Dermot F. Brougham

Nanoparticle clusters: assembly and control over internal order, current capabilities and future potential

The current state of the art in the use of colloidal methods to form nanoparticle assemblies, or clusters (NPCs) is reviewed. The focus is on the two-step approach, which exploits the advantages of bottom-up wet chemical NP synthesis procedures, with subsequent colloidal destabilization to trigger assembly in a controlled manner. Recent successes in the application of functional NPCs with enhanced emergent collective properties for a wide range of applications, including in biomedical detection, surface enhanced Raman scattering (SERS) enhancement, photocatalysis, and light harvesting, are highlighted. The role of the NP-NP interactions in the formation of monodisperse ordered clusters is described and the different assembly processes from a wide range of literature sources are classified according to the nature of the perturbation from the initial equilibrium state (dispersed NPs). Finally, the future for the field and the anticipated role of computational approaches in developing next-generation functional NPCs are briefly discussed.

Polypeptides by light: photo-polymerization of N-carboxyanhydrides (NCA)

The synthesis of polypeptides by N-carboxyanhydride (NCA) photopolymerization is demonstrated. The active initiator cyclohexylamine was produced in situ by the UV-induced breakdown of photoamine generators. Real-time FTIR and MALDI-ToF-MS analyses provide clear evidence for the proposed photoinitiation mechanism as well as the attachment of the active initiator to the polypeptide chain. NCA photopolymerization generates new possibilities for designing polypeptides both in solution and on surfaces.

Investigation of the triazolinedione (TAD) reaction with tryptophan as a direct route to copolypeptide conjugation and cross-linking

The reaction of tryptophan containing N-carboxyanhydride (NCA) derived polypeptides with triazolinedione (TAD) is demonstrated. This click-like reaction is fast, selective and permits polypeptide conjugation utilising a natural amino acid. It thereby omits the need for synthesis of non-natural amino acid derivatives or protection/deprotection strategies. Its feasibility is demonstrated for the synthesis of polypeptide gels and films using difunctional TAD derivatives such as novel PEG-bis-TAD.

Exploring Tyrosine‐Triazolinedione (TAD) Reactions for the Selective Conjugation and Cross‐Linking of N‐Carboxyanhydride (NCA) Derived Synthetic Copolypeptides

Highly efficient functionalization and cross-linking of polypeptides is achieved via tyrosine-triazolinedione (TAD) conjugation chemistry. The feasibility of the reaction is demonstrated by the reaction of 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) with tyrosine containing block copolymer poly(ethylene glycol)-Tyr4 as well as a statistical copolymer of tyrosine and lysine (poly(Lys40 -st-Tyr10 )) prepared form N-carboxyanhydride polymerization. Selective reaction of PTAD with the tyrosine units is obtained and verified by size exclusion chromatography and NMR spectroscopy. Moreover, two monofunctional and two difunctional TAD molecules are synthesized. It is found that their stability in the aqueous reaction media significantly varied. Under optimized reaction conditions selective functionalization and cross-linking, yielding polypeptide hydrogels, can be achieved. TAD-mediated conjugation can offer an interesting addition in the toolbox of selective (click-like) polypeptide conjugation methodologies as it does not require functional non-natural amino acids.

Size selectable nanoparticle assemblies with magnetic anisotropy tunable across the superparamagnetic to ferromagnetic range

We present a novel approach for the preparation of magnetic nanoparticle clusters of controlled size and selectable magnetic anisotropy, which provides materials with properties selectable for biomedical applications and as components in magnetically responsive nanocomposites. The assembly process is based on a ligand desorption strategy and allows selection of nanoparticle size and temporal control over final cluster size. Detailed NMR analysis of the suspensions pinpoints the role of particle size in controlling the interparticle interactions, within the clusters, which effectively determine the anisotropy. Colloidal interaction modelling confirms this interpretation and provides a means to predict both colloidal stability and magnetic anisotropy.

