Using the Photoluminescence Color Change in Cesium Lead Iodide Nanoparticles to Monitor the Kinetics of an External Organohalide Chemical Reaction by Halide Exchange.

In this work, we demonstrate a photoluminescence-based method to monitor the kinetics of an organohalide reaction by way of detecting released bromide ions at cesium lead halide nanoparticles. Small aliquots of the reaction are added to an assay with known concentrations of CsPbI3, and the resulting Br-to-I halide exchange (HE) results in rapid and sensitive wavelength blueshifts (Δλ) due to CsPbBrxI3-x intermediate concentrations, the wavelengths of which are proportional to concentrations. An assay response factor, C, relates Δλ to Br- concentration as a function of CsPbI3 concentration. The observed kinetics, as well as calculated rate constants, equilibrium, and activation energy of the solvolysis reaction tested correspond closely to synthetic literature values, validating the assay. Factors that influence the sensitivity and performance of the assay, such as CsPbI3 size, morphology, and concentration, are discussed.

Photoinduced Homolytic Bond Cleavage of the Central Si-C Bond in Porphyrin Macrocycles Is a Charge Polarization Driven Process.

Photoinduced cleavage of the bond between the central Si atom in porphyrin macrocycles and the neighboring carbon atom of an axial alkyl ligand is investigated by both experimental and computational tools. Photolysis and electron paramagnetic resonance measurements indicate that the Si-C bond cleavage of Si-phthalocyanine occurs through a homolytic process. The homolytic process follows a low-lying electronic excitation of about 1.8 eV that destabilizes the carbide bond of similar bond dissociation energy. Using electronic structure calculations, we provide insight into the nature of the excited state and the resulting photocleavage mechanism. We explain this process by finding that the electronic excited state is of a charge transfer character from the axial ligand toward the macrocycle in the reverse direction of the ground state polarization. We find that the homolytic process yielding the radical intermediate is energetically the most stable mechanistic route. Furthermore, we demonstrate using our computational approach that changing the phthalocyanine to smaller ring system enhances the homolytic photocleavage of the Si-C bond by reducing the energetic barrier in the relevant excited states.

Using Perovskite Nanoparticles as Halide Reservoirs in Catalysis and as Spectrochemical Probes of Ions in Solution.

The ability of cesium lead halide (CsPbX3; X = Cl(-), Br(-), I(-)) perovskite nanoparticles (P-NPs) to participate in halide exchange reactions, to catalyze Finkelstein organohalide substitution reactions, and to colorimetrically monitor chemical reactions and detect anions in real time is described. With the use of tetraoctylammonium halide salts as a starting point, halide exchange with the P-NPs was performed to calibrate reactivity, stability, and extent of ion exchange. The exchange of CsPbI3 with Cl(-) or Br(-) causes a significant blue-shift in absorption and photoluminescence, whereas reacting I(-) with CsPbBr3 causes a red-shift of similar magnitudes. With the high local halide concentrations and the facile nature of halide exchange in mind, we then explored the ability of P-NPs to catalyze organohalide exchange in Finkelstein like reactions. Results indicate that the P-NPs serve as excellent halide reservoirs for substitution of organohalides in nonpolar media, leading to not only different organohalide products, but also a complementary color change over the course of the reaction, which can be used to monitor kinetics in a precise manner. The merits of using P-NP as spectrochemical probes for real time assaying is then expanded to other anions which can react with, or result in unique, classes of perovskites.

Probing Bioluminescence Resonance Energy Transfer in Quantum Rod-Luciferase Nanoconjugates.

We describe the necessary design criteria to create highly efficient energy transfer conjugates containing luciferase enzymes derived from Photinus pyralis (Ppy) and semiconductor quantum rods (QRs) with rod-in-rod (r/r) microstructure. By fine-tuning the synthetic conditions, CdSe/CdS r/r-QRs were prepared with two different emission colors and three different aspect ratios (l/w) each. These were hybridized with blue, green, and red emitting Ppy, leading to a number of new BRET nanoconjugates. Measurements of the emission BRET ratio (BR) indicate that the resulting energy transfer is highly dependent on QR energy accepting properties, which include absorption, quantum yield, and optical anisotropy, as well as its morphological and topological properties, such as aspect ratio and defect concentration. The highest BR was found using r/r-QRs with lower l/w that were conjugated with red Ppy, which may be activating one of the anisotropic CdSe core energy levels. The role QR surface defects play on Ppy binding, and energy transfer was studied by growth of gold nanoparticles at the defects, which indicated that each QR set has different sites. The Ppy binding at those sites is suggested by the observed BRET red-shift as a function of Ppy-to-QR loading (L), where the lowest L results in highest efficiency and furthest shift.

Electrophoretic Interpretation of PEGylated NP Structure with and without Peripheral Charge.

