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Curcumin is a medicinal agent that exhibits anti-cancer and anti-Alzheimer's disease properties. It has a keto-enol moiety that gives rise to many of its chemical properties including metal complexation and acid-base equilibria. A previous study has shown that keto-enol tautomerization at this moiety is implicated in the anti-Alzheimer's disease effect of curcumin, highlighting the importance of this process. In this study, tautomerization of curcumin in methanol, acetone and acetonitrile was investigated using time-resolved 1 H nuclear magnetic resonance spectroscopy. Curcumin undergoes hydrogen-deuterium exchange with the solvents and the proton resonance peak corresponding to the hydrogen at the α-carbon position (C α ) decays as a function of time, signifying deuteration at this position. Because tautomerization is the rate limiting step in the deuteration of curcumin at the C α position, the rate of tautomerization is inferred from the rate of deuteration. The rate constant of tautomerization of curcumin shows a temperature dependence and analysis using the Arrhenius equation revealed activation energies ( E a ) of tautomerization of (80.1 ± 5.9), (64.1 ± 1.0) and (68.3 ± 5.5) kJ mol -1 in methanol, D 2 O/acetone and D 2 O/acetonitrile, respectively. Insight into the role of water in tautomerization of curcumin was further offered by density functional theory studies. The transition state of tautomerization was optimized in the presence of water molecules. The results show a hydrogen-bonded solvent bridge between the diketo moiety and C α of curcumin. The E a of tautomerization of curcumin shows a strong dependence on the number of water molecules in the solvent bridge, indicating the critical role played by the solvent bridge in catalyzing tautomerization of curcumin.

Development of both organic photovoltaics (OPVs) and organic photocatalysts has focused on utilizing the bulk heterojunction (BHJ). The BHJ promotes charge separation and enhances the carrier lifetime, but may give rise to increased charge traps, hindering performance. Here, high photocatalytic and photovoltaic performance is displayed by electron donor-acceptor (D-A) nanoparticles (NPs) and films, using the nonfullerene acceptor Y6 and polymer donor PIDT-T8BT. In contrast to conventional D-A systems, the charge generation in PIDT-T8BT:Y6 NPs is mainly driven by Y6, allowing a high performance even at a low D:A mass ratio of 1:50. The high performance at the low mass ratio is attributed to the amorphous behavior of PIDT-T8BT. Low ratios are generally thought to yield lower efficiency than the more conventional ≈1:1 ratio. However, the OPVs exhibit peak performance at a D:A ratio of 1:5. Similarly the NPs used for photocatalytic hydrogen evolution show peak performance at the 1:6.7 D:A ratio. Interestingly, for the PIDT-T8BT:Y6 system, as the polymer proportion increases, a reduced photocatalytic and photovoltaic performance is observed. The unconventional D:A ratios provide lower recombination losses and increased charge-carrier lifetime with undisrupted ambipolar charge transport in bulk Y6, enabling better performance than conventional ratios. This work reports novel light-harvesting materials in which performance is reduced due to unfavorable morphology as D:A ratios move toward conventional ratios of 1:1.2-1:1., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Polyacenes, such as tetracene and pentacene, are common model systems for the study of photophysical phenomena such as singlet fission (SF) and triplet fusion, processes which may lead to increased photovoltaic efficiencies. While they exhibit desirable photophysical properties, these materials are not photostable and convert to unwanted endoperoxides in the presence of oxygen and light, limiting their use in real-world applications. Not only does oxygen degrade polyacenes but also it can affect their photophysics, leading to both the sensitization and quenching of different excited states. In this study, we characterize the effect of oxygen on 5,12-bis(triisopropylsilylethynyl) tetracene (TIPS-Tn) and 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-Pn) using transient absorption spectroscopy, and show that oxygen can significantly influence the population of excited states, in particular enhancing the polyacene triplet population. We additionally combine the time-resolved excited-state dynamics with photodegradation studies to determine the predominant mechanism of photooxidation, which has previously been unclear. We find that both molecules photodegrade predominantly via singlet oxygen; however, for TIPS-Tn, this occurs through the triplet state, whereas for TIPS-Pn, degradation occurs through the excited singlet. The photodegradation of TIPS-Tn is thus enhanced by faster rates of SF, whereas SF in TIPS-Pn increases the molecule's photostability. This work has implications both for the design of new materials for next-generation photovoltaics that can avoid photooxidation and for the study of their photophysics in real-world environments.

