the insertion of P between Mn2+ and T1+. These results are consistent with a mechanism for the (Na+ + K+)-ATPase and for ion transport in which the ionization state of Pi at a single enzyme active site controls the binding and transport of Na+ and K+, and indicate that the transport site for monovalent cations is very near the catalytic site of the ATPase. Our mechanism also accounts for the order of magnitude weaker binding of Na+ compared to K+.     

Synthesis and biological activity of N-(aminoiminomethyl)-1H-indole carboxamide derivatives as Na+/H+ exchanger inhibitors

A series of N-(aminoiminomethyl)-1H-indole carboxamide derivatives were synthesized and their inhibitory potencies against the Na+/H+ exchanger were measured. Variation of the carbonylguanidine group at the 2- to 7-position of the indole ring system showed that a substitution at the 2-position improved the Na+/H+ exchanger inhibitory activity the most in vitro. This led to the synthesis and evaluation of an extensive series of N-(aminoiminomethyl)-1H-indole-2-carboxamide derivatives. Derivatives having an alkyl or substituted alkyl group at the 1-position of the indole ring system showed higher levels of in vitro activities. N-(aminoiminomethyl)- 1-(2-phenylethyl)-1H-indole-2-carboxamide (49) had the strongest activity.     

Mass spectral evidence of alkali metal insertion into C60-cyclooctatetraene complexes: M+@C60-C8H 8 *3-

C60 can be reduced to its trianion anion radical in hexamethylphosphoramide with potassium or cesium metal. The addition of water to these solutions, followed by toluene extraction, yields materials that exhibit the expected mass spectral peaks for the Birch reduction products of C 60 *3- (C60Hn). However, when cyclooctatetraene (COT) is present in the solution, the mass spectral signature for the Birch reduction products of M+@C60-COT*3- and C60-COT*3- are also found. The trianion radical of C60 reacts with COT in HMPA to yield a [2 + 2] cycloaddition product, and subsequent ring opening provides a passageway for the Cs+ or K+ counterion to the interior of the fullerene. Analogous results are not observed when the smaller metals (Na and Li) are used as the reducing agents. Only the larger alkali metal cations form tight ion pairs with the trianion of C60-COT. The tight ion association is necessary to bring the cation into a sufficiently close proximity to the trianion for the cation to proceed to the interior.     

The special five-membered ring of proline: An experimental and theoretical investigation of alkali metal cation interactions with proline and its four- and six-membered ring analogues

The interaction of the alkali metal cations, Li+, Na+, and K+, with the amino acid proline (Pro) and its four- and six-membered ring analogues, azetidine-2-carboxylic acid (Aze) and pipecolic acid (Pip), are examined in detail. Experimentally, threshold collision-induced dissociation of the M+(L) complexes, where M = Li, Na, and K and L = Pro, Aze, and Pip, with Xe are studied using a guided ion beam tandem mass spectrometer. From analysis of the kinetic energy dependent cross sections, M(+)-L bond dissociation energies are measured. These analyses account for unimolecular decay rates, internal energy of reactant ions, and multiple ion-molecule collisions. Ab initio calculations for a number of geometric conformations of the M+(L) complexes were determined at the B3LYP/6-311G(d,p) level with single-point energies calculated at MP2(full), B3LYP, and B3P86 levels using a 6-311+G(2d,2p) basis set. Theoretical bond energies show good agreement with the experimental bond energies, which establishes that the zwitterionic form of the alkali metal cation/amino acid, the lowest energy conformation, is formed in all cases. Despite the increased conformational mobility in the Pip systems, the Li+, Na+, and K+ complexes of Pro show higher binding energies. A meticulous examination of the zwitterionic structures of these complexes provides an explanation for the stability of the five-membered ring complexes.