C-H?π interactions in the [Co(N-(2-aminomethylpyridyl)ethylenediamine)(2- aminomethylpyridine)Cl] system: syntheses, 2D NMR, X-ray structures and energy minimizations

Ten asymmetric isomers exist for [Co(pema)(ampy)Cl]²⁺ (pema=N-(2-aminomethylpyridyl)ethylenediamine, ampy=2-aminomethylpyridine) which involve unsymmetrical triamine and diamine ligands. Four of these have been synthesized, two facial (f3, f2^′) and two mer (m3 and m4) isomers. Ab initio energy calculations for the [Co(pema)(ampy)Cl]²⁺ and [Co(pema)(ampy)OH]²⁺ systems show that the isomers containing a C-H?π interaction are the more stable forms. The f3 is the most stable isomer in the chloro system and the m3 form in the hydroxo system. The structures are deduced from the 2D NMR spectra and confirmed by the X-ray crystal structure determinations for the four chloro isomers.     

Theoretical investigations of the H···π and X (X = F,Cl, Br,I)···π complexes between hypohalous acids and benzene

The H···π and X (X = F, Cl, Br, I)···π interactions between hypohalous acids and benzene are investigated at the MP2/6-311++G(2d,2p) level. Four hydrogen-bonded and three halogen-bonded complexes were obtained. Ab initio calculations indicate that the X···π interaction between HOX and C₆H₆ is mainly electrostatically driven, and there is nearly an equal contribution from both electrostatic and dispersive energies in the case of XOH–C₆H₆ complexes. Natural bond orbital (NBO) analysis reveals that there exists charge transfer from benzene to hypohalous acids. Atom in molecules (AIM) analysis locates bond critical points (BCP) linking the hydrogen or halogen atom and carbon atom in benzene.     

Structures and magnetic property studies of four copper(II) and nickel(II) supramolecular complexes derived from diphenic acid constructed by C-H?π and π-π interactions

Four one-dimensional metal-organic polymers derived from diphenic acid (H₂dpa) were synthesized in the presence of auxiliary ligands, [Cu(dpa)CH₃OH](1), [Ni(dpa)CH₃OH] (2), [Cu(bipy)₂(Hdpa)₂(H₂O)₂] (3) and [Ni(bipy)₂(Hdpa)₂(H₂O)₂] (4) (bipy = 4, 4′-bipyridine). The dinuclear paddle-wheel second building units (SBUs) constructed by four dpa²⁻ ligands in complexes 1 and 2 are linked by dpa²⁻ into double chains, which are connected by C-H?π interactions forming a two-dimensional rhombic porous structure. In complexes 3 and 4, the metal ions are connected by bipy ligands, and the grid-like network was formed with the π-π interactions between the adjacent phenyl rings of Hdpa⁻. For 1 and 2, there are strong antiferromagnetic interactions within Cu-Cu and Ni-Ni dimers. It is also strong antiferromagnetic interactions between the dimmers of Cu₂ in 1, while it is weaker of those of Ni₂ in 2. Weaker antiferromagnetic interactions exist among Cu-Cu and Ni-Ni in 3 and 4, in which bipy is the effective coupling media. Thermally gravimetric analyses and differential thermal analyses indicate that the four complexes are all thermal stable.     

Chloroquine Stimulates Cl? Secretion by Ca2+ Activated Cl? Channels in Rat Ileum

Chloroquine (CQ), a bitter tasting drug widely used in treatment of malaria, is associated gastrointestinal side effects including nausea or diarrhea. In the present study, we investigated the effect of CQ on electrolyte transport in rat ileum using the Ussing chamber technique. The results showed that CQ evoked an increase in short circuit current (I_SC) in rat ileum at lower concentration (≤5×10⁻⁴ M ) but induced a decrease at higher concentrations (≥10⁻³ M). These responses were not affected by tetrodotoxin (TTX). Other bitter compounds, such as denatoniumbenzoate and quinine, exhibited similar effects. CQ-evoked increase in I_SC was partly reduced by amiloride(10⁻⁴ M), a blocker of epithelial Na⁺ channels. Furosemide (10⁻⁴ M), an inhibitor of Na⁺-K⁺ -2Cl⁻ co-transporter, also inhibited the increased I_SC response to CQ, whereas another Cl⁻ channel inhibitor, CFTR(inh)-172(10⁻⁵M), had no effect. Intriguingly, CQ-evoked increases were almost completely abolished by niflumic acid (10⁻⁴M), a relatively specific Ca²⁺-activated Cl⁻ channel (CaCC) inhibitor. Furthermore, other CaCC inhibitors, such as DIDS and NPPB, also exhibited similar effects. CQ-induced increases in I_SC were also abolished by thapsigargin(10⁻⁶M), a Ca²⁺ pump inhibitor and in the absence of either Cl⁻ or Ca²⁺ from bathing solutions. Further studies demonstrated that T2R and CaCC-TMEM16A were colocalized in small intestinal epithelial cells and the T2R agonist CQ evoked an increase of intracelluar Ca²⁺ in small intestinal epithelial cells. Taken together, these results demonstrate that CQ induces Cl⁻ secretion in rat ileum through CaCC at low concentrations, suggesting a novel explanation for CQ-associated gastrointestinal side-effects during the treatment of malaria.     

