Revealing the Existence of Long-Range Liquid-Liquid Interfacial Potential in Phase-Transfer Processes.

By employing fluorescence wide-field microscopy and a nanoparticle-based phase transfer catalyst (PTC), consisting of a fluorescent silica nanoparticle functionalized with trioctylpropylammonium bromide, we demonstrate that in the presence of NaOH, single nanoparticles display subdiffusive motion along the axis normal to an aqueous liquid-organic liquid interface. This is because of an extended interfacial potential with a shallow well (∼1 kBT) that stretches a few µm into the organic phase, in contrast to previous molecular dynamics studies that reported narrow interfaces on the order of ∼1 nm. Spontaneous interfacial emulsification induced by NaOH results in the propagation of water-in-oil nanoemulsions into the organic solvent that creates an equilibrium hybrid-solvent composition that solvates the PTC. A greater mobility and longer residence time of the PTC at the potential well enhance the interfacial phase transfer process and catalytic efficiency.

Exploiting the upconversion luminescence, Lewis acid catalytic and photothermal properties of lanthanide-based nanomaterials for chemical and polymerization reactions.

Lanthanide-based nanocrystals possess three unique physical properties that make them attractive for facilitating photoreactions, namely photon upconversion luminescence, Lewis acid catalytic activity and photothermal properties. When co-doped with a suitable sensitizer and activator lanthanide ions, rare-earth fluoride nanocrystals upconvert near-infrared light to higher energy photons that can be used to excite photosensitizers that absorb ultraviolet and visible light in photocatalytic and photopolymerization reactions. Surface lanthanide ions on nanocrystals also have the propensity to behave as Lewis acid (LA) catalytic sites. In addition, NIR-light excited lanthanides such as Nd3+ undergo cross-relaxation interaction with neighbouring ground-state ions followed by non-radiative decay to generate heat (i.e., photothermal) which enhances the rate of chemical reactions. In this perspective, we provide a survey of the recent progress in the use of lanthanide-based nanocrystals as upconverting nanolamps, LA catalysts and photothermal nanoheaters in driving synthetic and polymerization reactions, and the challenges that need to be further addressed in order for this vibrant research area to develop and grow.

Unveiling Extreme Photoreduction Potentials of Donor-Acceptor Cyanoarenes to Access Aryl Radicals from Aryl Chlorides.

Since the seminal work of Zhang in 2016, donor-acceptor cyanoarene-based fluorophores, such as 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), have been widely applied in photoredox catalysis and used as excellent metal-free alternatives to noble metal Ir- and Ru-based photocatalysts. However, all the reported photoredox reactions involving this chromophore family are based on harnessing the energy from a single visible light photon, with a limited range of redox potentials from -1.92 to +1.79 V vs SCE. Here, we document the unprecedented discovery that this family of fluorophores can undergo consecutive photoinduced electron transfer (ConPET) to achieve very high reduction potentials. One of the newly synthesized catalysts, 2,4,5-tri(9H-carbazol-9-yl)-6-(ethyl(phenyl)amino)isophthalonitrile (3CzEPAIPN), possesses a long-lived (12.95 ns) excited radical anion form, 3CzEPAIPN•-*, which can be used to activate reductively recalcitrant aryl chlorides (Ered ≈ -1.9 to -2.9 V vs SCE) under mild conditions. The resultant aryl radicals can be engaged in synthetically valuable aromatic C-B, C-P, and C-C bond formation to furnish arylboronates, arylphosphonium salts, arylphosphonates, and spirocyclic cyclohexadienes.

Electron Transfer Quenching of Rhodamine 6G by N-Methylpyrrole Is an Unproductive Process in the Photocatalytic Heterobiaryl Cross-Coupling Reaction.

