Abstract:The lessons learned from p-octiphenyl -barrel pores are applied to the rational design of synthetic multifunctional pore 1 that is unstable but inert, two characteristics proposed to be ideal for practical applications. Nonlinear dependence on monomer concentration provided direct evidence that pore 1 is tetrameric (n ) 4.0), unstable, and "invisible," i.e., incompatible with structural studies by conventional methods. The long lifetime of high-conductance single pores in planar bilayers demonstrated that rigid-rod -barrel 1 is inert and large (d ≈ 12 Å). Multifunctionality of rigid-rod -barrel 1 was confirmed by adaptable blockage of pore host 1 with representative guests in planar (8-hydroxy-1,3,6-pyrenetrisulfonate, KD ) 190 µM, n ) 4.9) and spherical bilayers (poly-L-glutamate, KD e 105 nM, n ) 1.0; adenosine triphosphate, KD ) 240 µM, n ) 2.0) and saturation kinetics for the esterolysis of a representative substrate (8-acetoxy-1,3,6-pyrenetrisulfonate, KM ) 0.6 µM). The thermodynamic instability of rigid-rod -barrel 1 provided unprecedented access to experimental evidence for supramolecular catalysis (n ) 3.7). Comparison of the obtained kcat ) 0.03 min -1 with the kcat ≈ 0.18 min -1 for stable analogues gave a global KD ≈ 39 µM 3 for supramolecular catalyst 1 with a monomer/barrel ratio ≈ 20 under experimental conditions. The demonstrated "invisibility" of supramolecular multifunctionality identified molecular modeling as an attractive method to secure otherwise elusive insights into structure. The first molecular mechanics modeling (MacroModel, MMFF94) of multifunctional rigid-rod -barrel pore hosts 1 with internal 1,3,6-pyrenetrisulfonate guests is reported.

This account summarizes five years of research devoted to the development of the concept of synthetic multifunctional pores. The objective is to complement a comprehensive graphical summary of molecular recognition with a survey of structural studies on the same topic. The relevance of the latter for research focusing on creation and application of supramolecular functional materials is discussed briefly in a subjective manner.

Dedicated to Professor Ulrich Burger on the occasion of his 65th birthdayThe usefulness of computer-assisted aliasing to secure maximal resolution of signal clusters in 1 H-and 13 C-NMR spectra (which is essential for structure determination by HMBC 2D NMR spectroscopy) in minimal acquisition time is exemplified by the complete characterization of the two complementary p-octiphenyls 1 and 2 with complex substitution patterns. The need for digital resolution near 1 Hz/pt to dissect the extensive signal clusters in the NMR spectra of these refined oligomers excluded structure determination under routine conditions. High resolution was secured by exploiting the low signal density in the 13 C dimension of HMBC spectra by using computer-assisted aliasing to maximize signal density. Based on the observed shifts in DEPT and 1 H-decoupled 13 C-NMR spectra of 1 and 2, computer-assisted aliasing allowed to reduce the number of required time increments by a factor of 20 to 30 compared to full-width spectra with identical resolution. Without signal-to-noise constraints, this computer-assisted aliasing reduced the acquisition time for highresolution NMR spectra needed for complete characterization of refined oligomers 1 and 2 by the same factor (e.g., from over a day to about an hour). With resolved signal clusters in fully aliased HSQC and HMBC spectra, unproblematic structure determination of 1 and 2 is demonstrated by unambiguous assignment of all C-and Hatoms. These findings demonstrate that computer-assisted aliasing of the underexploited 13 C dimension makes extensive molecular complexity accessible by conventional multidimensional heteronuclear NMR experiments without extraordinary efforts.

The objective of this paper is to clarify a frequent confusion that occurs with synthetic multifunctional pores: does molecular recognition by a synthetic pore exclude molecular translocation through the same pore? Evidence that this is not the case is provided with a set of competitive experiments using a rigid‐rod β‐barrel with internal histidine–arginine dyads as synthetic multifunctional pores (SMPs) as well as 8‐hydroxypyrene‐1,3,6‐trisulfonate (HPTS) as a fluorescent and 1,3,6,8‐pyrenetetrasulfonate (PTS) as a non‐fluorescent blocker. Direct evidence for the efflux of HPTS blockers through blocked SMPs is obtained by quenching of released HPTS with an externally added quencher. Blockage of blocker efflux through blocked pores was demonstrated by adding PTS as the opposing external blocker (KD = 3.3 μM). A Hill coefficient of n = 1.5 may indicate that binding of more than one PTS blocker is necessary to inhibit the efflux of HPTS blockers. Supported by structural information on blockage and selectivity from biological potassium channels, blocker efflux through blocked pores is discussed as being implicated in selectivity. Copyright © 2004 John Wiley & Sons, Ltd.

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