π Delocalization in iridathiabenzenes

Fenske-Hall calculations were carried out for (PEt₃)₃Ir(C₇H₉) (1), [(PEt₃)₃Ir(C₆H₈S)]⁺ (2), [(S-t-but)(PEt₃)₂]Ir(C₆H₈S) (3), and [(S-t-but)(PMet₃)₃]Ir(C₆H₈S) (4) in order to compare the degree of π delocalization in the metallathiacycle rings of (2) and (3). In comparison to (1), a true iridabenzene and (4), an iridathiacyclobutadiene, the π ring systems in (2) and (3) are considerably more localized than the π system in (1) but are not totally localized. Strong metal-sulfur bonding in (2) disrupts the π ring system and results in some localization of the ring π bonds. The introduction of the donor thiolate ligand in (3) disrupts the ring of π system even more by destabilizing the metal orbitals used for metal-sulfur interactions. This weakens the metal-sulfur interaction seen in (2) and leads to even more localization of the ring π system in (3).     

Acetylcholine-activated Cl? Channel in the Chara Tonoplast

Acetylcholine has long been suggested to play a role in controlling physiological processes in plants, but no mechanism has been shown for its action. We show here that a chloride channel in the tonoplast (vacuolar membrane) of Chara corallina responds to acetylcholine. The channel has a conductance of 45 pS. The effect of acetylcholine is enhanced by nicotine, with the open probability increasing from 0.05 in the presence of 4 mM acetylcholine to 0.3 in the presence of 4 mM acetylcholine + 6 mM nicotine. Some effects of acetylcholine were seen at concentrations as low as 20 microM, with a maximum effect between 1 and 10 mM. In the intact cell, acetylcholine prolongs the depolarized phase of the action potential. We propose that this acetylcholine-gated channel has evolved separately from the mammalian acetylcholine-gated channel, and suggest that this represents a third form of acetylcholine signal transduction, after the nicotinic and muscarinic pathways in animal systems.     

A sterically congested aryltrimethylstannane - Synthesis, reactivity, transmetalation and CH-π interaction

The synthesis of a novel sterically congested tetraorganotin compound, (4-tert-butyl-2,6-dimesitylphenyl)trimethylstannane (1), is reported and its reactivity with special focus on transmetalation studied. The reaction of compound 1 with reagents such as HgCl₂, BiCl₃ and HOTf gave (4-tert-butyl-2,6-dimesitylphenyl)dimethyltin chloride (2) and (4-tert-butyl-2,6-dimesitylphenyl)dimethyltin triflate (3), respectively, as a result of selective tin-methyl bond cleavage. Less bulky aryltrimethyltin derivatives react with BiCl₃ to give both tin-methyl and tin-aryl bond cleavage. Hydrolysis of compound 3 proceeds slowly to give bis-(4-tert-butyl-2,6-dimesitylphenyl)dimethyl stannoxane (5) via the intermediate (4-tert-butyl-2,6-dimesitylphenyl)dimethyltin hydroxide (4). All terphenyldimethyltin derivatives that were characterized by single crystal X-ray diffraction analysis show C-H?π interactions. Based on these results, the optimum C-H?π distance (C?centroid_aryl distance) is suggested to be in the range 3.4 and 3.5 Å.     