In the heterobiaryl cross-coupling reaction between aryl halides (Ar-X) and N-methylpyrrole (N-MP) catalyzed by rhodamine 6G (Rh6G+) under irradiation with visible light, a highly active and long-lived (millisecond time range) rhodamine 6G radical (Rh6G•) is formed upon electron transfer from N,N-diisopropylethylamine (DIPEA) to Rh6G+. In this study, we utilized steady-state and time-resolved spectroscopy techniques to demonstrate the existence of another electron-transfer process occurring from the relatively electron-rich N-MP to photoexcited Rh6G+ that was neglected in the previous reports. In this case, the radical Rh6G• formed is short-lived and undergoes rapid recombination (nanosecond time-range), rendering it ineffective in reducing Ar-X to aryl radicals Ar• that can subsequently be trapped by N-MP. This is further demonstrated via two model reactions involving 4'-bromoacetophenone and 1,3,5-tribromobenzene with insignificant product yields after visible-light irradiation in the absence of DIPEA. The unproductive quenching of photoexcited Rh6G+ by N-MP leads to a lower concentration of photocatalyst available for competitive charge transfer with DIPEA and hence decreases the efficiency of the cross-coupling reaction.

Increasing antibiotic activity by rapid bioorthogonal conjugation of drug to resistant bacteria using an upconverted light-activated photocatalyst.

Antibiotic vancomycin (Van) is often used as the drug of last resort to treat methicillin resistant Staphylococcus aureus. Due to the emergence of Van-resistant microbes, it is necessary to continuously design strategies to increase the efficacy of Van against resistant cells. In this study, an efficient method of bio-conjugating Van to bacteria is proposed using near-infrared (NIR)-light activation. A Nd3+-sensitized upconversion nanocrystal (UCNC) decorated with toluidine blue O (TB) on its surface undergoes upconverted energy transfer from the UCNC to TB when excited by 808 nm light. The photoexcited TB then catalyses the conversion of the dihydrotetrazine (dHTz) moiety in a Van-dHTz conjugate system to tetrazine which undergoes an efficient inverse electron demand Diels-Alder reaction with prior attached norbornene molecules on bacterial cell walls. The enhanced affinity of Van to bacteria by covalent bonding improves the activity of the drug against drug-resistant Enterococci, and the MIC is reduced by 6- to 7-fold as compared to neat Van. We demonstrate that the mode of action is due to increased inhibition of peptidoglycan cell wall biosynthesis. The findings in this study demonstrate that on-demand NIR-light activated bioorthogonal conjugation of Van to microbes is a viable alternative treatment in combating drug-resistant bacteria.

Polysulfide Anions as Visible Light Photoredox Catalysts for Aryl Cross-Couplings.

Polysulfide anions are endowed with unique redox properties, attracting considerable attentions for their applications in alkali metals-sulfur batteries. However, the employment of these anionic species in redox catalysis for small molecule synthesis remains underdeveloped due to their moderate-poor electrochemical potential in the ground state, whereas some of them are characterized by photoabsorptions in visible spectral regions. Herein, we disclose the use of polysulfide anions as visible light photoredox catalysts for aryl cross-coupling reactions. The reaction design enables single-electron reduction of aryl halides upon the photoexcitation of tetrasulfide dianions (S42-). The resulting aryl radicals are engaged in (hetero)biaryl cross-coupling, borylation, and hydrogenation in a redox catalytic regime involving S4• -/S42- and S3• -/S32- redox couples.

Ultrathin Near-Infrared Light Activated Nano-Hotplate Catalyst.

A combined photothermal-catalytic system that contains a single active element, without using different entities for separate roles (catalytic vs photothermal), is designed here for efficient catalytic reactions. Herein, ultrathin (sub-6 nm) rectangular-like KNdF4 nanoplates consisting of 3-4 unit cell layers are prepared where the Nd3+ ions act as a Lewis acid catalyst. In addition, the nanoplates undergo light-to-heat conversion when irradiated with NIR light due to cross-relaxation and nonradiative relaxation processes from excited Nd3+ . The cyanosilylation of a series of ketones is performed using the nano-hotplate catalysts to give near quantitative yields of the cyanohydrin trimethylsilyl ethers. This is because of the high surface area-to-volume ratio of the thin nanoplates that provides a large number of surface Nd3+ catalytic sites for reaction. The reaction kinetics are enhanced by the photothermal effect, leading to the observed > 10-fold increase in product yields.

