Chiral Modification of Surfaces

This project is focused on the molecular-level study of heterogeneous catalytic processes for the manufacturing of chiral compounds of pharmaceutical interest.  Specifically, the adsorption of chiral modifiers is being investigating as a way to bestowing enantioselectivity to achiral surfaces.  Most of our studies up to date have been directed towards the characterization of the adsorption of cinchona alkaloids on platinum surfaces, both under vacuum and in-situ in solid-liquid interfaces [Z. Ma, I. Lee, J. Kubota and F. Zaera, J. Mol. Catal. A: Chem. 216 (2004) 199].  It has been determined from kinetic studies that heterogeneous hydrogenation catalysts such as platinum can be made enantioselective by the use of such molecular modifiers.  In particular, alpha-ketoesters such as ethyl pyruvate can be selectively hydrogenated by cinchona-modified platinum catalysts to produce the corresponding optically-pure (R)- or (S)-alpha-hydroxoesters (ethyl lactates from the pyruvate).  Our goal is to identify the underlying physical chemistry properties controlling that behavior.

The proposed mechanism by which the cinchona is believed to exert its effect is shown schematically below.  Three functional parts have been identified in these modifiers: (1) the anchoring quinoline aromatic ring, the moiety believed to be responsible for adsorption to the metal; (2) the tertiary quinuclidine ring, an amine group with a basic nitrogen atom which facilitates complexation with the reactant; and (3) the stereogenic region around the C8 and C9 carbon atoms responsible for the chirality of the product.  Each of these moieties appears to play a specific role in chiral catalysis.

The adsorption of cinchonidine from solution onto platinum surfaces is being probed in situ by reflection-absorption infrared spectroscopy (RAIRS). A proper assignment of the infrared absorption bands to specific vibrational normal modes of the molecule was first carried out by a combination of theoretical calculations and comparisons of vibrational spectra from a number of related compounds [W. Chu, R. J. LeBlanc, C. T. Williams, J. Kubota and F. Zaera, J. Phys Chem. B 107 (2003) 14365]; the spectra for cinchonidine adsorbed on platinum shown in the figure below was interpreted based on that work.  In general, in spite of the differences observed between the IR absorption traces for neat cinchonidine versus adsorbed on platinum, it was concluded that the room temperature adsorption of cinchonidine from solution is molecular.  Several tests were also performed to assure that the data correspond to cinchona monolayers and not to dissolved or condensed molecules [Z. Ma, I. Lee, J. Kubota and F. Zaera J. Mol. Catal. A: Chem. 216 (2004) 199].  The following was established: (1) The spectra obtained using p- and s-polarized light display the absorption anisotropy expected from adsorbed species.  (2) Spectra taken using different liquid film thickness do not show the increase in signal expected from dissolved species.  (3) The RAIRS spectra for surfaces saturated with cinchonidine persist even after flushing the system with fresh solvent, an observation that also points to the irreversibility of the adsorption (in carbon tetrachloride).  (4) No cinchona infrared peaks are detected on oxidized platinum surfaces; only on a surface cleaned by hydrogen pretreatments it is possible to see adsorbed cinchonidine.  (5) Repeated exposures of the surface to fresh cinchona-saturated solutions do not lead to the growth of the infrared absorption bands, as would be the case if they were due to physical condensation.

RAIRS data from platinum surfaces exposed to 0.5 (bottom) and 1.2 (miiddle) mM cinchonidine carbon tetrachloride solutions.  The spectrum of pure cinchonidine is provided at the top for reference.  The main peaks in these spectra were assigned by comparison of infrared and Raman data from analogous compounds as well as by ab-initio quantum-mechanic calculations.  It was determined that the data do indeed correspond to adsorbed (not dissolved) species, and that the adsorption is molecular.