Polypeptide polymer brushes by light-induced surface polymerization of amino acid N-carboxyanhydrides

Silicon wafers are decorated with photoamine generator 4,5-dimethoxy-2-nitrobenzyl 3-(triethoxysilyl)propyl carbamate. UV-irradiation in the presence of benzyl-l-glutamate N-carboxyanhydride is carried out, resulting in the release of the surface-bound primary amines, making them viable N-carboxyanhydride (NCA) polymerization initiators. Successful polypeptide grafting is confirmed by water contact angle measurements as well as by ellipsometry, revealing a poly(benzyl-l-glutamate) (PBLG) layer of ≈3 nm. X-ray photoelectron spectroscopy confirms the presence of amide groups in the grafted PBLG while time-of-flight secondary ion mass spectroscopy provides additional evidence for the presence of PBLG on the surface. Evaluation of negative control samples confirms successful UV surface grafting. The approach is thus established as a viable general method for light exposure directable polypeptide functionalization of silicon surfaces.

Aggregation kinetics and cluster structure of amino-PEG covered gold nanoparticles

In this study controlled clustering kinetics is demonstrated for PEG grafted gold nanoparticles, in response to applied environmental stimuli; the temperature and ionic strength of the medium. It is also found that the rate of assembly determines the structure of the prepared clusters. After the system is brought out of equilibrium, time-dependent extinction and dynamic light scattering data are used to follow the evolution of nanoparticle cluster formation in real time. The results show that the rate of assembly increases with increasing ionic strength or temperature of the medium. As a result the nanoparticle cluster size scales with ionic strength and temperature, over a cluster size range from a few particle sizes up to the micron-scale. It is found that, even at the lowest ionic strength, the electric double layer repulsion is eliminated; hence the observed differences in kinetics and in cluster structure arise from modulation of the repulsive steric interactions between nanoparticles. The approach should be extendable to suspensions of other nanoparticle types, where the nanoparticle stability is determined by surface-grafted responsive macromolecules.

Glyco-copolypeptide grafted magnetic nanoparticles: the interplay between particle dispersion and RNA loading

Lysine-glyco-copolypeptide grafted superparamagnetic iron oxide nanoparticles were prepared through N-carboxyanhydride (NCA) copolymerization. Statistical and block copolymer arrangements were obtained while keeping the overall composition constant. Both type of nanoparticles are fully water dispersible, which is key for T1-weighted magnetic resonance imaging (MRI) applications. A synergistic effect between siRNA loading and imaging properties was observed in the statistical copolymer arrangement allowed a significantly higher loading while retaining full particle dispersion, as required for T1-weighting.

Nanoparticle Assemblies: Nanoparticle Clusters: Assembly and Control Over Internal Order, Current Capabilities, and Future Potential (Adv. Mater. 27/2016)

Clusters or assemblies of nanoparticles exhibit unique features which arise from the enhancement of properties of single nanoparticles or due to new collective properties. On page 5400, D. F. Brougham and co-workers review the role of nanoparticle interactions in controlling cluster formation, and classify the assembly mechanisms. Emerging applications for surface-enhanced Raman scattering (SERS), optical labeling, light harvesting, magnetic resonance imaging (MRI), hyperthermia, photocatalysis, enrichment, and separation are presented. Cover image by Christoph Hohmann, Nanosystems Initiative Munich (NIM).

Size-Controlled Nanoparticle Clusters of Narrow Size-Polydispersity Formed Using Multiple Particle Types Through Competitive Stabilizer Desorption to a Liquid-Liquid Interface

A novel colloidal approach is presented for preparing fully dispersed nanoparticle (NP) assemblies (clusters) of narrow size-polydispersity over a wide range of sizes through irreversible depletion of stabilizing ligands onto a liquid-liquid interface. Unusually, the relative monodispersity of the assemblies continuously improves throughout the process. A detailed kinetics study into the assembly of iron oxide NP clusters shows that the assembly rate decreases with NP concentration, pinpointing the role of the interface in size focusing. A new protocol for identifying initial conditions that enable controlled assembly is described, which allows extension of the approach to multiple NP types, opening up a general route to colloidally processed materials. The process uses cheap materials, it is reproducible, robust, and scaleable, and it allows for selection of both particle and cluster size. In the case of assemblies of magnetic iron oxide NPs, these advantages enable tuning of the magnetic properties of the assemblies for applications such as magnetically targetable MRI-trackable agents in biomedicine.