Tuning the NIR downconversion luminescence and photothermal conversion efficiencies of MNdxY1-xF4 (M = Na and Li) nanocrystals for use in anti-counterfeiting labels with opposite displays.

Rare earth (RE3+ = Y3+ and Nd3+) alkali (M+ = Na+ or Li+) tetrafluoride nanocrystals adopt various morphologies and crystal structures depending on the M+-RE3+ size compatibility and Nd3+ concentration. This in turn affects the downconversion NIR luminescence and photothermal properties of the nanocrystals. For NaOH precursor, hexagonal NaNdxY1-xF4 nanocrystals are formed from the initially created cubic NaNdxY1-xF4 nanocrystals, whereas for LiOH precursor, tetragonal LiNd0.03Y0.97F4 nanocrystals are obtained. Due to the large size mismatch between Li+ and Nd3+, unstable LiNdxY1-xF4 undergoes phase separation to form either orthorhombic or hexagonal NdxY1-xF3 nanocrystals upon increasing the Nd3+ concentration. The latter dominates when Nd3+ is the majority rare earth element in the host matrix. NaNdxY1-xF4 nanocrystals display better luminescence and photothermal properties as compared to their Li+-based counterparts and the inverse relationship between emission and light-to-heat conversion efficiencies is exploited for anti-counterfeiting purposes. In this case, patterns deposited on different substrates (e.g., glass and Teflon) using Nd3+-concentrated nanocrystals, with efficient light-to-heat conversion and poor NIR luminescence properties, exhibit bright thermal and dim emission images when irradiated with 808 nm light. On the other hand, areas printed with Nd3+-diluted nanocrystals display dim thermal and bright emission images. Such anti-counterfeiting labels with opposite thermal and NIR emission displays provide enhanced security.

Enabling Mitochondrial Uptake of Lipophilic Dications Using Methylated Triphenylphosphonium Moieties.

Triphenylphosphonium (TPP+) species comprising multiple charges, i.e., bis-TPP+, are predicted to be superior mitochondrial-targeting vectors and are expected to have mitochondrial accumulations 1000-fold greater than TPP+, the current "gold standard". However, bis-TPP+ vectors linked by short hydrocarbon chains ( n < 5) are unable to be taken up by the mitochondria, thus hindering their development as mitochondrial delivery vectors. Through the incorporation of methylated TPP+ moieties (T*PP+), we successfully enabled the accumulation of bis-TPP+ with a short linker chain in isolated mitochondria, as measured by high performance liquid chromatography. These experimental results are further supported by molecular dynamics and ab initio calculations, revealing the strong correlations between mitochondria uptake and molecular volume, surface area, and chemical hardness. Most notably, the molecular volume has been shown to be a strong predictor of accumulation for both mono- and bis-TPP+ salts. Our study underscores the potential of T*PP+ moieties as alternative mitochondrial vectors to overcome low permeation into the mitochondria.

NIR nanoprobe-facilitated cross-referencing manifestation of local disease biology for dynamic therapeutic response assessment.

Pharmacological interventions for effective treatment require opportune, dynamic and accurate manifestation of pathological status. Traditional clinical techniques relying on biopsy-based histological examinations and blood tests are dramatically restricted due to their invasiveness, unsatisfactory precision, non-real-time reporting and risk of complications. Although current strategies through molecular imaging enable non-invasive and spatiotemporal mapping of pathological changes in intact organisms, environment-activatable, sensitive and quantitative sensing platforms, especially for dynamic feedback of the therapeutic response, are still urgently desired in practice. Herein, we innovatively integrate deep-tissue penetrable multispectral optoacoustic tomography (MSOT) and near-infrared (NIR) optical imaging based technology by tailoring a free radical-responsive chromophore with photon-upconverting nanocrystals. During the therapeutic process, the specific reactions between the drug-stimulated reactive oxygen species (ROS) and radical-sensitive probes result in an absorption shift, which can be captured by MSOT. Meanwhile, the radical-triggered reaction also induces multispectral upconversion luminescence (UCL) responses that exhibit the opposite trend in comparison to MSOT. Such reversed-ratiometric dual-modal imaging outcomes provide an ideal cross-referencing system that guarantees the maximum sensing specificity and sensitivity, thus enabling precise disease biology evaluation and treatment assessments in vivo.

