Biologically active, synthetic ion transporters

The compelling chemical goal of modeling protein channel behavior has led to synthetic compounds that are true ion channels. Although they largely lack the selectivity and sophistication of highly evolved proteins, they successfully perform a variety of biological functions. This tutorial review describes these novel structures and their activity in living systems. Different channel structures show antibacterial to anticancer activity when tested against a variety of cell types.     

Development of synthetic membrane transporters for anions

The development of low molecular weight anion transporters is an emerging topic in supramolecular chemistry. The major focus of this tutorial review is on synthetic chloride transport systems that operate in vesicle and cell membranes. The transporters alter transmembrane concentration gradients, and thus they have applications as reagents for cell biology research and as potential chemotherapeutic agents. The molecular designs include monomolecular channels, self-assembled channels and mobile carriers. Also discussed are the experimental assays that measure transport rates across model bilayer membranes.     

Cyclic tetramers composed of rhodium(III), iridium(III), or ruthenium(II) half-sandwich and 6-purinethiones

Six new cyclic tetranuclear complexes [[M(Cp*)(L)](4)](4+) and [[Ru(II)(L)(cymene)](4)](4+) [Cp* = eta(5)-C(5)Me(5), cymene = eta(6)-p-MeC(6)H(4)Pr(i); M = Rh(III) and Ir(III); HL = 6-purinethione (H(2)put) and 2-amino-6-purinethione (H(2)aput)] were prepared in a self-assembly manner and characterized by NMR spectroscopy, electrospray ionization mass spectrometry, and X-ray crystal structure analysis. The two crystal structures of [[Rh(Cp*)(H(0.5)put)](4)](CF(3)SO(3))(2) and [[Ir(Cp*)(Haput)](4)](CF(3)SO(3))(4) revealed that they have similar S(4) structures with an alternate chirality array of CACA, and all ligands adopt a mu-1kappaN(9):2kappa(2)S(6),N(7) coordination mode. The orientations of the four bridging ligands are alternately up and down, and they form a central square cavity. Interestingly, the cationic tetramers of the former are stacked up along the c axis, resulting in an infinite channel-like cavity. The driving force of this stacking is due to intermolecular double hydrogen bonds [N(1)-H...N(21) = 2.752(4) A] at both sides of the cavity. In the two Rh(III)- and Ru(II)-H(2)aput systems, it turned out that the dimeric species are dominantly formed in the reaction solutions but finally convert into the tetrameric species.     

Adsorption of Cu(II), Zn(II), Ni(II), Pb(II), and Cd(II) from aqueous solution on Amberlite IR-120 synthetic resin

The adsorption of copper(II), zinc(II), nickel(II), lead(II), and cadmium(II) on Amberlite IR-120 synthetic sulfonated resin has been studied at different pH and temperatures by batch process. The effects of parameters such as amount of resin, resin contact time, pH, and temperature on the ion exchange separation have been investigated. For the determination of the adsorption behavior of the resin, the adsorption isotherms of metal ions have also been studied. The concentrations of metal ions have been measured by batch techniques and with AAS analysis. Adsorption analysis results obtained at various concentrations showed that the adsorption pattern on the resin followed Freundlich isotherms. Here we report the method that is applied for the sorption/separation of some toxic metals from their solutions.     

Fe(III) coordination properties of a new saccharide-based exocyclic trihydroxamate analogue of ferrichrome

The coordination chemistry of a saccharide-based ferrichrome analogue, 1-O-methyl-2,3,4-tris-O-[4-(N-hydroxy-N-methylcarbamoyl)-n-butyrate]-alpha-d-glucopyranoside (H(3)L), is reported, along with its pK(a) values, Fe(III) and Fe(II) chelation constants, and aqueous-solution speciation as determined by spectrophotometric and potentiometric titration techniques. The use of a saccharide platform to synthesize a hexadentate trihydroxamic acid chelator provides some advantages over other approaches to ferrichrome models, including significant water solubility and hydrogen-bonding capability of the backbone that can potentially provide favorable receptor recognition and biological activity. The pK(a) values for the hydroxamate moieties were found to be similar to those of other trihydroxamates. Proton-dependent Fe(III)-H(3)L and Fe(II)-H(3)L equilibrium constants were determined using a model involving the sequential protonation of the iron(III)- and iron(II)-ligand complexes. These results were used to calculate the formation constants, log beta(110) = 31.86 for Fe(III)L and 12.1 for Fe(II)L(-). The calculated pFe value of 27.1 indicates that H(3)L possesses an Fe(III) affinity comparable to or greater than those of ferrichrome and other ferrichrome analogues and is thermodynamically capable of removing Fe(III) from transferrin. E(1/2) for the Fe(III)L/Fe(II)L(-) couple was determined to be -436 mV from quasi-reversible cyclic voltammograms at pH = 9, and the pH-dependent E(1/2) profile was used to determine the Fe(II)L(-) protonation constants.     

