Template-directed synthesis of multiply mechanically interlocked molecules under thermodynamic control

The template-directed construction of crown-ether-like macrocycles around secondary dialkylammonium ions (R2NH2+) has been utilized for the expedient (one-pot) and high-yielding synthesis of a diverse range of mechanically interlocked molecules. The clipping together of appropriately designed dialdehyde and diamine compounds around R2NH2+-containing dumbbell-shaped components proceeds through the formation, under thermodynamic control, of imine bonds. The reversible nature of this particular reaction confers the benefits of "error-checking" and "proof-reading", which one usually associates with supramolecular chemistry and strict self-assembly processes, upon these wholly molecular systems. Furthermore, these dynamic covalent syntheses exploit the efficient templating effects that the R2NH2+ ions exert on the macrocyclization of the matched dialdehyde and diamine fragments, resulting not only in rapid rates of reaction, but also affording near-quantitative conversion of starting materials into the desired interlocked products. Once assembled, these "dynamic" interlocked compounds can be "fixed" upon reduction of the reversible imine bonds (by using BH3.THF) to give kinetically stable species, a procedure that can be performed in the same reaction vessel as the inital thermodynamically controlled assembly. Isolation and purification of the mechanically interlocked products formed by using this protocol is relatively facile, as no column chromatography is required. Herein, we present the synthesis and characterization of 1) a [2]rotaxane, 2) a [3]rotaxane, 3) a branched [4]rotaxane, 4) a bis [2]rotaxane, and 5) a novel cyclic [4]rotaxane, demonstrating, in incrementally more complex systems, the efficacy of this one-pot strategy for the construction of interlocked molecules.     

Experimentally-based recommendations of density functionals for predicting properties in mechanically interlocked molecules

Mechanically interlocked molecules (rotaxanes and catenanes) have already revolutionized molecular electronics and have the promise of a similar impact in other areas of nanotechnology, ranging from nanoactuators to in vivo drug nanocarriers. However, it would be most useful to have quantitative criteria for predicting structures, binding, and excitation energies for use in designing molecules with mechanical bonds. We assess here the use of density functional theory (DFT) to a noncovalently bound complex and find that no density functional is fully satisfactory. However, we find that the new M06-suite of density functionals, which include attractive medium-range interactions, leads to dramatic improvements in the structures (error of 0.04 A in the interplanar distances for M06-L compared to 0.42 A for B3LYP) and excitation energies (within 0.08 eV for TD-M06-HF without empirical correction compared to 2.2 eV error for TD-B3LYP). However, M06 predicts the complex to be too strongly bound by 22.6 kcal mol(-1) (B3LYP leads to too weak a bond by 29 kcal mol(-1)), while current empirical FF DREIDING is too weakly bound by only 15 kcal mol(-1).     

Anion templated assembly of mechanically interlocked structures

This tutorial review describes the evolution of the field of chemical templation, in particular, emphasising the impact its application has made to the synthesis of mechanically interlocked structures. Recent advances in the use of negatively charged template species for the synthesis of interlocked structures are detailed, with the main focus of this review describing the development of a general anion templation strategy that combines anion recognition with ion-pairing. The versatility of this methodology is demonstrated by the chloride anion templated synthesis of a series of interpenetrated pseudorotaxane, rotaxane and catenane structures. Upon template removal, the mechanically interlocked rotaxanes and catenanes are shown to bind anions within their topologically unique anion binding clefts by virtue of electrostatic and hydrogen bonding interactions, exhibiting a strong selectivity for the chloride halide anion template. The incorporation of the photo-active rhenium(I) bipyridyl signalling group into the rotaxane structural framework highlights the potential of these interlocked systems in future chemical sensor design.     

Template-directed dynamic synthesis of mechanically interlocked dendrimers

The versatility and efficiency of dynamic covalent chemistry (DCC) has been exploited in the convergent synthesis of mechanically interlocked dendrimers that are based upon the mutual recognition expressed between secondary dialkylammonium ions and crown ether-like macrocycles. Reversible imine bond formation is employed to clip two acyclic fragments, one of them a diformylpyridine unit bearing a dendritic side chain, and the other a complementary dianiline in the shape of the di(o-aminophenyl)ether of tetraethylene glycol, around each arm of a tritopic trisammonium ion core, thereby affording a branched [4]rotaxane. This template-directed strategy has been demonstrated to work in very high yields (>90%) with successive generations (G0-G2) of a modified Fréchet-type dendritic wedge attached to the 4-position of the diformylpyridine unit. Reduction of these dynamic dendritic systems is achieved upon treatment with borane.THF and results in kinetically stable compounds. The inherent modularity of the overall process should allow for the rapid and straightforward access to many other analogous mechanically interlocked systems in which either the branched core or the dendritic periphery can be modified to suit the needs of any given application of these molecules. Indeed, the dynamic nature of the initial thermodynamically mediated assembly could be utilized in order to amplify particular products from a potential library as a result of a selective recognition process.     

