Peter Forgo

Selective modification at the 3-position of β-cyclodextrin

Abstract Heptakis(6- O - tert -butyldimethylsilyl) β -cyclodextrin reacts with N -methyl-4-chloromethyl-2-nitroaniline to produce the 3-modified cyclodextrin after the necessary deprotection step. Complete NMR assignment and its comparison with cyclodextrin derivatives modified by the same group at the 2- and 6-position is reported.

Structure and electrochemical behavior of a flavin sulfide monolayer adsorbed on gold

The electrochemical behavior and structure of monolayers of the synthetic flavin 10-(3′-methylthiopropyl)-isoalloxazinyl-7-carboxylic acid adsorbed on gold is reported. The redox behavior of the compound is quasi-reversible. The surface concentration is estimated to be 1.5×10−10 mol cm−2. An electron transfer rate constant of 340 s−1 is estimated for the cathodic process and a value of 540 s−1 is estimated for the anodic process. The reduction potential of the monolayer is found to shift with pH as expected for a 2e−, 2H+ process. The monolayers have also been characterized by X-ray photoelectron spectroscopy (XPS) and low voltage field emission secondary electron microscopy (LVFESEM). The most likely orientation would have the long axis parallel to the surface with the carboxyl group exposed to the solution. A comparison of the C1s XPS spectra at glancing and normal emission indicates that the carboxyl group is at the film surface. The LVFESEM images indicate that the molecules pack in domains that do not follow the topology of the gold grains. Semi-quantitative examination of the micrographs shows that 10–15% of the gold surface is uncovered. The bare gold substrate catalyzes the oxidation of NADH; the presence of the flavin film reduces the observed catalysis by the gold substrate.

Electrochemical study of self-assembled monolayers of a β-cyclodextrin methyl sulfide covalently linked to anthraquinone

Abstract Self-assembled monolayers of a β-cyclodextrin with methyl sulfides on the primary sites of the molecule and mono-functionalized with anthraquinone on a secondary site have been formed on gold electrodes. The surface coverages obtained by electrochemistry are consistent with values reported previously or calculated for similar non-electroactive β-CD derivatives. The electron transfer rate constants vary markedly with pH, increasing rapidly between pH 7 and 9 to values of approximately 700–900 s−1. These values are faster than reported previously for thiol derivatives of anthraquinone dispersed in an alkylthiol SAM matrix. Near pH 6, slow electron transfer is observed with a splitting into individual one-electron steps. Lowering the pH further results in very sluggish kinetics and indistinguishable peaks. Inclusion of naphthalene into the β-CD cavity appears to affect the anodic rate constant, and a small potential shift occurs. The efficient electron transfer of the anthraquinone spaced from the gold surface by a β-CD unit suggests promise for use of such molecules as ‘immobilized artificial enzymes’.

An NMR approach for the determination of the substitution pattern in mono-modified cyclodextrins

Abstract One of the problems in cyclodextrin chemistry is the unequivocal determination of structures of systems under investigation. A simple procedure that can be used for the determination of the position of the substitution in these systems is presented here. The main requirement of this procedure is that the proton attached to the substituted carbon has a magnetic environment that is different from other likely sites of attachment.

Determination of proton-proton distances in 2-acetamido-2-deoxy monosaccharides from 1H NMR relaxation measurements in solution

Abstract Determination of selective and biselective 1 H spin-lattice relaxation rates combined with steady-state and transient 1 H 1 H NOE data allowed calculation of intramolecular proton-proton distances in 2-acetamido-2-deoxy- d -glucosides ( 1a an 1b ), 2-acetamido-2-deoxy- d -mannoses ( 5a and 5b ) and their acetylated derivatives. These measurements were supplemented by DESERT studies using derivatives selectively labeled by 2 H at position 2. These distance data are in good correlation with literature values obtained by X-ray crystallography. Interproton distance measurements allow the determination of relative configurations, including that of the anomeric carbon, in hexopyranose rings in cases where other methods, like those based on scalar coupling constants, fail.

High-field NMR studies of 3β-tetrahydropyranyloxy steroids

Abstract Comprehensive NMR studies were carried out on 3β-hydroxy-pregnene and cholestene analogs, each containing a tetrahydropyranyl ether group at the 3-position. Two-dimensional NMR experiments (COSY, TOCSY, HSQC, and HSQC-TOCSY) permitted the complete assignments of both the 1H and 13C resonances of these derivatives in deuterated benzene or chloroform. The aromatic solvent-induced NMR signal shifts (ASIS) were also investigated.

Application of a selective HSQC experiment to measure interglycosidic heteronuclear long-range coupling constants in cyclodextrins

A selective one‐dimensional HSQC experiment was used to obtain heteronuclear long‐range coupling constants for native and chemically modified cyclodextrins (3,6‐anhydro‐β‐cyclodextrin) and a non‐covalent complex of α‐cyclodextrin with p‐nitrophenol. Selective excitation was performed on C‐4 in the α‐glucose units using DANTE hard pulse trains. The measured heteronuclear long‐range coupling constants have similar values for all natural cyclodextrins. The high value of these coupling constants indicates that the low dihedral angle between H‐1 and C‐4 found in the solid state is retained in solution. Chemical modification or complex formation, however, decreases the coupling constant by increasing the dihedral angle between these nuclei.

Selective Modifications of Cyclodextrins

It is indeed a pleasure and an honor to present this talk at the beautiful and ancient city of Santiago de Compostela and I would like to thank the organizers for giving me an opportunity to do so. We all love cyclodextrins and we like to study them, use them, play with them and even make some money out of them. The question is, if they are so incredible molecules, why do we need to change them? The answer is that in spite of their extraordinary properties, limitations of available functional groups and rigidity of their structure restrict our ability to utilize them. A number of very prominent chemists have attempted to rectify this situation and have provided us with methods to modify them.1 In this talk, I will present our contribution to this effort. I will first introduce the chemistry involved in selective modification of cyclodextrin, then I will discuss mono-modification of cyclodextrins in which we have attached the same group (4-methylamino-3-nitro-benzyl group) selectively at the 2-, 3- and the 6-positions. I will then present our contribution in per-modification of cyclodextrins.