Modulation of Voltage-dependent Properties of a Swelling-activated Cl? Current

We used the patch-clamp technique to study the voltage-dependent properties of the swelling-activated Cl⁻ current (I _Cl,swell) in BC₃H1 myoblasts. This Cl⁻ current is outwardly rectifying and exhibits time-dependent inactivation at positive potentials (potential for half-maximal inactivation of +75 mV). Single-channel Cl⁻ currents with similar voltage-dependent characteristics could be measured in outside-out patches pulled from swollen cells. The estimated single-channel slope conductance in the region between +60 and +140 mV was 47 pS. The time course of inactivation was well described by a double exponential function, with a voltage-independent fast time constant (∼60 ms) and a voltage-dependent slow time constant (>200 ms). Recovery from inactivation, which occurred over the physiological voltage range, was also well described by a double exponential function, with a voltage-dependent fast time constant (10–80 ms) and a voltage-dependent slow time constant (>100 ms). The inactivation process was significantly accelerated by reducing the pH, increasing the Mg²⁺ concentration or reducing the Cl⁻ concentration of the extracellular solution. Replacing extracellular Cl⁻ by other permeant anions shifted the inactivation curve in parallel with their relative permeabilities (SCN⁻ > I⁻ > NO₃ ⁻ > Cl⁻ >> gluconate). A leftward shift of the inactivation curve could also be induced by channel blockers. Additionally, the permeant anion and the channel blockers, but not external pH or Mg²⁺, modulated the recovery from inactivation. In conclusion, our results show that the voltage-dependent properties of I _Cl,swell are strongly influenced by external pH , external divalent cations, and by the nature of the permeant anion.     

Cellular Mechanism Underlying Formaldehyde-Stimulated Cl? Secretion in Rat Airway Epithelium

Background

Recent studies suggest that formaldehyde (FA) could be synthesized endogeneously and transient receptor potential (TRP) channel might be the sensor of FA. However, the physiological significance is still unclear.

Methodology/Principal Findings

The present study investigated the FA induced epithelial Cl^- secretion by activation of TRPV-1 channel located in the nerve ending fiber. Exogenously applied FA induced an increase of I _SC in intact rat trachea tissue but not in the primary cultured epithelial cells. Western blot and immunofluorescence analysis identified TRPV-1 expression in rat tracheal nerve ending. Capsazepine (CAZ), a TRPV-1 specific antagonist significantly blocked the I _SC induced by FA. The TRPV-1 agonist capsaicin (Cap) induced an increase of I _SC, which was similar to the I _SC induced by FA. L-703606, an NK-1 specific inhibitor and propranolol, an adrenalin β receptor inhibitor significantly abolished the I _SC induced by FA or Cap. In the ion substitute analysis, FA could not induce I _SC in the absence of extracelluar Cl^-. The I _SC induced by FA could be blocked by the non-specific Cl^- channel inhibitor DPC and the CFTR specific inhibitor CFTR_i-172, but not by the Ca²⁺-activated Cl^- channel inhibitor DIDS. Furthermore, both forskolin, an agonist of adenylate cyclase (AC) and MDL-12330A, an antagonist of AC could block FA-induced I _SC.

Conclusion

Our results suggest that FA-induced epithelial I _SC response is mediated by nerve, involving the activation of TRPV-1 and release of adrenalin as well as substance P.     

Metal(II)-organic coordination polymers with two distinct atropisomeric building units from an axially prochiral inner salt through interchain C-H?X hydrogen bonds (X = O, Cl; metal = cobalt, nickel)

Two isostructural photoluminescent metal-organic coordination polymers, namely, [M(H-mpypdc)(Cl)(H₂O)₃]_n (mpypdc = 2,6-dimethyl-4-(pyridin-4-yl)pyridine-3,5-dicarboxylate; M = Co (2) and Ni (3)), were synthesized from H₂mpypdc (1), and characterized by single crystal X-ray analyses. New ligand 1 is an inner salt. In the metal-organic coordination polymeric chains, two distinct S- and R-atropisomeric units are generated from the axially prochiral 1 through C-H?X (X = O, Cl) hydrogen bonds. There have interesting 2D supramolecular networks [M(Cl)(H₂O)₂]_n in the crystal structures of title compounds. The photoluminescence of new compounds are also investigated in solid state at ambient temperature.     

Cation-π and π-π stacking interactions allow selective inhibition of butyrylcholinesterase by modified quinine and cinchonidine alkaloids

Scaffold varied quaternized quinine and cinchonidine alkaloid derivatives were evaluated for their selective butyrylcholinesterase (BChE) inhibitory potential. K_i values were between 0.4–260.5 μM (non-competitive inhibition) while corresponding K_ivalues to acetylcholinesterase (AChE) ranged from 7.0–400 μM exhibiting a 250-fold selectivity for BChE.Docking arrangements (GOLD, PLANT) revealed that the extended aromatic moieties and the quaternized nitrogen of the inhibitors were responsible for specific π–π stacking and π–cation interactions with the choline binding site and the peripheral anionic site of BChE’s active site.     

