Hussam A. Khatib

Light-Operated Mechanized Nanoparticles

Mesoporous silica (MCM-41) nanoparticles modified by azobenzene derivatives, capable of storing small molecules and releasing them following light irradiation, have been fabricated and characterized. In the presence of the beta-cyclodextrin and/or pyrene-modified beta-cyclodextrin rings, the beta-cyclodextrin and/or pyrene-modified beta-cyclodextrin rings will thread onto the azobenzene-containing stalks and bind to trans-azobenzene units to form the pseudorotaxanes, thus sealing the nanopores and stopping release of the cargo. Upon irradiation, the isomerization of trans-to-cis azobenzene units leads to the dissociation of the beta-cyclodextrin and/or pyrene-modified beta-cyclodextrin rings from the stalks, thus opening the gates to the nanopores and releasing the cargo.

pH Clock-Operated Mechanized Nanoparticles

Mechanized nanoparticles (MNPs) consisting of supramolecular machines attached to the surface of mesoporous silica nanoparticles are designed to release encapsulated guest molecules controllably under pH activation. The molecular machines are comprised of cucurbit[6]uril (CB[6]) rings that encircle tethered trisammonium stalks and can be tuned to respond under specific pH conditions through chemical modification of the stalks. Luminescence spectroscopy demonstrates that the MNPs are able to contain guest molecules within nanopores at neutral pH levels and then release them once the pH is lowered or raised.

Controlled-access hollow mechanized silica nanocontainers.

A new category of mechanized nanoparticles, consisting of a hollow mesoporous silica spherical framework controlled by a supramolecular system containing the alpha-cyclodextrin (alpha-CD) ring on a stalk that is tethered to the pore openings on the nanosphere, is synthesized and tested. Construction of the nanovalve relies on the hydrogen-bonding interaction between alpha-CD and the stalk. The stalk is bonded to the nanoparticle chemically and contains an anilino group that is located on the end of the linker molecule that is closest to the pore entrance. When the alpha-CD ring is complexed with the stalk at neutral pH, the bulky cyclic component is located near the pore openings, thereby blocking departure of cargo molecules that were loaded in the nanopores and hollow interior of the particle. Protonation of the nitrogen atoms at lower pH causes the binding affinity to decrease, releasing the alpha-CD and allowing the cargo molecules to escape. The properties of this newly designed pH-responsive nanovalve are compared to those of conventional mesoporous silica nanoparticles. The on-command pH-activated release is measured using luminescence spectroscopy. The effect of different stalk lengths and pH conditions on the release of fluorescent dye cargo molecules is measured.

Radically enhanced molecular recognition

The tendency for viologen radical cations to dimerize has been harnessed to establish a recognition motif based on their ability to form extremely strong inclusion complexes with cyclobis(paraquat-p-phenylene) in its diradical dicationic redox state. This previously unreported complex involving three bipyridinium cation radicals increases the versatility of host-guest chemistry, extending its practice beyond the traditional reliance on neutral and charged guests and hosts. In particular, transporting the concept of radical dimerization into the field of mechanically interlocked molecules introduces a higher level of control within molecular switches and machines. Herein, we report that bistable and tristable [2]rotaxanes can be switched by altering electrochemical potentials. In a tristable [2]rotaxane composed of a cyclobis(paraquat-p-phenylene) ring and a dumbbell with tetrathiafulvalene, dioxynaphthalene and bipyridinium recognition sites, the position of the ring can be switched. On oxidation, it moves from the tetrathiafulvalene to the dioxynaphthalene, and on reduction, to the bipyridinium radical cation, provided the ring is also reduced simultaneously to the diradical dication.

Snap-Top Nanocarriers

An approach to the design and fabrication of mechanized mesoporous silica nanoparticles is demonstrated at the proof of principle level. It relies on the reductive cleavage of disulfide bonds within an integrated nanosystem, wherein surface-bound rotaxanes incorporate disulfide bonds in their stalks, which are encircled by cucurbit[6]uril or alpha-cyclodextrin rings, until reductive chemistry is performed, resulting in the snapping of the stalks of the rotaxanes, leading to cargo release from the inside of the nanoparticles.

pH-Responsive mechanised nanoparticles gated by semirotaxanes

A [2]pseudorotaxane-based mechanised nanoparticle system, which operates within an aqueous acidic environment, has been prepared and characterised; this integrated system affords both water-soluble stalk and ring components in an effort to improve the biocompatibility of these promising new drug delivery vehicles.

Redox-driven switching in pseudorotaxanes

Two donor–acceptor thread-like compounds incorporating viologen (V2+) units and 1,5-dihydroxynaphthalene (DNP) stations have been prepared. Their ability to form self-assembled charge-transfer (CT) complexes with cucurbit[8]uril (CB[8]) is evidenced by UV-Vis and NMR spectroscopies, as well as by mass spectrometry. Binding studies show the formation of 1 : 1 and 2 : 1 complexes between CB[8] and a thread-like compound containing two viologen units, while only a 1 : 1 inclusion complex was observed between CB[8] and a thread-like compound containing only a single viologen unit. The switching behavior of the threads within their pseudorotaxane frameworks was investigated by using cyclic voltammetry (CV) and UV-Vis spectroscopy.

A tristable [2]pseudo[2]rotaxane

A strategy towards increasing the lifetime of the metastable state of a [2]rotaxane incorporating tetrathiafulvalene, 1,5-dioxynaphthalene and bipyridinium (BIPY(2+)) is presented. Incorporation of BIPY(2+) served multiple roles as an electrostatic barrier to relaxation, a supramolecular recognition site for bis-1,5-dioxynaphthalene[38]crown-10 macrocycle, and upon reduction a recognition site for the mechanically bonded cyclobis(paraquat-p-phenylene) ring.