Henk H. Dam

Multicoordinate ligands for actinide/lanthanide separations

In nuclear waste treatment processes there is a need for improved ligands for the separation of actinides (An(III)) and lanthanides (Ln(III)). Several research groups are involved in the design and synthesis of new An(III) ligands and in the confinement of these and existing An(III) ligands onto molecular platforms giving multicoordinate ligands. The preorganization of ligands considerably improves the An(III) extraction properties, which are largely dependent on the solubility and rigidity of the platform. This tutorial review summarizes the most important An(III) ligands with emphasis on the preorganization strategy using (macrocyclic) platforms.

Targeting of Cancer Cells Using Click-Functionalized Polymer Capsules

Targeted delivery of drugs to specific cells allows a high therapeutic dose to be delivered to the target site with minimal harmful side effects. Combining targeting molecules with nanoengineered drug carriers, such as polymer capsules, micelles and polymersomes, has significant potential to improve the therapeutic delivery and index of a range of drugs. We present a general approach for functionalization of low-fouling, nanoengineered polymer capsules with antibodies using click chemistry. We demonstrate that antibody (Ab)-functionalized capsules specifically bind to colorectal cancer cells even when the target cells constitute less than 0.1% of the total cell population. This precise targeting offers promise for drug delivery applications.

The role of solvent vapor annealing in highly efficient air-processed small molecule solar cells

We demonstrate highly-efficient, solution-processed small molecule solar cells with the best power conversion efficiency (PCE) of more than 5%. The active layer consists of a diketopyrrolopyrrole-based donor molecule (DPP(TBFu)2) and a fullerene derivative (PC71BM) that is spin cast and subsequently treated with solvent vapor annealing (SVA) in air. We find not all solvent vapors lead to the best PCE. Solvents of high vapor pressures and medium donor solubilities, such as tetrahydrofuran or carbon disulfide, are most suitable for SVA in the context of organic solar cell application. On the other hand, acceptor solubility plays an insignificant role in such a treatment. An active layer treated with ideal solvent vapors develops desirable phase separation in both lateral and vertical directions, as revealed by AFM, TEM and TEM tomography. The SVA also leads to enhanced hole mobility. We believe the fast SVA treatment performed in air is a viable way to tune the active layer morphology for printed solar cells.

Gradient-driven motion of multivalent ligand molecules along a surface functionalized with multiple receptors

The kinetics of multivalent (multisite) interactions at interfaces is poorly understood, despite its fundamental importance for molecular or biomolecular motion and molecular recognition events at biological interfaces. Here, we use fluorescence microscopy to monitor the spreading of mono-, di- and trivalent ligand molecules on a receptor-functionalized surface, and perform multiscale computer simulations to understand the surface diffusion mechanisms. Analogous to chemotaxis, we found that the spreading is directional (along a developing gradient of vacant receptor sites) and is strongly dependent on ligand valency and concentration of a competing monovalent receptor in solution. We identify multiple surface diffusion mechanisms, which we call walking, hopping and flying. The study shows that the interfacial behaviour of multivalent systems is much more complex than that of monovalent ones.

Probing Multivalent Interactions in a Synthetic Host–Guest Complex by Dynamic Force Spectroscopy

Multivalency is present in many biological and synthetic systems. Successful application of multivalency depends on a correct understanding of the thermodynamics and kinetics of this phenomenon. In this Article, we address the stability and strength of multivalent bonds with force spectroscopy techniques employing a synthetic adamantane/β-cyclodextrin model system. Comparing the experimental findings to theoretical predictions for the rupture force and the kinetic off-rate, we find that when the valency of the complex is increased from mono- to di- to trivalent, there is a transition from quasi-equilibrium, with a constant rupture force of 99 pN, to a kinetically dependent state, with loading-rate-dependent rupture forces from 140 to 184 pN (divalent) and 175 to 210 pN (trivalent). Additional binding geometries, parallel monovalent ruptures, single-bound divalent ruptures, and single- and double-bound trivalent ruptures are identified. The experimental kinetic off-rates of the multivalent complexes show that the stability of the complexes is significantly enhanced with the number of bonds, in agreement with the predictions of a noncooperative multivalent model.

Construction and Degradation of Polyrotaxane Multilayers

4 Polyrotaxanes (PRXs) [ 1 ] consisting of linear poly(ethylene glycol) (PEG) and multiple threaded α -cyclodextrins ( α CD) [ 2 ] exhibit a number of intriguing and tunable properties. [ 3 , 4 ] An illustrative example is the improved multivalent binding of threaded α CDs to ligands, which is a direct result of the rotational freedom and sliding mobility experienced by the α CDs in these PRXs. [ 5 ]