Basic rules for the interpretation of atmospheric pressure ionization mass spectra of small molecules

This review summarizes the basic rules for the interpretation of atmospheric pressure ionization (API) mass spectra of small molecules written with the style primarily intended for beginners and low-experienced researchers with the mass spectra interpretation. The first and basic step in any interpretation of mass spectra is always the determination of molecular weight, which is relatively easy in case of soft ionization techniques due to the limited extend of fragmentation and the prevailing presence of (de)protonated molecules in the full scan mass spectra. These [M+H]⁺ and [M−H]⁻ ions are often accompanied by low abundant molecular adducts, which can be used as the supplementary information for the unambiguous determination of molecular weights. In certain cases, adduct ions may dominate the spectra. The subsequent interpretation of full scan and tandem mass spectra is more complicated due to a high number of possible functional groups, structural subunits and their combinations resulting in numerous competitive fragmentation pathways. Typical neutral losses and the effect of individual functional groups on the fragmentation are discussed in detail and illustrated with selected examples. Modern mass analyzers have powerful features for the structural elucidation, for example high resolving power, high mass accuracy, multistage tandem mass spectrometry, dedicated softwares for the interpretation of mass spectra and prediction of their fragmentation. Background information on differences among individual ionization techniques suitable for the HPLC–MS coupling and basic types of mass analyzers with consequences for the data interpretation is briefly discussed as well. Selected examples illustrate that the right optimization of chromatographic separation and the use of other than mass spectrometric detectors can bring valuable complementary information.     

EPR evidence of a triplet biradical in the photolysis of nifedipine

UV irradiation of nifedipine leads to of triplet biradicals that can be detected by means of EPR spectroscopy.     

Spin-labelled cyclodextrins as hosts for large supramolecular assemblies

EPR spectroscopy was used to study formation of inclusion complexes of monofunctionalised spin-labelled beta-cyclodextrins; this method is very sensitive to the interactions of cyclodextrins with large guest molecules.     

Real molecules as models for mathematical chemistry

A [2]-catenane consisting of methylene groups and two additional acetylated aza groups has been synthesized in a multi-step sequence. After splitting off the acetyl bonds, the resulting secondary diamine should provide a good starting material for stepreaction (condensation or addition, respectively) polymerization.     

Template-directed synthesis of mechanically interlocked molecular bundles using dynamic covalent chemistry

Mixing the dipyrido[24]crown-8 derivatives carrying one or two formyl group(s) on the 4 position(s) of their pyridine ring(s) with a 3-fold symmetrical trisammonium ion template in a 3:1 ratio in CD3NO2 results in the formation of thermodynamically stable [4]pseudorotaxanes which, upon addition of a 1,3,5-trisaminobenzene cap, form mechanically interlocked molecular bundles with one and two caps, respectively, by virtue of dynamic imine bond formation.     

High-frequency EPR spectra of

A detailed multifrequency high-field-high-frequency EPR (95-285 GHz) study has been performed on the single-molecule magnet of formula [Fe8O2(OH)12(tacn)6]Br8 x 9H2O, in which tacn = 1,4,7-triazacyclononane. Polycrystalline powder spectra have allowed the estimation of the zero-field splitting parameters up to fourth order terms. The single-crystal spectra have provided the principal directions of the magnetic anisotropy of the cluster. These results have been compared with an evaluation of the intra-cluster dipolar contribution to the magnetic anisotropy; this suggests that single-ion anisotropy is the main contributor to the magnetic anisotropy. The role of the transverse magnetic anisotropy in determining the height of the barrier for the reversal of the magnetization is also discussed.     

EPR breakup of polyatomic molecules

We explore the EPR experiment in the case of the breakup of a polyatomic molecule into two mutually entangled fragments. We give a derivation based on the properties of the dissociated wave function that no information is transferred, not even at a speed smaller than the speed of light, from one entangled partner to the other concerning its measurement or lack thereof. We also explain experiments that show that each separated fragment can retain coherences induced in its parent molecule by a broad band laser pulse, regardless of whether a measurement has been performed on its entangled partner.     

A mechanically interlocked molecular system programmed for the delivery of an anticancer drug

The development of mechanically interlocked molecular systems programmed to operate autonomously in biological environments is an emerging field of research with potential medicinal applications. Within this framework, functional rotaxane- and pseudorotaxane-based architectures are starting to attract interest for the delivery of anticancer drugs, with the ultimate goal to improve the efficiency of cancer chemotherapy. Here, we report an enzyme-sensitive [2]-rotaxane designed to release a potent anticancer drug within tumor cells. The molecular device includes a protective ring that prevents the premature liberation of the drug in plasma. However, once located inside cancer cells the [2]-rotaxane leads to the release of the drug through the controlled disassembly of the mechanically interlocked components, in response to a determined sequence of two distinct enzymatic activations. Furthermore, in vitro biological evaluations reveal that this biocompatible functional system exhibits a noticeable level of selectivity for cancer cells overexpressing β-galactosidase.     

Ring rotation of ferrocene in interlocked molecules in single crystals

This work describes unique molecular motions of ferrocene-containing interlocked molecules observed by single-crystal X-ray crystallography. The rotational flexibility of ferrocene is achieved using combinations of ferrocene-tethered ammonium and 30-membered ring dibenzo-crown ether. By contrast, ferrocene was locked in the complex with an 18-membered ring dibenzo-crown ether and CH₂Cl₂. When the complex was heated at 358 K, CH₂Cl₂ was removed from the complex, which led to drastic structural changes, including a semieclipsed-to-disordered transition of ferrocene and flipping of the dibenzo-crown ether.

Unique molecular motions, reversible internal rotation of ferrocene and flipping of crown ether are observed in DB30C10 and DB18C6-containing interlocked molecules, respectively.     

Hyperfine splitting in the ESR spectra of random oriented alkali earth biradical chelates

The ESR spectra of rigid glass solutions of biradicals of glyoxal diimine anions and alkali earth cations were recorded. The spectra could be computer simulated only by adding to the spin hamiltonian

= gβH·S + D[S_Z²?$\text{1}\text{2}$S(S+1)] a hyperfine term due to the anisotropic interaction of the nitrogen nuclei. Two different models were tested: the first one with the two radicals in the same plane and the second one with the two radicals perpendicular; agreement with the experiment was found for the latter.