Anchoring poly(ethylene glycol) (PEG) to inorganic nanoparticles (NPs) permits control over NP properties for a variety of technological applications. However, the core-shell structure tremendously complicates the interpretation of the ubiquitous ζ-potential, as furnished by electrophoretic light-scattering, capillary electrophoresis or gel electrophoresis. To advance the ζ-potential-and the more fundamental electrophoretic mobility-as a quantitative diagnostic for PEGylated NPs, we synthesized and characterized Au NPs bearing terminally anchored 5 kDa PEG ligands with univalent carboxymethyl end groups. Using the electrophoretic mobilities, acquired over a wide range of ionic strengths, we developed a theoretical model for the distributions of polymer segments, charge, electrostatic potential, and osmotic pressure that envelop the core: knowledge that will help to improve the performance of soft NPs in fundamental research and technological applications.

Functionalization of quantum rods with oligonucleotides for programmable assembly with DNA origami.

The DNA-mediated self-assembly of CdSe/CdS quantum rods (QRs) onto DNA origami is described. Two QR types with unique optical emission and high polarization were synthesized, and then functionalized with oligonucleotides (ssDNA) using a novel protection-deprotection approach, which harnessed ssDNA's tailorable rigidity and denaturation temperature to increase DNA coverage by reducing non-specific coordination and wrapping. The QR assembly was programmable, and occurred at two different assembly zones that had capture strands in parallel alignment. QRs with different optical properties were assembled, opening up future studies on orientation dependent QR FRET. The QR-origami conjugates could be purified via gel electrophoresis and sucrose gradient ultracentrifugation. Assembly yields, QR stoichiometry and orientation, as well as energy transfer implications were studied in light of QR distances, origami flexibility, and conditions.

Near infrared bioluminescence resonance energy transfer from firefly luciferase--quantum dot bionanoconjugates.

The bioluminescence resonance energy transfer (BRET) between firefly luciferase enzymes and semiconductive quantum dots (QDs) with near infrared emission is described. The QD were phase transferred to aqueous buffers using a histidine mediated phase transfer route, and incubated with a hexahistidine tagged, green emitting variant of firefly luciferase from Photinus pyralis (PPyGRTS). The PPyGRTS were bound to the QD interface via the hexahistidine tag, which effectively displaces the histidine layer and binds directly to the QD interfaces, allowing for short donor-acceptor distances (∼5.5 nm). Due to this, high BRET efficiency ratios of ∼5 were obtained. These PPyGRTS-QD bio-nano conjugates were characterized by transmission electron microscopy, thermal gravimetric analysis, Fourier transform infrared spectroscopy and BRET emission studies. The final optimized conjugate was easily observable by night vision imaging, demonstrating the potential of these materials in imaging and signaling/sensing applications.

Near infrared light-triggered drug generation and release from gold nanoparticle carriers for photodynamic therapy.

A photoprecursor Pc 227 is covalently bound onto gold nanoparticles (Au NPs) to produce the known photodynamic therapy (PDT) drug Pc 4 upon 660 nm photoirradiation. The photochemical formation of the photoproduct Pc 4 is identified by spectroscopy, chromatography, and mass spectrometry and its PDT efficacy is equal to Pc 4 when administered non-covalently by Au NPs, with the added benefit of improved covalent delivery and targeted NIR-triggered release from the covalent Pc 227-Au NP conjugate, while during transport the attached Pc 227 is quenched by the Au NP and PDT inactivated.

A method for separating PEGylated Au nanoparticle ensembles as a function of grafting density and core size.

After ligand exchange with PEG, Au NPs with differently mixed surface functionalities co-exist in the as-synthesized sample. It is found that the poorly grafted nanoparticles can be simply removed using a chromatographic method, and the well grafted nanoparticles can be eluted as a function of the core size.

Photophysics of silicon phthalocyanines in aqueous media.

Phthalocyanines have been used as photodynamic therapy (PDT) agents because of their uniquely favorable optical properties and high photostability. They have been shown to be highly successful for the treatment of cancer through efficient singlet-oxygen ((1)O(2)) production. However, due to their hydrophobic properties, the considerations of solubility and cellular location have made understanding their photophysics in vitro and in vivo difficult. Indeed, many quantitative assessments of PDT reagents are undertaken in purely organic solvents, presenting challenges for interpreting observations during practical application in vivo. With steady-state and time-resolved laser spectroscopy, we show that for axial ligated silicon phthalocyanines in aqueous media, both the water:lipophile ratio and the pH have drastic effects on their photophysics, and ultimately dictate their functionality as PDT drugs. We suggest that considering the presented photophysics for PDT drugs in aqueous solutions leads to guidelines for a next generation of even more potent PDT agents.

The unique role of nanoparticles in nanomedicine: imaging, drug delivery and therapy.