Chocolate HILIC phases: development and characterization of novel saccharide-based stationary phases by applying non-enzymatic browning (Maillard reaction) on amino-modified silica surfaces

Novel saccharide-based stationary phases were developed by applying non-enzymatic browning (Maillard Reaction) on aminopropyl silica material. During this process, the reducing sugars glucose, lactose, maltose, and cellobiose served as “ligand primers”. The reaction cascade using cellobiose resulted in an efficient chromatographic material which further served as our model Chocolate HILIC column. (Chocolate refers to the fact that these phases are brownish.) In this way, an amine backbone was introduced to facilitate convenient manipulation of selectivity by additional attractive or repulsive ionic solute–ligand interactions in addition to the typical HILIC retention mechanism. In total, six different test sets and five different mobile phase compositions were investigated, allowing a comprehensive evaluation of the new polar column. It became evident that, besides the so-called HILIC retention mechanism based on partition phenomena, additional adsorption mechanisms, including ionic interactions, take place. Thus, the new column is another example of a HILIC-type column characterized by mixed-modal retention increments. The glucose-modified materials exhibited the relative highest overall hydrophobicity of all grafted Chocolate HILIC columns which enabled retention of lipophilic analytes with high water content mobile phases.     

Molecular rotors as a class of generally highly active ion transporters

We describe here a class of unconventional ion transporters,molecular rotors that transport ions through a rotating function rather than via traditional carrier...     

Aggregation behavior and dynamics of synthetic amphiphiles that self-assemble to anion transporters

The amphiphilic heptapeptides-referred to as synthetic anion transporters (SATs)-mediate chloride transport in planar lipid bilayer membranes, synthetic liposomes, and mammalian cells. The SATs described have the general formula R1(2)NCOCH2OCH2CO-(Gly)3-Pro-(Gly)3-OR2. Substitution at R1 and R2 with various aliphatic or aromatic groups alters the ability of SATs to transport chloride through a phospholipid bilayer membrane. Despite extensive structure-activity relationship studies concerning Cl(-)-mediated transport by SATs, relatively little was known about the mechanism of insertion and pore-formation in the membrane. In the current study, the mechanistic behavior of SATs was investigated in aqueous solution and at the air-water interface. In the latter case, Langmuir trough studies and Brewster angle microscopy (BAM) revealed the extent of monolayer stability and organization for SATs. Dynamic light scattering and transmission electron microscopy (TEM) confirmed these results and defined the aggregation behavior of SATs in solution. SAT derivatives that showed low chloride transport activity organized into stable monolayers at the air-water interface, while more active SATs formed less stable monolayers. The relationship between intermolecular organization of SATs and pore-formation in the membrane is discussed along with its implications for chloride transport.     

FeII2(PO4)(OH), a synthetic analogue of wolfeite

This paper reports the hydrothermal synthesis and crystal structure refinement of diiron(II) phosphate hydroxide, Fe^II₂(PO₄)(OH), obtained at 1063 K and 2.5 GPa. This phosphate is the synthetic analogue of the mineral wolfeite, and has a crystal structure topologically identical to those of minerals of the triplite–triploidite group. The complex framework contains edge‐ and corner‐sharing FeO₄(OH) and FeO₄(OH)₂ polyhedra, linked via corner‐sharing to the PO₄ tetrahedra (average P—O distances are between 1.537 and 1.544 Å). Four five‐coordinated Fe sites are at the centers of distorted trigonal bipyramids (average Fe—O distances are between 2.070 and 2.105 Å), whereas the coordination environments of the remaining Fe sites are distorted octahedra (average Fe—O distances are between 2.146 and 2.180 Å). The Fe—O distances are similar to those observed in natural Mg‐rich wolfeite, except for two Fe—O bond distances, which are significantly longer in synthetic Fe²⁺₂(PO₄)(OH).     

