Reversibly Tuning the Viscosity of Peptide-Based Solutions Using Visible Light.

Light can be used to design stimuli-responsive systems. We induce transient changes in the assembly of a low molecular weight gelator solution using a merocyanine photoacid. Through our approach, reversible viscosity changes can be achieved via irradiation, delivering systems where flow can be controlled non-invasively on demand.

Modulating the Lifetime of DNA Motifs Using Visible Light and Small Molecules.

Here we regulate the formation of dissipative assemblies built from DNA using a merocyanine photoacid that responds to visible light. The operation of our system and the relative distribution of species within it are controlled by irradiation time, initial pH value, and the concentration of a small-molecule binder that inhibits the reaction cycle. This approach is modular, does not require DNA modification, and can be used for several DNA sequences and lengths. Our system design allows for waste-free control of dissipative DNA nanotechnology, toward the generation of nonequilibrium, life-like nanodevices.

Water-Soluble Arylazoisoxazole Photoswitches.

Azoheteroarenes are emerging as powerful alternatives to azobenzene molecular photoswitches. In this study, water-soluble arylazoisoxazole photoswitches are introduced. UV/vis and NMR spectroscopy revealed moderate to very good photostationary states and reversible photoisomerization between the E- and Z-isomers over multiple cycles with minimal photobleaching. Several arylazoisoxazoles form host-guest complexes with ß- and γ-cyclodextrin with significant differences in binding constants for each photoisomer as shown by isothermal titration calorimetry and NMR experiments, indicating their potential for photoresponsive host-guest chemistry in water. One carboxylic acid functionalized arylazoisoxazole can act as a hydrogelator, allowing gel properties to be manipulated reversibly with light. The hydrogel was characterized by rheological experiments, atom force microscopy and transmission electron microscopy. These results demonstrate that arylazoisoxazoles can find applications as molecular photoswitches in aqueous media.

Gold and Silver Chains from Tetrahydrothiophenocucurbit[6]uril as Au or Ag-Nanoparticles.

Tetrahydrothiophenocucurbit[5 and 6]uril has been synthesized from tetrathiophenoglycoluril diether, providing thioether functionality at the exterior equatorial position of the cucurbituril cage. This functionality has been investigated for chemical modification through sulfoxide formation and subsequent Pummerer rearrangement to the acetoxy derivative of the tetrahydrothiophenocucurbit[5]uril. Nanoparticles of Au and Ag were prepared in the presence of tetrahydrothiophenocucurbit[6]uril, which curiously led to the formation of nanoparticle chains, growing in length over days to weeks.

Polydopamine as a Visible-Light Photosensitiser for Photoinitiated Polymerisation.

Polydopamine (PDA) is a synthetic model for melanin and has a wide range of opto-electronic properties that underpin its utility in applied and biological settings, from broadband light absorbance to possessing stable free radical species. Here, we show that PDA free radicals are photo-responsive under visible light irradiation, enabling PDA to serve as a photo-redox catalyst. Steady-state and transient electron spin resonance spectroscopy reveals a reversible amplification in semiquinone radical population within PDA under visible light. This photo-response modifies the redox potential of PDA and supports sensitisation of exogenous species via photoinduced electron transfer (PET). We demonstrate the utility of this discovery by employing PDA nanoparticles to photosensitise a common diaryliodonium photoinitiator and initiate free-radical polymerisation (FRP) of vinylic monomers. In situ 1 H nuclear magnetic resonance spectroscopy reveals an interplay between PDA-driven photosensitising and radical quenching during FRP under blue, green, and red light. This work provides crucial insights into the photoactive free radical properties of melanin-like materials and reveals a promising new application for polydopamine as a photosensitiser.

Response to Comment on "Following Molecular Mobility during Chemical Reactions: No Evidence for Active Propulsion" and "Molecular Diffusivity of Click Reaction Components: The Diffusion Enhancement Question".

In their Comment (DOI: 10.1021/jacs.2c02965) on two related publications by our groups (J. Am. Chem. Soc. 2021, 143, 20884-20890; DOI: 10.1021/jacs.1c09455) and another (J. Am. Chem. Soc. 2022, 144, 1380-1388; DOI: 10.1021/jacs.1c11754), Huang and Granick discuss the diffusion NMR measurements of molecules during a copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction. Here we respond to these comments and maintain that no diffusion enhancement was observed for any species during the reaction. We show that the relaxation agent does not interfere with the CuAAC reaction kinetics nor the diffusion of the molecules involved. Similarly, the gradient pulse length and diffusion time do not affect the diffusion coefficients. Peak overlap was completely removed in our study with the use of hydrazine as the reducing agent. The steady-state assumption does not hold for these diffusion measurements that take several minutes, which is the reason monotonic gradient orders are not suitable. Finally, we discuss the other reactions where similar changes in diffusion have been claimed. Our conclusions are fully supported by the results represented in our original JACS Article and the corresponding Supporting Information.