Degenerative xanthate transfer to olefins under visible-light photocatalysis.

The degenerative transfer of xanthates to olefins is enabled by the iridium-based photocatalyst [Ir{dF(CF3)ppy}2(dtbbpy)](PF6) under blue LED light irradiation. Detailed mechanistic investigations through kinetics and photophysical studies revealed that the process operates under a radical chain mechanism, which is initiated through triplet-sensitization of xanthates by the long-lived triplet state of the iridium-based photocatalyst.

Concentrating Immiscible Molecules at Solid@MOF Interfacial Nanocavities to Drive an Inert Gas-Liquid Reaction at Ambient Conditions.

Gas-liquid reactions form the basis of our everyday lives, yet they still suffer poor reaction efficiency and are difficult to monitor in situ, especially at ambient conditions. Now, an inert gas-liquid reaction between aniline and CO2 is driven at 1 atm and 298 K by selectively concentrating these immiscible reactants at the interface between metal-organic framework and solid nanoparticles (solid@MOF). Real-time reaction SERS monitoring and simulations affirm the formation of phenylcarbamic acid, which was previously undetectable because they are unstable for post-reaction treatments. The solid@MOF ensemble gives rise to a more than 28-fold improvement to reaction efficiency as compared to ZIF-only and solid-only platforms, emphasizing that the interfacial nanocavities in solid@MOF are the key to enhance the gas-liquid reaction. Our strategy can be integrated with other functional materials, thus opening up new opportunities for ambient-operated gas-liquid applications.

Lipopolysaccharide-affinity copolymer senses the rapid motility of swarmer bacteria to trigger antimicrobial drug release.

An intelligent drug release system that is triggered into action upon sensing the motion of swarmer P. mirabilis is introduced. The rational design of the drug release system focuses on a pNIPAAm-co-pAEMA copolymer that prevents drug leakage in a tobramycin-loaded mesoporous silica particle by covering its surface via electrostatic attraction. The copolymer chains are also conjugated to peptide ligands YVLWKRKRKFCFI-NH2 that display affinity to Gram-negative bacteria. When swarmer P. mirabilis cells approach and come in contact with the particle, the copolymer-YVLWKRKRKFCFI-NH2 binds to the lipopolysaccharides on the outer membrane of motile P. mirabilis and are stripped off the particle surface when the cells move away; hence releasing tobramycin into the swarmer colony and inhibiting its expansion. The release mechanism is termed Motion-Induced Mechanical Stripping (MIMS). For swarmer B. subtilis, the removal of copolymers from particle surfaces via MIMS is not apparent due to poor adherence between bacteria and copolymer-YVLWKRKRKFCFI-NH2 system.

Vancomycin Determination by Disrupting Electron-Transfer in a Fluorescence Turn-On Squaraine-Anthraquinone Triad.

A highly sensitive and selective probe for Vancomycin (Van) in aqueous and serum samples is developed in this study. The probe is based on a triad consisting of a near-infrared squaraine dye (Seta-640) conjugated to two anthraquinone molecules via Lys-d-Ala-d-Ala peptides. In the absence of Van, the close proximity and efficient electron-transfer from the excited Seta-640 dye to anthraquinone result in significant fluorescence quenching of the dye ("off"-state). When Van is added, the antibiotic molecules bind with high affinity to the -d-Ala-d-Ala ligands in a 2:1 stoichiometry (Van:triad), resulting in fluorescence recovery that is as high as 30 times ("on"-state). Even though bound Van enhances the fluorescence by reducing the rate of (intrinsic) polarity-induced nonradiative decay process, this effect plays only a minor role. Instead, the main reason behind the observed fluorescence recovery after drug binding is the effective inhibition of electron-transfer; plausibly arising from a steric-induced lengthening of the spatial separation between electron donor and acceptor. The probe has detection limits of 7.0 and 96.9 nM in buffer and human serum, respectively, operates in the clinically relevant range, is insensitive to Van crystalline degradation product (CDP-1), and is easy to operate by using a commonly available fluorescence spectrometer.

