Alexandra I. Lazar

Chemistry inside molecular containers in the gas phase

Inner-phase chemical reactions of guest molecules encapsulated in a macromolecular cavity give fundamental insight into the relative stabilization of transition states by the surrounding walls of the host, thereby modelling the situation of substrates in enzymatic binding pockets. Although in solution several examples of inner-phase reactions are known, the use of cucurbiturils as macrocyclic hosts and bicyclic azoalkanes as guests has now enabled a systematic mass spectrometric investigation of inner-phase reactions in the gas phase, where typically the supply of thermal energy results in dissociation of the supramolecular host-guest assembly. The results reveal a sensitive interplay in which attractive and repulsive van der Waals interactions between the differently sized hosts and guests need to be balanced with a constrictive binding to allow thermally activated chemical reactions to compete with dissociation. The results are important for the understanding of supramolecular reactivity and have implications for catalysis.

Broad-Spectrum Tunable Photoluminescent Nanomaterials Constructed from a Modular Light-Harvesting Platform Based on Macrocyclic Amphiphiles.

Broad-spectrum tunable photoluminescent nanomaterials are developed based on macrocyclic amphiphiles serving as a novel modular light-harvesting platform with discrete addressability of luminophores in a noncovalent way. By simply varying the donor/acceptor ratio, a broad spectrum of energy transfer outputs is achieved, pointing toward a proof-of-principle application as fluorescent inks for security printing.

A simple assay for quality binders to cucurbiturils.

A new approach towards the rapid identification of quality binders to cucurbiturils--those that combine high affinity with high selectivity for a particular homologue--was developed. The assay exploits macrocycle-specific optical fingerprints (colorimetric or fluorimetric) of carefully selected indicators dyes. The screening of a guest library revealed known (e.g., adamantane derivatives) and new (e.g., terpenes) quality binders. The predictive power of the assay was underpinned by the modeling of the involved thermodynamic equilibria.

Inclusion of neutral guests by water-soluble macrocyclic hosts – a comparative thermodynamic investigation with cyclodextrins, calixarenes and cucurbiturils

Abstract The driving forces of association between three different families of macrocycles as hosts, namely cyclodextrins (α-, β-, and γ-), p-sulfonatocalix[n]arenes (n = 4–6) as well as cucurbit[n]urils (n = 6–8), and three different bicyclic azoalkane homologues as guests, namely 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH), 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) as well as 2,3-diazabicyclo[2.2.3]non-2-ene (DBN), were examined by means of calorimetric titrations, NMR spectroscopy and molecular dynamics simulation, all in aqueous solution. The small, spherical and uncharged guests preferably bind inside the cavities of the medium sized hosts. The inclusion complexation by β-cyclodextrin and p-sulfonatocalix[4]arene shows medium binding affinities (millimolar), while cucurbit[7]uril macrocycle shows very strong binding (micromolar). For all types of macrocycles, the complex formation is enthalpically driven (ΔH° < 0), accompanied by slightly unfavourable entropy changes (ΔS° < 0). The results are discussed in terms of the flexibility of the hosts, the hydrophobic character of their cavities and the release of high-energy water upon binding, and generalised by including two additional guests, the ketones cyclopentanone and (+)-camphor.

Comparison of Complexation-Induced pKa Shifts in the Ground and Excited States of Dyes as Well as Different Macrocyclic Hosts and Their Manifestation in Host-Retarded Excited-Dye Deprotonation

1-Aminopyrene and 1-naphthylamine-5-sulfonic acid were converted to the putrescine (1,4-diaminobutane)-substituted derivatives (dyes 1 and 2). The diaminobutyl anchor serves as a common binding motive for cation-receptor macrocycles such as cucurbit[n]urils (n = 6-8) and p-sulfonatocalix[4]arene. When protonated, they are prone to undergo a rapid deprotonation in their excited state to result in fluorescence from the unprotonated form (Förster cycle). The deprotonation can be suppressed by complexation with cation-receptor macrocycles, which allows the fluorescence of the locally excited (protonated) state to be dramatically enhanced (factor 12 for dye 1 and 83 for dye 2). This host-retarded excited-dye deprotonation is a direct consequence of the previously established complexation-induced pKa shifts that dyes undergo upon binding to a macrocyclic host. The data set also allows a systematic comparison of complexation-induced pKa shifts in the ground and excited state of a dye. The trends are comparable, which suggests that structural factors, that is, the geometry of the host-guest complexes, determine the magnitude of the shifts. In regard to the magnitude of the absolute pKa shifts on the size of the macrocycles, we observe for dye 2 that the complexation-induced pKa shifts decrease as the portals become larger along the cucurbit[n]uril series.