Next, using the surface selection rule that applies to RAIRS for species adsorbed on metals, we were able to determine the orientation of the aromatic ring as the cinchonidine adsorbs on platinum substrates [J. Kubota and F. Zaera, J. Am. Chem. Soc. 123 (2001) 11115].  It was found that this geometry changes with coverage.  Specifically, three distinct adsorption regimes were identified for this system: (1) below 5%, where no discernible adsorption is detected in the spectra; (2) between 5 and 20%, at which point a few weak peaks are seen suggestive of a quinoline ring lying flat on the Pt surface; and (3) above 20%, which leads to the collective rearrangement to a tilted geometry.  What is particularly interesting is the excellent correlation that can be drawn between the different orientations of the species on the surface and the variations in activity and enantioselectivity during the chiral hydrogenation of keto esters previously reported in the literature, also illustrated in the figure below.  Maximum enantioselectivity is obtained at the concentrations where the modifier adopts the flat-lying adsorption geometry, that is, for cinchona-to-platinum atom ratios around 0.1.  It can be speculated that lower concentrations are not enough to provide sufficient modifier molecules on the surface for the chiral hydrogenation to proceed, while higher concentrations lead to surface crowding, forcing the aromatic ring to tilt on the surface and the catalyst to loose its enantioselective functionality.

Signal intensities for the infrared features at 1217 (filled circles) and 1512 cm-1 (filled squares) associated with flat and tilted adsorption geometries, respectively, as a function of cinchonidine concentration in a carbon tetrachloride solution.  The changes seen in these spectra correlate quite nicely with those reported for the activity and enantioselectivity of 10,11-dihydrocinchonidine-modified platinum towards the hydrogenation of ethyl pyruvate.

In general, it can be concluded from our research so far that the performance of the cinchona-modified platinum system is mainly defined by the characteristics of the adsorption of the modifier itself on the metal, and that those can be controlled by the conditions used in the catalytic process.  For one, optimal enantioselectivity appears to correlate with the concentration of the modifier, as discussed above.  Also, the catalyst needs to be pre-treated with hydrogen before the adsorption of the cinchona and the catalytic reaction can start [Z. Ma, J. Kubota and F. Zaera, J. Catal. 219 (2003) 404].  Lastly, both the cinchona adsorption and the activity and enantioselectivity of the cinchona/platinum system correlate well with the polar character of the solvent and with the solubility of the chiral modifier in it [Z. Ma and F. Zaera, J. Phys. Chem. B 109 (2005) 406].  Our next step is to determine the reasons behind the different adsorption geometries of these cinchona.  So far, our solution NMR and theoretical work suggest that the cinchona adsorption is defined by its molecular configuration, and that that can vary significantly upon seemingly small changes in the periphery of the molecular frame.  This hypothesis appears to indeed explain the difference in catalytic performance reported between the near enantiomers cinchonidine and cinchonine.  Our NMR studies suggest that the presence of the vinyl group closer to the quinoline ring in the latter restricts further rotations around the central C–C bonds, and therefore forces the molecules in a less stable configuration.

Structural details of the near enantiomers cinchonidine and cinchonine. Highlighted here is the fact that the vinyl group in the quinuclidine ring imposes rotational restrictions on the latter, blocking stable configurations available to the former.  These differences may be responsible for the differences seen in physical properties such as solubility, adsorption and catalysis.

Propylene oxide TPD (left) and RAIRS (right) data from titration experiments of 2-butoxide chiral layers with enantiopure propylene oxide.  The chiral 2-butoxide layers were prepared by dosing 0.4 L of either (R)- (bottom) or (S)- (top) 2-butanol on Pt(111) at 170 K.  For the TPD experiments, (S)-propylene oxide was then adsorbed at 100 K: the data indicate an increase of about 35% in (S)-propylene oxide uptake on the (S)-2-butoxide layer compared to the (R)-2-butoxide case.  In the RAIRS studies the 2-butoxide layers were dosed with 2.0 L of (R)-propylene oxide instead, but similar conclusions were reached.  Specifically, a number of differences were seen in the ring deformation region of the spectra: the peak at 822 cm-1 due to the monolayer is about five times more intense for the (R)-propylene oxide/(R)-2-butoxide case.