The rupture forces of individual host-guest complexes between beta-cyclodextrin (beta-CD) heptathioether monolayers on Au(111) and several surface-confined guests were measured in aqueous medium by single molecule force spectroscopy using an atomic force microscope. Anilyl, toluidyl, tert-butylphenyl, and adamantylthiols (0.2-1%) were immobilized in mixed monolayers with 2-mercaptoethanol on gold-coated AFM tips. For all guests and for all surface coverages, the force-displacement curves measured between the functionalized tips and monolayers of beta-CD exhibited single, as well as multiple, pull-off events. The histograms of the pull-off forces showed several maxima at equidistant forces, with force quanta characteristic for each guest of 39 +/- 15, 45 +/- 15, 89 +/- 15, and 102 +/- 15 pN, respectively. These force quanta were independent of the loading rate, indicating that, because of the fast complexation/decomplexation kinetics, the rupture forces were probed under thermodynamic equilibrium. The force values followed the same trend as the free binding energy Delta G degrees measured for model guest compounds in solution or on beta-CD monolayers, as determined by microcalorimetry and surface plasmon resonance measurements, respectively. A descriptive model was developed to correlate quantitatively the pull-off force values with the Delta G degrees of the complexes, based on the evaluation of the energy potential landscape of tip-surface interaction.

Cyclodextrin derivatives modified with seven thioether moieties (1) or with one thiol moiety (2) bind to gold. Monolayers on gold of 1 or mixed monolayers of 2 and mercaptoundecanol were characterized by electrochemistry, wettability, and atomic force microscopy (AFM). Monolayers of 1 are well-ordered, but the order in the mixed monolayers depends on the ratio of 2 to mercaptoundecanol. With sufficient alkyl chains to fill the space under the cyclodextrin moiety of 2, the monolayers are densely packed. Guest recognition at these monolayers in water was studied by surface plasmon resonance (SPR) spectroscopy. For simple organic guests, monolayers of 1 showed the same selectivity and binding strength as beta-cyclodextrin in solution: however, the selectivity towards steroidal bile salts differs from solution. The mixed monolayers of 2, in which the cyclodextrin is less substituted and has more flexibility, bind steroidal guests (6a-6e) with the same selectivity as beta-cyclodextrin in solution.

We have developed synthesis routes for the introduction of short and long dialkylsulfides onto the primary side of a-, b-, and g-cyclodextrins. Monolayers of these cyclodextrin adsorbates were characterized by electrochemistry, wettability studies, X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (TOF-SIMS), and atomic force microscopy (AFM). The differences in thickness and polarity of the outerface of the monolayers were measured by electrochemistry and wettability studies. On average about 70 % of the sulfide moieties were used for binding to the gold, as measured by XPS. Tof-SIMS measurements showed that the cyclodextrin adsorbates adsorb without any bond breakage. AFM measurements revealed for b-cyclodextrin monolayers a quasihexagonal lattice with a lattice constant of 20.6 , which matches the geometrical size of the adsorbate. The a-cyclodextrin and g-cyclodextrin monolayers are less ordered. Interactions of the anionic guests 1-anilinonaphthalene-8sulfonic acid (1,8-ANS) and 2-(p-toluidinyl)naphthalene-6-sulfonic acid (2,6-TNS) and the highly ordered monolay-ers of heptapodant b-cyclodextrin adsorbates were studied by surface plasmon resonance (SPR) and electrochemical impedance spectroscopy. The SPR measurements clearly showed interactions between a b-cyclodextrin monolayer and 1,8-ANS. Electrochemical impedance spectroscopy measurements gave high responses even at low guest concentrations ( 5 mm). The association constant for the binding of 1,8-ANS (K 289 000 AE 13 000 m À1 ) is considerably higher than the corresponding value in solution. (Partial) methylation of the secondary side of the b-cyclodextrin strongly decreases the binding.

The dansyl-modified dimer 9 complexes strongly with the steroidal bile salts. Relative to native beta-cyclodextrin, the binding of cholate (1a) and deoxycholate (1b) salts is especially enhanced. These steroids bind exclusively in a 1:1 fashion. For other bile salts (1c-1e) both 1:1 and 1:2 complexes were observed with stabilities similar to those of native beta-cyclodextrin. This indicates that only one cavity is used, with a small contribution from the second. The difference is attributed to the absence of a 12-hydroxy group in the second group of steroids. Comparison with a dimer that lacks the dansyl moiety (6) shows that this group especially hinders the cooperative binding of la and 1b. The smaller interference in the binding of the other steroids indicates that self-inclusion of the dansyl moiety hardly occurs. This weak self-inclusion is supported by fluorescence studies. The dansyl fluorescence of dimer 9 is less blue-shifted than that of other known dansyl-appended cyclodextrin derivatives; this is indicative of a more polar micro-environment. Addition of guests causes a change in fluorescence intensity.