Silver(I) complexes of dibenzo-18-crown-6-ether having cation-π and π-π interactions

Three silver(I) complexes of dibenzo-18-crown-6-ether (DB[18]C6), [Ag(DB[18]C6)(ClO₄)](THF) (1), [Ag(DB[18]6)(CF₃SO₃)]₂(acetone)₂ (2) and [Ag(DB[18]C6)(CF₃COO)]₂(AgCF₃COO)₂ (3) have been synthesized in different solvents and characterized structurally. In each complex, silver ions prefer an octahedral coordination geometry and form close dinuclear complex with DB[18]C6 based on cation-π interaction in η²-fashion. In particular, the coordination unit involving σ bonding at an oxygen group and π-π bonding between two benzene rings is quite unique.     

Quantum-Chemical Analysis of C-H…O and C-H…N Interactions in RNA Base Pairs—H-Bond Versus Anti-H-Bond Pattern

Abstract

Geometries and interaction energies of unusual UU and AA base pairs with one standard hydrogen bond (H-bond) and additional C-H…O or C-H…N contacts have been determined by quantum-chemical methods taking into account electron correlation. Whereas the C-H bond length in the UU C-H…O contact increases upon complex formation (H-bond pattern), the C-H bond of the AA C-H….N interaction is shortened (anti-H-bond pattern). The same properties are found for model complexes between U or A and formaldehyde that have intermolecular C-H…acceptor contacts but no standard H-bonds. Both the C-H…acceptor H-bond and anti-H-bond interactions are attractive. A possible influence of the donor CH group charge distribution on the interaction pattern is discussed.     

A (U)MP2(full) and (U)CCSD(T) theoretical investigation into the substituent effects on the intermolecular T-shaped F–H…π interactions between HF and LBBL (L = ?H, ∶CO, :NN, –Cl, –CN and –NC)

The substituent effects on the intermolecular T-shaped F-H...π interactions are investigated between HF and LBBL (L = -H, : CO, :NN, -Cl, -CN and -NC) using the (U)MP2(full) and (U)CCSD(T) methods with the 6-311++G(2 d,p) basis set. The B ≡ B triple-bond contraction is found in the complexes with lone-pair-electron donors while the B = B double-bond is lengthened in the systems with the single-electron substituents upon complexation. The T-shaped F-H...π interaction energies follow the order of ClB = BCl...HF>HB = BH...HF>NNB ≡ BNN...HF>OCB ≡ BCO...HF>CNB = BNC...HF>NCB = BCN...HF. The electron-donating substituents : CO and :NN increases electron density of the B ≡ B triple bond by the delocalization interaction E ((2)) π ((CO/NN) → Lp(B)) while the electron-withdrawing substituents -CN and -NC decrease electron density of the B = B double bond by means of the π-π conjugative effect. The analyses of the APT atomic charge, "truncated" model, natural bond orbital (NBO), atoms in molecules (AIM) and electron density shifts reveal the nature of the substituent effect and explain the origin of the B ≡ B bond contraction.     

Ruthenium-thiobase complexes: Synthesis, spectroscopy, density functional studies for trans,cis,cis-[Ru(AsPh3)2 (N,S-2-Thiopyrimidinato)2] and structural analysis of selected weak C-H?N and C-H?S interactions

The reaction of trans-[Ru^III(AsPh₃)₂Cl₃(CH₃OH)] (green powder) with 2-thiopyrimidine-1,3, HTPYM, in ethanol, produced red crystals of trans,cis,cis-[Ru^II(AsPh₃)₂(N,S-2-thiopyrimidinato)₂]. The compound has two TPYM⁻ chelating anions in the equatorial plane, whereas the As atoms occupy the apical positions. It is stable in the solid state but the yellow chloroform solutions turn to green quickly in air atmosphere. The Ru-As, Ru-S and Ru-N bond distances average 2.432(1), 2.440(2) and 2.078(6) Å, respectively. The AsPh₃ ligands assume a semi-trefoil C₁ arrangement and have C-H?S intra-molecular hydrogen bond type interactions to TPYM⁻ ligands. These latter ligands are also involved in C-H?N and C-H?S interactions that pair two thiobase ligands via an unusual way. Density functional computational studies on [Ru(AsH₃)₂(N,S-TPYM)₂] model molecules show that the cis,cis,trans isomer is more stable than the trans,cis,cis one by some 5 kcal mol⁻¹.     

