A New Generation of "Cholaphanes": Steroid-Derived Macrocyclic Hosts with Enhanced Solubility and Controlled Flexibility

The macrocyclic "cholaphanes" 3a-c were synthesized from the inexpensive steroid cholic acid. Like earlier relatives they feature substantial cavities with inward-directed hydroxyl groups, suitable for binding polar molecules such as carbohydrates in nonpolar media. New features are the externally directed alkyl chains, promoting solubility in organic solvents, and (in the case of 3b/c) reduced conformational freedom resulting from truncation of the steroidal side-chain. In particular, modeling shows that the smallest macrocycle 3c possesses very little flexibility, preferring an open conformation which is also revealed in the X-ray crystal structure of its pentahydrate. NMR studies indicated that all three cholaphanes form 1:1 complexes with octyl beta-D-glucoside in CDCl(3), with K(a) = 600-1560 M(-)(1). Cholaphanes 3b/c proved able to extract methyl beta-D-glucoside from aqueous solutions into CHCl(3). The transport of methyl beta-D-glucoside across a chloroform barrier was also demonstrated for 3c.     

X-Ray Structure and Proton NMR Study of a Hexacoordinated Lithium Complex

The structure of the lithium complex with1,3,5-tris[oxymethylene(N,N-dicyclohexyl)carboxyamido]cyclohexanehas been determined by the X-ray method.The compound is triclinic, space group P¯1,a = 15.623(3), b = 19.279(4),c = 19.295(4)Å = 102.32(3), = 92.45(3), = 105.67(3)0, V = 5436(2)Å3, Z = 4. Itscomposition is represented by the formulaC48H82N3O6LiI 0.5H2O. The lithium cationis encapsulated in a polar pseudo-cavity of six oxygen atoms of the ligandmolecule and displays a distorted trigonal prism coordination. The conformationof the ligand in the solid state complex has been compared with the conformationof the complex in solution determined by 1H-NMR measurements.Supplementary data relevant to this publication have been deposited with the British Library, No. SUP 82224 (21 pages).     

A simplified device for protein identification by microcapillary gradient liquid chromatography-tandem mass spectrometry

A simplified device and procedure have been developed for microcapillary gradient liquid chromatography-tandem mass spectrometry (LC-MS/MS). This procedure has proved useful in identifying low level quantities of proteins from sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel bands. Microelectrospray needles are packed with reversed-phase resin and function both as a high performance liquid chromatography (HPLC) column and a nanospray mass spectrometer tip when interfaced between an HPLC and ion trap mass spectrometer. Variable submicroliter flow rates are generated by flow splitting between the microelectrospray capillary and an HPLC system. A manual injector is used to inject a protein digest mixture that binds to the column and is then washed at a high flow rate (2 microL/min post split). Gradient elution of bound peptides was initiated by the injection of a filled loop of 70% v/v methanol (5 microL) concomitant with a reduction of flow rate (0.1 microL/min post split). This forms a diffusion-dependent gradient of variable length (typically 15-30 min in length) depending upon the final flow rate. Chromatographic separations of a standard solution digest demonstrate that this diffusion-dependent gradient provides reasonable separations such that multiple peptide identifications by MS/MS can be obtained. Application of this methodology to the analysis of several in-gel-digested gel-separated proteins is presented to demonstrate its utility.     

Unsymmetrical selenides from selenocyanates and methyl grignard

The addition of methyl Grignard to diethyl acetamido(cyanoselenobenzyl)malonates 3 and 4 at ?78° followed by hydrolysis yields the 3-(4-and 3-methylselenophenyl)alanines 1 and 2.     

Determining the chromophore in the amylopectin–iodine complex by theoretical and experimental studies

A partial hydrolysis of amylose followed by the addition of iodine provides a spectrum almost identical to that of the amylopectin–iodine (API) complex suggesting the involvement of smaller “amylose-like” units in the API complex. Our theoretical studies on different polyiodine and polyiodide species suggest that a nearly linear I₄ unit stabilized within the cavity of a small “amylose-like” helix is responsible for the characteristic API spectrum. Since there are 2.75 anhydroglucose residues (AGU) for every iodine atom in the amylose–iodine (AI) complex and a structural similarity exists between the API and the AI (amylose–iodine) complexes, we identify (C₆H₁₀O₅)₁₁I₄ to be the chromophore in the API complex. © 1994 John Wiley & Sons, Inc.