Polymer Grafting to Polydopamine Free Radicals for Universal Surface Functionalization.

Modifying surfaces using free radical polymerization (FRP) offers a means to incorporate the diverse physicochemical properties of vinyl polymers onto new materials. Here, we harness the universal surface attachment of polydopamine (PDA) to "prime" a range of different surfaces for free radical polymer attachment, including glass, cotton, paper, sponge, and stainless steel. We show that the intrinsic free radical species present in PDA can serve as an anchor point for subsequent attachment of propagating vinyl polymer macroradicals through radical-radical coupling. Leveraging a straightforward, twofold soak-wash protocol, FRP over the PDA-functionalized surfaces results in covalent polymer attachment on both porous and nonporous substrates, imparting new properties to the functionalized materials, including enhanced hydrophobicity, fluorescence, or temperature responsiveness. Our strategy is then extended to covalently incorporate PDA nanoparticles into organo-/hydrogels via radical cross-linking, yielding tunable PDA-polymer composite networks. The propensity of PDA free radicals to quench FRP is studied using in situ 1H nuclear magnetic resonance and electron paramagnetic resonance spectroscopy, revealing a surface area-dependent macroradical scavenging mechanism that underpins PDA-polymer conjugation. By combining the arbitrary surface attachment of PDA with the broad physicochemical properties of vinyl polymers, our strategy provides a straightforward route for imparting unlimited new functionality to practically any surface.

Visible-Light Switching of Metallosupramolecular Assemblies.

A photoswitchable ligand and palladium(II) ions form a dynamic mixture of self-assembled metallosupramolecular structures. The photoswitching ligand is an ortho-fluoroazobenzene with appended pyridyl groups. Combining the E-isomer with palladium(II) salts affords a double-walled triangle with composition [Pd3 L6 ]6+ and a distorted tetrahedron [Pd4 L8 ]8+ (1 : 2 ratio at 298 K). Irradiation with 410 nm light generates a photostationary state with approximately 80 % of the E-isomer of the ligand and results in the selective disassembly of the tetrahedron, the more thermodynamically stable structure, and the formation of the triangle, the more kinetically inert product. The triangle is then slowly transformed back into the tetrahedron over 2 days at 333 K. The Z-isomer of the ligand does not form any well-defined structures and has a thermal half-life of 25 days at 298 K. This approach shows how a thermodynamically preferred self-assembled structure can be reversibly pumped to a kinetic trap by small perturbations of the isomer distribution using non-destructive visible light.

Visible-Light-Responsive Self-Assembled Complexes: Improved Photoswitching Properties by Metal Ion Coordination.

A photoswitchable ligand based on azobenzene is self-assembled with palladium(II) ions to form a [Pd2 (E-L)4 ]4+ cage. Irradiation with 470 nm light results in the near-quantitative switching to a monomeric species [Pd(Z-L)2 ]2+ , which can be reversed by irradiation with 405 nm light, or heat. The photoswitching selectivity towards the metastable isomer is significantly improved upon self-assembly, and the thermal half-life is extended from 40 days to 850 days, a promising approach for tuning photoswitching properties.

Large, Tunable, and Reversible pH Changes by Merocyanine Photoacids.

Molecular photoswitches capable of generating precise pH changes will allow pH-dependent processes to be controlled remotely and noninvasively with light. We introduce a series of new merocyanine photoswitches, which deliver reversible bulk pH changes up to 3.2 pH units (pH 6.5 to pH 3.3) upon irradiation with 450 nm light, displaying tunable and predictable timescales for thermal recovery. We present models to show that the key parameters for optimizing the bulk pH changes are measurable: the solubility of the photoswitch, the acidity of the merocyanine form, the thermal equilibrium position between the spiropyran and the merocyanine isomers, and the increased acidity under visible light irradiation. Using ultrafast transient absorption spectroscopy, we determined the quantum yields for the ring-closing reaction and found that the lifetimes of the transient cis-merocyanine isomers ranged from 30 to 550 ns. Quantum yields did not appear to be a limitation for bulk pH switching. The models we present use experimentally determined parameters and are, in principle, able to predict the change in pH obtained for any related merocyanine photoacid.

Following Molecular Mobility during Chemical Reactions: No Evidence for Active Propulsion.