Transcending the slow bimolecular recombination in lead-halide perovskites for electroluminescence.

The slow bimolecular recombination that drives three-dimensional lead-halide perovskites' outstanding photovoltaic performance is conversely a fundamental limitation for electroluminescence. Under electroluminescence working conditions with typical charge densities lower than 1015 cm-3, defect-states trapping in three-dimensional perovskites competes effectively with the bimolecular radiative recombination. Herein, we overcome this limitation using van-der-Waals-coupled Ruddlesden-Popper perovskite multi-quantum-wells. Injected charge carriers are rapidly localized from adjacent thin few layer (n≤4) multi-quantum-wells to the thick (n≥5) multi-quantum-wells with extremely high efficiency (over 85%) through quantum coupling. Light emission originates from excitonic recombination in the thick multi-quantum-wells at much higher decay rate and efficiency than bimolecular recombination in three-dimensional perovskites. These multi-quantum-wells retain the simple solution processability and high charge carrier mobility of two-dimensional lead-halide perovskites. Importantly, these Ruddlesden-Popper perovskites offer new functionalities unavailable in single phase constituents, permitting the transcendence of the slow bimolecular recombination bottleneck in lead-halide perovskites for efficient electroluminescence.

Unique Triphenylphosphonium Derivatives for Enhanced Mitochondrial Uptake and Photodynamic Therapy.

In this study, unique methyl-functionalized derivatives (T*PP+) of the drug carrier triphenylphosphonium (TPP+) that exhibit significant enhancement of the accumulation of both the cation and its conjugated cargo in cell mitochondria are designed. We show that the presence of methyl group(s) at key positions within the phenyl ring results in an increase in the hydrophobicity and solvent accessible surface area of T*PP+. In particular, when the para position of the phenyl ring in T*PP+ is functionalized with a methyl group, the cation is most exposed to the surrounding environment, leading to a large decrease in water entropy and an increase in the level of van der Waals interaction with and partition into a nonpolar solvent. Therefore, stronger binding between the hydrophobic T*PP+ and mitochondrial membrane occurs. This is exemplified in a (hexachloro-fluorescein)-TPP+ conjugate system, where an ∼12 times increase in the rate of mitochondrial uptake and a 2 times increase in photodynamic therapy (PDT) efficacy against HeLa and FU97 cancer cells are achieved when TPP+ is replaced with T*PP+. Importantly, nearly all the FU97 cells treated with the (hexachloro-fluorescein)-T*PP+ conjugate are killed as compared to only half the population of cells in the case of the (hexachloro-fluorescein)-TPP+ conjugate at a similar PDT light dosage. This study thus forms a platform for the healthcare community to explore alternative TPP+ derivatives that can act as optimal drug transporters for enhanced mitochondrially targeted therapies.

In vivo covalent cross-linking of photon-converted rare-earth nanostructures for tumour localization and theranostics.

The development of precision nanomedicines to direct nanostructure-based reagents into tumour-targeted areas remains a critical challenge in clinics. Chemical reaction-mediated localization in response to tumour environmental perturbations offers promising opportunities for rational design of effective nano-theranostics. Here, we present a unique microenvironment-sensitive strategy for localization of peptide-premodified upconversion nanocrystals (UCNs) within tumour areas. Upon tumour-specific cathepsin protease reactions, the cleavage of peptides induces covalent cross-linking between the exposed cysteine and 2-cyanobenzothiazole on neighbouring particles, thus triggering the accumulation of UCNs into tumour site. Such enzyme-triggered cross-linking of UCNs leads to enhanced upconversion emission upon 808 nm laser irradiation, and in turn amplifies the singlet oxygen generation from the photosensitizers attached on UCNs. Importantly, this design enables remarkable tumour inhibition through either intratumoral UCNs injection or intravenous injection of nanoparticles modified with the targeting ligand. Our strategy may provide a multimodality solution for effective molecular sensing and site-specific tumour treatment.