The Synthesis of Unusual Organic Molecules Using Cyclic Peroxides. New synthetic methods (3)

The photodecarboxylation of malonyl peroxides into α-lactones^[1] and the thermal conversion of the 1,4-endo-peroxide 4,5-epoxy-3,6-epidioxy-1-cyclohexene into the novel benzene trioxide^[2] are two recent examples of the potential of cyclic peroxides in the synthesis of unusual organic molecules. The former transformation entails a fragmentation, the latter a rearrangement process. Most reported examples fall into one of these two gross reaction types. Of the numerous examples that have been reported in the literature during the last two decades, only those shall be focused on that lead to unusual compounds or constitute efficient syntheses of known compounds, in order to stress the convenience of cyclic peroxides in the synthesis of organic compounds.     

Cyclic (alkyl)(amino)carbene gold(I) complexes: A synthetic and structural investigation

A series of mono- and dicarbene gold(I) complexes of types Au(CAAC)(Cl) [CAAC = cyclic (alkyl)(amino)carbene] (1) and [Au(CAAC)₂]⁺[X]^? (X = Cl, AuCl₂) (2) have been prepared through reaction of AuCl(SMe₂) with free carbenes a–e, and structurally characterized by single X-ray diffraction studies (1a, 1b, 2d, 2e). In addition two new free cyclic (alkyl)(amino)carbenes (c and e) have been synthesized.     

Cyclic oxonium derivatives of polyhedral boron hydrides and their synthetic applications

Cyclic oxonium derivatives of polyhedral boron hydrides are a relatively new class of boron compounds. They have great potential for the modification of various types of organic and bioorganic molecules and the synthesis of compounds that could be used in different fields from the treatment of nuclear wastes to the treatment of cancer. In the present Perspective we would like to present an overview of the results of the preparation and synthetic application of these compounds.     

An Electron‐Rich Cyclic (Alkyl)(Amino)Carbene on Au(111), Ag(111), and Cu(111) Surfaces

The structural properties and binding motif of a strongly σ‐electron‐donating N‐heterocyclic carbene have been investigated on different transition‐metal surfaces. The examined cyclic (alkyl)(amino)carbene (CAAC) was found to be mobile on surfaces, and molecular islands with short‐range order could be found at high coverage. A combination of scanning tunneling microscopy (STM), X‐ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculations highlights how CAACs bind to the surface, which is of tremendous importance to gain an understanding of heterogeneous catalysts bearing CAACs as ligands.     

Cyclic sulfamidates as versatile lactam precursors. An evaluation of synthetic strategies towards (-)-aphanorphine

A full account of studies which led to the efficient asymmetric synthesis of (-)-aphanorphine is reported. Two routes to the key cyclic sulfamidate intermediate are described, the first was based on a chiral auxiliary approach and the second utilised asymmetric hydrogenation methodology. A range of C(3)-substituted lactams (, and ) were synthesised and evaluated as precursors for Pd(0) catalysed entries (based on (i) alpha-arylation of a lactam enolate and (ii) reductive Heck reaction) to the 3-benzazepine core of . These approaches were less effective than an aryl radical cyclisation which allowed the completion of a synthesis of in 12 steps from anisaldehyde.     

Enhancement of antimicrobial activity by synthetic ion channel synergy

Hydraphile synthetic ion channels were found to enhance the cytotoxicity to E. coli and B. subtilis of erythromycin, kanamycin, rifampicin, and tetracycline when co-administered with the antibiotic at sublethal concentrations of channel.     

Extrapolation of molar equilibrium constants to zero ionic strength and parameters dependent on it. Copper(II), nickel(II), hydrogen(I) complexes with glycinate ion and calcium(II), hydrogen(I) complexes with nitrilotriacetate ion

The stability constants of the complexes of glycinate ion with copper(II), nickel(II) and hydrogen(I) and of nitrilotriacetate ion with calcium(II) and hydrogen(I) and the ionic product of water (K(w)) were determined potentiometrically. The measurements were carried out at 25.0 degrees C in four different ionic strengths up to I (= I(c)) = 2.50 and two different ionic media (KNO(3) and (CH(3))(4)NNO(3)). Extrapolation of equilibrium constants to zero ionic strength and ionic strength corrections to equilibrium constants were carried out with the data obtained from both media using the TEC (thermodynamic equilibrium constant) equation and computer program. The constants of the potassium complexes with nitrilotriacetic acid at low ionic strength are also given. Successful attempts to predict equilibrium constants for other ionic media using TEC parameters and the procedure of the specific ion-interaction theory (SIT) are given. The variations of equilibrium constants with the ionic strengths and ionic media are demonstrated.     

α-羟醛的新合成方法研究

报道了一种制备α-羟醛的未见文献报道的合成方法, 以乙二胺和α-羟基羧酸为原料, 经咪唑啉中间体, 得到α-羟醛。讨论了反应条件、取代基对咪唑啉中间体还原水解反应产率的影响。