The reported changes in self-diffusion of small molecules during reactions have been attributed to "boosted mobility". We demonstrate the critical role of changing concentrations of paramagnetic ions on nuclear magnetic resonance (NMR) signal intensities, which led to erroneous measurements of diffusion coefficients. We present simple methods to overcome this problem. The use of shuffled gradient amplitudes allows accurate diffusion NMR measurements, even with time-dependent relaxation rates caused by changing concentrations of paramagnetic ions. The addition of a paramagnetic relaxation agent allows accurate determination of both diffusion coefficients and reaction kinetics during a single experiment. We analyze a copper-catalyzed azide-alkyne cycloaddition "click" reaction, for which boosted mobility has been claimed. With our methods, we accurately measure the diffusive behavior of the solvent, starting materials, and product and find no global increase in diffusion coefficients during the reaction. We overcome NMR signal overlap using an alternative reducing agent to improve the accuracy of the diffusion measurements. The alkyne reactant diffuses slower as the reaction proceeds due to binding to the copper catalyst during the catalytic cycle. The formation of this intermediate was confirmed by complementary NMR techniques and density functional theory calculations. Our work calls into question recent claims that molecules actively propel or swim during reactions and establishes that time-resolved diffusion NMR measurements can provide valuable insight into reaction mechanisms.

Singlet Fission in Concentrated TIPS-Pentacene Solutions: The Role of Excimers and Aggregates.

The excited-state dynamics of 6,13-bis(triisopropylsilylethynyl)pentacene is investigated to determine the role of excimer and aggregate formation in singlet fission in high-concentration solutions. Photoluminescence spectra were measured by excitation with the evanescent wave in total internal reflection, in order to avoid reabsorption effects. The spectra over nearly two magnitudes of concentration were nearly identical, with no evidence for excimer emission. Time-correlated single-photon counting measurements confirm that the fluorescence lifetime shortens with concentration. The observed rate constant grows at high concentrations, and this effect is modeled in terms of the hard-sphere radial distribution function. NMR measurements confirm that aggregation takes place with a binding constant of between 0.14 and 0.43 M-1. Transient absorption measurements are consistent with a diffusive encounter mechanism for singlet fission, with hints of more rapid singlet fission in aggregates at the highest concentration measured. These data show that excimers do not play the role of an emissive intermediate in exothermic singlet fission in solution and that, while aggregation occurs at higher concentrations, the mechanism of singlet fission remains dominated by diffusive encounters.

Visible Light Stimulated Bistable Photo-Switching in Defect Engineered Metal-Organic Frameworks.

The incorporation of photoactive donor-acceptor Stenhouse adduct (DASA) moieties into Metal-Organic Frameworks (MOFs) provides a new route to the development of visible light switching materials. Herein, a DUT-5 mixed-linker defect series was exploited to produce a derivative group of DASA-modified materials via postsynthetic modification (PSM). The photoactive MOFs exhibited conversion stimulated by visible wavelengths and were stable following multiple cycles. Thermodynamic and metastable states persisted over an extended time period.

Ultra-Low Molecular Weight Photoswitchable Hydrogelators.

Two photoswitchable arylazopyrozoles form hydrogels at a concentration of 1.2 % (w/v). With a molecular weight of 258.28 g mol-1 , these are the lowest known molecular weight hydrogelators that respond reversibly to light. Photoswitching of the E- to the Z-form by exposure to 365 nm light results in a macroscopic gel→sol transition; nearly an order of magnitude reduction in the measured elastic and loss moduli. In the case of the meta-arylazopyrozole, cryogenic transmission electron microscopy suggests that the 29±7 nm wide sheets in the E-gel state narrow to 13±2 nm upon photoswitching to the predominantly Z-solution state. Photoswitching for meta-arylazopyrozole is reversible through cycles of 365 nm and 520 nm excitation with little fatigue. The release of a rhodamine B dye encapsulated in gels formed by the arylazopyrozoles is accelerated more than 20-fold upon photoswitching with 365 nm light, demonstrating these materials are suitable for light-controlled cargo release.

Controlled Diffusion of Photoswitchable Receptors by Binding Anti-electrostatic Hydrogen-Bonded Phosphate Oligomers.

Dihydrogen phosphate anions are found to spontaneously associate into anti-electrostatic oligomers via hydrogen bonding interactions at millimolar concentrations in DMSO. Diffusion NMR measurements supported formation of these oligomers, which can be bound by photoswitchable anion receptors to form large bridged assemblies of approximately three times the volume of the unbound receptor. Photoisomerization of the oligomer-bound receptor causes a decrease in diffusion coefficient of up to 16%, corresponding to a 70% increase in effective volume. This new approach to external control of diffusion opens prospects in controlling molecular transport using light.

Visible-Light Photoswitching by Azobenzazoles.