Nontoxic colloidal particles impede antibiotic resistance of swarming bacteria by disrupting collective motion and speed.

A monolayer of swarming B. subtilis on semisolid agar is shown to display enhanced resistance against antibacterial drugs due to their collective behavior and motility. The dynamics of swarming motion, visualized in real time using time-lapse microscopy, prevents the bacteria from prolonged exposure to lethal drug concentrations. The elevated drug resistance is significantly reduced when the collective motion of bacteria is judiciously disrupted using nontoxic polystyrene colloidal particles immobilized on the agar surface. The colloidal particles block and hinder the motion of the cells, and force large swarming rafts to break up into smaller packs in order to maneuver across narrow spaces between densely packed particles. In this manner, cohesive rafts rapidly lose their collectivity, speed, and group dynamics, and the cells become vulnerable to the drugs. The antibiotic resistance capability of swarming B. subtilis is experimentally observed to be negatively correlated with the number density of colloidal particles on the engineered surface. This relationship is further tested using an improved self-propelled particle model that takes into account interparticle alignment and hard-core repulsion. This work has pertinent implications on the design of optimal methods to treat drug resistant bacteria commonly found in swarming colonies.

Interplay of hole transfer and host-guest interaction in a molecular dyad and triad: ensemble and single-molecule spectroscopy and sensing applications.

A new molecular dyad consisting of a Cy5 chromophore and ferrocene (Fc) and a triad consisting of Cy5, Fc, and ß-cyclodextrin (CD) are synthesized and their photophysical properties investigated at both the ensemble and single-molecule levels. Hole transfer efficiency from Cy5 to Fc in the dyad is reduced upon addition of CD. This is due to an increase in the Cy5-Fc separation (r) when the Fc is encapsulated in the macrocyclic host. On the other hand, the triad adopts either a Fc-CD inclusion complex conformation in which hole transfer quenching of the Cy5 by Fc is minimal or a quasi-static conformation with short r and rapid charge transfer. Single-molecule fluorescence measurements reveal that r is lengthened when the triad molecules are deposited on a glass substrate. By combining intramolecular charge transfer and competitive supramolecular interaction, the triad acts as an efficient chemical sensor to detect different bioactive analytes such as amantadine hydrochloride and sodium lithocholate in aqueous solution and synthetic urine.

Efficient color-tunable multiexcitonic dual wavelength emission from Type II semiconductor tetrapods.

We synthesized colloidal InP/ZnS seeded CdS tetrapods by harnessing the structural stability of the InP/ZnS seed nanocrystals at the high reaction temperatures needed to grow the CdS arms. Because of an unexpected Type II band alignment at the interface of the InP/ZnS core and CdS arms that enhanced the occurrence of radiative excitonic recombination in CdS, these tetrapods were found to be capable of exhibiting highly efficient multiexcitonic dual wavelength emission of equal intensity at spectrally distinct wavelengths of ∼485 and ∼675 nm. Additionally, the Type II InP/ZnS seeded CdS tetrapods displayed a wider range of pump-dependent emission color-tunability (from red to white to blue) within the context of a CIE 1931 chromaticity diagram and possessed higher photostability due to suppressed multiexcitonic Auger recombination when compared to conventional Type I CdSe seeded CdS tetrapods. By employing time-resolved spectroscopy measurements, we were able to attribute the wide emission color-tunability to the large valence band offset between InP and CdS. This work highlights the importance of band alignment in the synthetic design of semiconductor nanoheterostructures, which can exhibit color-tunable multiwavelength emission with high efficiency and photostability.