Theoretical study of X- · 1 · YF (1 = triazine,X = Cl,Br and I,Y = H,Cl, Br,I, PH2 and AsH2): noncovalently electron-withdrawing effects on anion-arene interactions

The ternary complexes X^- · 1 · YF (1 = triazine, X = Cl, Br and I, Y = H, Cl, Br, I, PH₂ and AsH₂) have been investigated by MP2 calculations to understand the noncovalently electron-withdrawing effects on anion-arene interactions. The results indicate that in binary complexes (1 · X^-), both weak σ-type and anion-π complexes can be formed for Cl^- and Br^-, but only anion-π complex can be formed for I^-. Moreover, the hydrogen-bonding complex is the global minimum for all three halides in binary complexes. However, in ternary complexes, anion-π complex become unstable and only σ complex can retain in many cases for Cl^- and Br^-. Anion-π complex keeps stable only when YF = HF. In contrast with binary complexes, σ complex become the global minimum for Cl^- and Br^- in ternary complexes. These changes in binding mode and strength are consistent with the results of covalently electron-withdrawing effects. However, in contrast with the covalently electron-withdrawing substituents, Cl^- and Br^- can attack the aromatic carbon atom to form a strong σ complex when the noncovalently electron-withdrawing effect is induced by halogen bonding. The binding behavior for I^- is different from that for Cl^- and Br^- in two aspects. First, the anion-π complex for I^- can also keep stable when the noncovalent interaction is halogen bonding. Second, the anion-π complex for I^- is the global minimum when it can retain as a stable structure.     

The Ca,Cl, Mg,Na, and P Mass Fractions in Human Bone Affected by Ewing’s Sarcoma

The Ca, Cl, Mg, Na, and P contents and Ca/P, Ca/Mg, Ca/Na, Cl/Ca, and Cl/Na ratios in samples of intact bone, inflamed bone, and Ewing’s sarcoma tissue were investigated by neutron activation analysis with high-resolution spectrometry of short-lived radionuclides. In Ewing’s sarcoma tissue, the mass fractions of Cl and Na are higher and the mass fractions of Ca and Mg are lower than those of both normal and inflamed bone tissues. It was shown that the levels of Ca and Cl mass fractions and also levels of the Ca/Cl and Cl/Na ratios can be used as an additional test for differential diagnosis between inflamed (or normal) bone and Ewing’s sarcoma.     

Current-voltage curve of electrogenic Cl− pump predicts voltage-dependent Cl− efflux inAcetabularia

Summary The current-voltage relationship of carrier-mediated, passive and active ion transport systems with one charge-carrying pathway can exactly be described by a simple reaction kinetic model. This model consists of two carrier states (one inside, one outside) and two pairs (forwards and backwards) of rate constants: a voltage-dependent one, describing the transport of charge and a voltage-insensitive one, summarizing all the other (voltage-independent) reactions. For the electrogenic Cl^– pump inAcetabularia these four rate constants have been determined from electrical measurements of the current-voltage relationship of the pump (Gradmann, Hansen & Slayman, 1981;in: Electrogenic Ion Pumps, Academic Press, New York). The unidirectional Cl^– efflux through the pump can also be calculated by the availiable reaction kinetic parameters.³⁶Cl^– efflux experiments on singleAcetabularia cells with simultaneous electrical stimulation (action potentials) and recording, demonstrate the unidirectional Cl^– efflux to depend on the membrane potential. After subtraction of an efflux portion which bypasses the pump, agreement is found between the measured flux-voltage relationship and the theoretical one as obtained from the reaction kinetic model and its parameters from the electrical data.     

Cl? and K+ channels and their role in primary brain tumour biology

Profound cell volume changes occur in primary brain tumours as they proliferate, invade surrounding tissue or undergo apoptosis. These volume changes are regulated by the flux of Cl⁻ and K⁺ ions and concomitant movement of water across the membrane, making ion channels pivotal to tumour biology. We discuss which specific Cl⁻ and K⁺ channels are involved in defined aspects of glioma biology and how these channels are regulated. Cl⁻ is accumulated to unusually high concentrations in gliomas by the activity of the NKCC1 transporter and serves as an osmolyte and energetic driving force for volume changes. Cell volume condensation is required as cells enter M phase of the cell cycle and this pre-mitotic condensation is caused by channel-mediated ion efflux. Similarly, Cl⁻ and K⁺ channels dynamically regulate volume in invading glioma cells allowing them to adjust to small extracellular brain spaces. Finally, cell condensation is a hallmark of apoptosis and requires the concerted activation of Cl⁻ and Ca²⁺-activated K⁺ channels. Given the frequency of mutation and high importance of ion channels in tumour biology, the opportunity exists to target them for treatment.