This critical review will present the role of nanoparticles (NPs) in the directions that are vital to the new field of nanomedicine, including imaging and drug delivery. We reflect on the physical properties that make NPs advantageous for in vivo efficacy, and review recent advances in major NP based biomedical applications. Critical questions of transport, uptake, and clearance will be discussed and illustrated through the success and opportunities of NP imaging and therapy on a photodynamic therapy (PDT) based NP system that has been developed in our lab over the past decade (540 references).

Nanoparticle ζ -potentials.

For over half a century, alternating electric fields have been used to induce particle transport, furnishing the ζ-potential of analytes with sizes ranging from a few nanometers to several micrometers. Concurrent advances in nanotechnology have provided new materials for catalysis, self-assembly, and biomedical applications, all of which benefit from a thorough understanding of particle surface charge. Therefore, the measurement of the ζ-potential via electrophoretic light scattering (ELS) has become essential for nanoparticle (NP) research. However, the interpretation of NP electrophoretic mobility, especially that of ligand-coated NPs, can be a complex undertaking. Despite the inherent intricacy of these data, key concepts from colloidal science can help to distill valuable information from ELS. In this Account, we adopt PEGylated Au NPs as an illustrative example to explore extensions of the classical theories of Smoluchowski, Hückel, and Henry to more contemporary theories for ligand-coated NP systems such as those from Ohshima, and Hill, Saville, and Russel. First, we review the basic experimental considerations necessary to understand NP electrophoretic mobility, identifying when O'Brien and White's numerical solution of the standard electrokinetic model should be adopted over Henry's closed-form analytical approximation. Next, we explore recent developments in the theory of ligand-coated particle electrophoresis, and how one can furnish accurate and meaningful relationships between measured NP mobility, ζ-potential, and surface charge. By identifying key ligand-coated NP parameters (e.g., coating thickness, permeability, molecular mass, and hydrodynamic segment size), we present a systematic method for quantitatively interpreting NP electrophoretic mobility. In addition to reviewing theoretical foundations, we describe our recent results that examine how the unique surface curvature of NPs alters and controls their properties. These data provide guidelines that can expedite the rational design of NPs for advanced uses, such as heterogeneous catalysis and in vivo drug delivery. As a practical demonstration of these concepts, we apply the ligand-coated theory to a recently developed noncovalent PEGylated Au NP drug-delivery system. Our analysis suggests that anion adsorption on the Au NP core may enhance the stability of these NP-drug conjugates in solution. In addition to providing useful nanochemistry insights, the information in this Account will be useful to biomedical and materials engineers, who use ELS and ζ-potentials for understanding NP dynamics.

Addressing brain tumors with targeted gold nanoparticles: a new gold standard for hydrophobic drug delivery?

EGF-modified Au NP-Pc 4 conjugates showed 10-fold improved selectivity to the brain tumor compared to untargeted conjugates. The hydrophobic photodynamic therapy drug Pc 4 can be delivered efficiently into glioma brain tumors by EGF peptide-targeted Au NPs. Compared to the untargeted conjugates, EGF-Au NP-Pc 4 conjugates showed 10-fold improved selectivity to the brain tumor. This delivery system holds promise for future delivery of a wider range of hydrophobic therapeutic drugs for the treatment of hard-to-reach cancers.

Measuring electron and hole transfer in core/shell nanoheterostructures.

Using femtosecond transient absorption and time-resolved photoluminescence spectroscopy, we studied the electron versus hole dynamics in photoexcited quasi-type-II heterostructured nanocrystals with fixed CdTe core radii and varying CdSe shell coverage. By choosing the pump wavelength in resonance with the core or the shell states, respectively, we were able to measure the excited electron and hole dynamics selectively. Both, the core- and the shell-excited CdTe/CdSe nanocrystals showed the same spectral emission and photoluminescence lifetimes, indicating that ultrafast electron and hole transfer across the core/shell interface resulted in the identical long-lived charge transfer state. Both charge carriers have subpicosecond transfer rates through the interface, but the subsequent relaxation rates of the hole (τ(dec) ∼ 800 ps) and electron (τ(avg) ∼ 8 ps) are extremely different. On the basis of the presented transient absorption measurements and fitting of the steady-state spectra, we find that the electron transfer occurs in the Marcus inverted region and mixing between the CdTe exciton and charge transfer states takes place and therefore needs to be considered in the analysis.

Electrophoretic mobilities of PEGylated gold NPs.

Electromigration of nanoparticles (NPs) is relevant to many technological and biological applications. We correlate the experimentally observed electromigration of Au NPs with a closed-form theoretical model that furnishes key NP characteristics, including the previously unknown values of Au NP core ζ-potential, PEG-corona permeability, and particle-hydrogel friction coefficient. More generally, the theory furnishes new understanding of NP electromigration in complex environments, establishing a robust and predictive model to guide the design and characterization of functionalized NPs.