Mechanics of pH-Responsive Hydrogel Capsules

While soft hydrogel nano- and microstructures hold great potential for therapeutic treatments and in vivo applications, their nanomechanical characterization remains a challenge. In this paper, soft, single-component, supported hydrogel films were fabricated using pendant-thiol-modified poly(methacrylic acid) (PMASH). The influence of hydrogel architecture on deformation properties was studied by fabricating films on particle supports and producing free-standing capsules. The influence of the degree of thiol-based cross-linking on the mechanical properties of the soft hydrogel systems (core-shell and capsules) was studied using a colloidal-probe (CP) AFM technique. It was found that film mechanical properties, stability, and capsule swelling could be finely tuned by controlling the extent of poly(methacrylic acid) thiol modification. Furthermore, switching the pH from 7.4 to 4.0 led to film densification due to increased hydrogen bonding. Hydrogel capsule systems were found to have stiffness values ranging from 0.9 to 16.9 mN m(-1) over a thiol modification range of 5 to 20 mol %. These values are significantly greater than those for previously reported PMASH planar films of 0.7-5.7 mN m(-1) over the same thiol modification range (Best et al., Soft Matter 2013, 9, 4580-4584). Films on particle substrates had comparable mechanical properties to planar films, demonstrating that while substrate geometry has a negligible effect, membrane and tension effects may play an important role in capsule force resistance. Further, when transitioning from solid-supported films to free-standing capsules, simple predictions of shell stiffness based on modulus changes found for supported films are not valid. Rather, additional effects like diameter increases (geometrical changes) as well as tension buildup need to be taken into account. These results are important for research related to the characterization of soft hydrogel materials and control over their mechanical properties.

Formation and degradation of layer-by-layer-assembled polyelectrolyte polyrotaxane capsules.

We report the preparation of degradable capsules via layer-by-layer assembly using polyelectrolyte (PE) polyrotaxanes (PRXs). The PRX capsules were prepared by the sequential deposition of PRXs onto silica particles followed by the dissolution of the silica cores. The colloidal stability of the PRX capsules that are formed depends on the salt/buffer solution used in the assembly process. Various salt/buffer combinations were examined to avoid aggregation of the core-shell particles during PRX assembly and core dissolution. Using appropriate assembly conditions, we prepared colloidally stable, robust capsules. PRX capsules consisting of eight layers of PE PRXs had a wall thickness of ~15 nm. The degradation of the PRX capsules was demonstrated through the disassembly of the PE PRXs using glutathione, which cleaves the disulfide bonds linking the end-capping groups of the PE PRXs. Given the supramolecular noncovalent structure of PRXs and their adjustable properties, it is expected that PRXs will be used as building blocks for assembling advanced capsules with unique and tailored properties.

Influence of the platform in multicoordinate ligands for actinide partitioning

Multicoordinate ligands based on the trityl, C-pivot, and CTV platforms and the ligating groups CMPO, DGA, PICO, and MPMA were synthesized and studied for their extraction properties. The extraction efficiencies of these multicoordinate ligands are largely influenced by the properties of the platform. The DAm values follow the order CTV6 > trityl ≈ C-pivot > CTV3 > CTV0 with a maximum for CTV6CMPO of DAm = 30 (SAm/Eu = 1.4, cL = 10–4 M, 3 M HNO3). There is a strong relationship between the DAm values, increasing in the order of CTV0CMPO < CTV3CMPO < CTV6CMPO, and the ‘mobility’ of their CMPO groups. The SAm/Eu values are less influenced by the platform and range between 0.2 and 2.0, though they can reverse under the influence of the HNO3 concentration (CTV6PICOSAm/Eu = 0.7 at 0.001 M HNO3 to 1.2 at 0.01 M HNO3) or by changing the platform (CTV(0, 3 or 6)MPMA from SAm/Eu = 0.4 to 1.6 for tritMPMA both at 0.001 M HNO3). For the CMPO derivatives the SAm/Eu values are most consistent, ranging from 1.4 to 1.8.

Modular click assembly of degradable capsules using polyrotaxanes.

A modular approach for the formation of degradable capsules using polyrotaxanes (PRXs) is described. The PRXs consist of α-cyclodextrin (αCD) and poly(ethylene glycol) (PEG), which are both biologically benign and the main degradation products of the capsules. The PRXs were equipped with three alkyne groups at their ends and could be successfully grafted to azide-functionalized silica particles (2.76 μm diameter) using azide-alkyne click chemistry. The assembled PRXs were then cross-linked using a degradable linker. The cross-linked structure was sufficiently robust to allow the formation of capsules after dissolving the template silica particles. The formation of capsules of ca. 2 μm diameter was verified by optical microscopy, TEM, and AFM imaging. The capsules were loaded with the chemotherapy drug doxorubicin (DOX) by conjugating it to the threaded αCDs via their free OH groups, while maintaining degradability of the capsules. Alkyne moieties at the surface of the cross-linked PRX architecture were available for further functionalization of the capsules, as is demonstrated by clicking on fluorescent PEG moieties. The DOX-loaded capsules were degraded within 90 min at 37 °C upon exposure to a 5 mM solution of glutathione in water.