Measurement of the ground-state distributions in bistable mechanically interlocked molecules using slow scan rate cyclic voltammetry.

In donor-acceptor mechanically interlocked molecules that exhibit bistability, the relative populations of the translational isomers--present, for example, in a bistable [2]rotaxane, as well as in a couple of bistable [2]catenanes of the donor-acceptor vintage--can be elucidated by slow scan rate cyclic voltammetry. The practice of transitioning from a fast scan rate regime to a slow one permits the measurement of an intermediate redox couple that is a function of the equilibrium that exists between the two translational isomers in the case of all three mechanically interlocked molecules investigated. These intermediate redox potentials can be used to calculate the ground-state distribution constants, K. Whereas, (i) in the case of the bistable [2]rotaxane, composed of a dumbbell component containing π-electron-rich tetrathiafulvalene and dioxynaphthalene recognition sites for the ring component (namely, a tetracationic cyclophane, containing two π-electron-deficient bipyridinium units), a value for K of 10 ± 2 is calculated, (ii) in the case of the two bistable [2]catenanes--one containing a crown ether with tetrathiafulvalene and dioxynaphthalene recognition sites for the tetracationic cyclophane, and the other, tetrathiafulvalene and butadiyne recognition sites--the values for K are orders (one and three, respectively) of magnitude greater. This observation, which has also been probed by theoretical calculations, supports the hypothesis that the extra stability of one translational isomer over the other is because of the influence of the enforced side-on donor-acceptor interactions brought about by both π-electron-rich recognition sites being part of a macrocyclic polyether.

Isolation by crystallization of translational isomers of a bistable donor-acceptor [2]catenane.

The template-directed synthesis of a bistable donor-acceptor [2]catenane wherein both translational isomers--one in which a tetrathiafulvalene unit in a mechanically interlocked crown ether occupies the cavity of a cyclobis(paraquat-p-phenylene) ring and the other in which a 1,5-dioxynaphthalene unit in the crown ether resides inside the cavity of the tetracationic cyclophane--exist in equilibrium in solution, has led to the isolation and separation by hand picking of single crystals colored red and green, respectively. These two crystalline co-conformations have been characterized separately at both the molecular and supramolecular levels, and also by dynamic NMR spectroscopy in solution where there is compelling evidence that the mechanically interlocked molecules are present as a complex mixture of translational, configurational, and conformational isomers wherein the isomerization is best described as being a highly dynamic and adaptable phenomenon.

Anticancer activity expressed by a library of 2,9-diazaperopyrenium dications.

Polyaromatic compounds are well-known to intercalate DNA. Numerous anticancer chemotherapeutics have been developed upon the basis of this recognition motif. The compounds have been designed such that they interfere with the role of the topoisomerases, which control the topology of DNA during the cell-division cycle. Although many promising chemotherapeutics have been developed upon the basis of polyaromatic DNA intercalating systems, these candidates did not proceed past clinical trials on account of their dose-limiting toxicity. Herein, we discuss an alternative, water-soluble class of polyaromatic compounds, the 2,9-diazaperopyrenium dications, and report in vitro cell studies for a library of these dications. These investigations reveal that a number of 2,9-diazaperopyrenium dications show similar activities as doxorubicin toward a variety of cancer cell lines. Additionally, we report the solid-state structures of these dications, and we relate their tendency to aggregate in solution to their toxicity profiles. The addition of bulky substituents to these polyaromatic dications decreases their tendency to aggregate in solution. The derivative substituted with 2,6-diisopropylphenyl groups proved to be the most cytotoxic against the majority of the cell lines tested. In the solid state, the 2,6-diisopropylphenyl-functionalized derivative does not undergo π···π stacking, while in aqueous solution, dynamic light scattering reveals that this derivative forms very small (50-100 nm) aggregates, in contrast with the larger ones formed by dications with less bulky substituents. Alteration of the aromaticitiy in the terminal heterocycles of selected dications reveals a drastic change in the toxicity of these polyaromatic species toward specific cell lines.

Direct exfoliation of graphite to graphene in aqueous media with diazaperopyrenium dications.

The 2,9-dimethyldiazaperopyrenium dication can be made from a ubiquitous and inexpensive feedstock in three simple steps as its chloride salt. When mixed with powdered graphite at 23 °C, this behemoth of a molecular compound exfoliates graphite to graphene in water under mild conditions.

Dynamic covalent templated-synthesis of [c2]daisy chains.

A couple of [c2]daisy chains have been assembled in each case from four components in quantitative yields at room temperature in acetonitrile as a result of the self-templated clippings of their [24]crown-8 rings by reversible imine bond formation around secondary dialkylammonium recognition sites in their stalks.

Surface-Enhanced Raman Spectroelectrochemistry of TTF-Modified Self-Assembled Monolayers.

Surface-enhanced Raman spectroscopy (SERS) was used to monitor the response of a self-assembled monolayer (SAM) of a tetrathiafulvalene (TTF) derivative on a gold film-over-nanosphere electrode. The electrochemical response observed was rationalized in terms of the interactions between TTF moieties as the oxidation state was changed. Electrochemical oxidation to form the monocation caused the absorbance of the TTF unit to coincide with both the laser excitation wavelength and the localized surface plasmon resonance (LSPR), resulting in surface-enhanced resonance Raman scattering (SERRS). The vibrational frequency changes that accompany electron transfer afford a high-contrast mechanism that can be used to determine the oxidation state of the TTF unit in an unambiguous manner.

Multiple homeostatic mechanisms in the control of P1 plasmid replication.

Many organisms control initiation of DNA replication by limiting supply or activity of initiator proteins. In plasmids, such as P1, initiators are limited primarily by transcription and dimerization. However, the relevance of initiator limitation to plasmid copy number control has appeared doubtful, because initiator oversupply increases the copy number only marginally. Copy number control instead has been attributed to initiator-mediated plasmid pairing ("handcuffing"), because initiator mutations to handcuffing deficiency elevates the copy number significantly. Here, we present genetic evidence of a role for initiator limitation in plasmid copy number control by showing that autorepression-defective initiator mutants also can elevate the plasmid copy number. We further show, by quantitative modeling, that initiator dimerization is a homeostatic mechanism that dampens active monomer increase when the protein is oversupplied. This finding implies that oversupplied initiator proteins are largely dimeric, partly accounting for their limited ability to increase copy number. A combination of autorepression, dimerization, and handcuffing appears to account fully for control of P1 plasmid copy number.