Three visible-light responsive photoswitches are reported, azobis(1-methyl-benzimidazole) (1), azobis(benzoxazole) (2) and azobis(benzothiazole) (3). Photostationary distributions are obtained upon irradiation with visible light comprising approximately 80 % of the thermally unstable isomer, with thermal half-lives up to 8 min and are mostly invariant to solvent. On protonation, compound 1H+ has absorption extending beyond 600 nm, allowing switching with yellow light, and a thermal half-life just under 5 minutes. The two isomers have significantly different pKa values, offering potential as a pH switch. The absorption spectra of 2 and 3 are insensitive to acid, although changes in the thermal half-life of 3 indicate more basic intermediates that significantly influence the thermal barrier to isomerization. These findings are supported by high-level ab initio calculations, which validate that protonation occurs on the ring nitrogen and that the Z isomer is more basic in all cases.

Anion Binding Affinity: Acidity versus Conformational Effects.

High-level quantum chemical calculations were used to elucidate the gas- and solution-phase conformational equilibria for a series of symmetrically substituted (thio)ureas, (thio)squaramides, and croconamides. Gas-phase calculations predict that the thermodynamic conformer of many of these anion receptors is not the dual-hydrogen-bond-facilitating anti-anti conformer as is commonly assumed. For N,N'-diaryl thiosquaramides and croconamides, the syn-syn conformer is typically the predominant conformer. Solution-phase calculations show that the anti-anti conformer is increasingly stabilized as the polarity of the solvent increases. However, the syn-syn conformer remains the lowest energy conformation for croconamides. These predictions are used to explain the acidity versus chloride binding affinity correlations recently reported for some of these compounds. The chloride binding constants for thioureas and croconamides are significantly lower than expected on the basis of their pKa values, and this may be due in part to the need for these receptors to reorganize into the anti-anti conformer. Experimental NMR nuclear Overhauser effect (NOE) measurements of an asymmetrically substituted squaramide and its thio analogue are consistent with the syn-syn conformation being predominant at 298 K. The conformational equilibria should therefore be an important consideration for the design and development of future anion receptors and organocatalysts.

Photophysical Activity and Host-Guest Behavior of Ruthenium Polypyridyl Catalysts Encapsulated in Cucurbit[10]uril.

This work outlines a strategy to combine the use of visible light and confined spaces to form a supramolecular photocatalyst system. Polypyridyl ruthenium(II) complexes [Ru(bpy)3]2+ (bpy = 2,2'-bipyridine), [Ru(bpy)2(bpm)]2+ (bpm = 2,2'-bipyrimidine), and [Ru(bpy)2(bpz)]2+ (bpz = 2,2'-bipyrazine) are encapsulated in cucurbit[10]uril to form host-guest systems in aqueous solution. The photophysical properties of the complexes are altered by encapsulation, with improved emissive behavior for the heteroleptic complexes. Oxidative quenching of the photocatalyst's excited state via intermolecular charge transfer to methyl viologen can occur within the internal cavity, which acts to preorganize the reagents. The host-guest system containing [Ru(bpy)3]2+ can bind suitable substrates, and essential criteria for its use as a supramolecular photocatalyst are investigated.

Visible Light-Responsive Drug Delivery Nanoparticle via Donor-Acceptor Stenhouse Adducts (DASA).

Stimuli-responsive drug release from a nanocarrier triggered by light enables the control of the amount of drug locally. Here, block copolymer micelles based on poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) as the hydrophilic block and a polymer with pendant donor-acceptor Stenhouse adducts (DASA) are used as a means to trigger the release of drugs under green light. The micelles are loaded with ellipticine to yield light-responsive nanoparticles with sizes of around 35 nm according to transmission electron microscopy (TEM) analysis. Two micelles with a drug loading content of 4.75 and 7.4 wt% are prepared, but the micelle with the higher drug loading content leads to substantial protein adsorption. The release of ellipticine from the micelle, which is monitored using the polarity-sensitive fluorescence of ellipticine, can be switched on by light and off by thermal recovery of DASA in the dark. The micelles are readily taken up by Michigan Cancer Foundation-7 breast cancer cells. Subsequent light irradiation leads to enhanced drug release inside the cell as seen by the enhanced fluorescence.

A Photophysical Study of Sensitization-Initiated Electron Transfer: Insights into the Mechanism of Photoredox Activity.

The development of photocatalytic reactions has provided many novel opportunities to expand the scope of synthetic organic chemistry. In parallel with progress towards uncovering new reactivity, there is consensus that efforts focused on providing detailed mechanistic insight in order to uncover underlying excited-state reactions are essential to maximise formation of desired products. With this in mind, we have investigated the recently reported sensitization-initiated electron transfer (SenI-ET) reaction for the C-H arylation of activated aryl halides. Using a variety of techniques, and in particular nanosecond transient absorption spectroscopy, we are able to distinguish several characteristic signals from the excited-state species involved in the reaction, and subsequent kinetic analysis under various conditions has facilitated a detailed insight into the likely reaction mechanism.