Singlet fission (SF) holds the promise to circumvent the photovoltaic efficiency limit to reach a power-conversion efficiency above 34%. SF of TIPS-pentacene (TIPS-Pn) has been investigated but its mechanism is yet to be well elucidated. Recently, we developed a nanoparticle (NP) system, in which doping of TIPS-Pn in a host matrix yields a range of average intermolecular distances, d , to study the dependence of SF in TIPS-Pn on d . At large d values, where the bimolecular SF process should be unfavourable, a relatively high SF quantum yield ( Φ SF ) is still observed, which implies a deviation from a random distribution of TIPS-Pn throughout the NP. Here, using polarisation-sensitive femtosecond time-resolved spectroscopy and Monte Carlo simulations of exciton migration and SF, we quantify the level of clustering of TIPS-Pn in the host matrix, which is responsible for the higher than expected Φ SF . The experimental data indicate a preservation of polarisation correlation by SF, which is uncommon because energy transfer in amorphous materials tends to result in depolarisation. We show that the preservation of polarisation correlation is due to SF upon exciton migration. Although exciton migration decorrelates polarisation, SF acts to remove decorrelated excitons to give an overall preservation of polarisation correlation.

Photosynthesis has been shown to be a highly efficient process for energy transfer in plants and bacteria. Like natural photosynthetic systems, the artificial light harvesting complex (LHC) BODIPY pillar[5]arene exhibits Förster resonance energy transfer (FRET). However, extensive characterisation of the BODIPY pillar[5]arene LHC to determine its suitability as an artificial LHC has yet to occur. In this paper we experimentally and computationally investigate the photophysical properties of the LHC by comparing the light absorption of the BODIPY LHC to individual BODIPY chromophores. Our results show evidence for quantum coherence, with oscillation frequencies of 100 cm -1 and 600 cm -1 , which are attributable to vibronic, or exciton-phonon type coupling. Computational analysis suggests strong couplings of the molecular orbitals of the LHC resulting from the stacking of neighbouring BODIPY chromophore units. Interestingly, we find a 40% reduction in the absorbance of light for the BODIPY LHC compared to the individual chromophores which we attribute to electronic interactions between the conjugated π-systems of the BODIPY chromophores and the pillar[5]arene backbone.

Singlet fission (SF), a process that produces two triplet excitons from one singlet exciton, has attracted recent interest for its potential to circumvent the detailed-balance efficiency limit of single-junction solar cells. For the potential of SF to be fully realized, accurate assignment and quantification of SF is necessary. Intersystem crossing (ISC) is another process of singlet to triplet conversion that is important to distinguish from SF to avoid either over- or under-estimation of SF triplet production. Here, we quantify an upper bound on the rate of ISC in two commonly studied SF chromophores, TIPS-pentacene and TIPS-tetracene, by using transient absorption spectroscopy of solutions of varying concentrations in toluene. We show that SF in solutions of these acenes has previously been misidentified as ISC, and vice versa. By determining a bimolecular SF rate constant in concentrated solutions in which SF dominates over ISC, we distinguish triplet formation due to SF from triplet formation due to ISC and show that the characteristic time scale of ISC must be longer than 325 ns in TIPS-pentacene, while it must be longer than 118 ns in TIPS-tetracene. We additionally note that no excimer formation is observed in the relatively dilute (up to 8 mM) solutions studied here, indicating that previous excimer formation observed at much higher concentrations may be partially due to aggregate formation. This work highlights that an accurate quantification of ISC is crucial as it leads to accurate determination of SF rate constants and yields.

Acetone and butanone were seen to emit blue light around 450 nm when excited in the green by a high intensity pulsed laser. The pathway of this anti-Stokes emission is believed to be multiphoton absorption followed by phosphorescence, with emission being observed in the samples at cryogenic temperatures below their melting point and not seen from either ketone in their cold liquid state. Given the widespread nature of these simple ketones in off-world bodies and their potential importance as an organic resource for Space Resource Utilization, signals which enable the identification and tracing of these materials are of use in applications from remote sensing and mapping to monitoring during extraction processes. While the excitation process has a low efficiency, the ability to use visible light for sensing of these targets has advantages over UV sources, such as the wider availability of high-powered lasers which could be utilized., (© 2022. The Author(s).)

TIPS-pentacene is a small-molecule organic semiconductor that is widely used in optoelectronic devices. It has been studied intensely owing to its ability to undergo singlet fission. In this study, we aim to develop further understanding of the coupling between the electronic and nuclear degrees of freedom of TIPS-pentacene (TIPS-Pn). We measured and analyzed the 2D electronic spectra of TIPS-Pn in solutions. Using center line slope (CLS) analysis, we characterized the frequency-fluctuation correlation function of the 0-0 vibronic transition. Strong oscillations in the CLS values were observed for up to 5 ps with a frequency of 264 cm -1 , which are attributable to a large vibronic coupling with the TIPS-Pn ring-breathing vibrational mode. In addition, detailed analysis of the CLS values allowed us to retrieve two spectral diffusion lifetimes, which are attributed to the inertial and diffusive dynamics of solvent molecules. Amplitude beating analysis also uncovered couplings with another vibrational mode at 1173 cm -1 . The experimental results can be described using the displaced harmonic oscillator model. By comparing the CLS values of the simulated data with the experimental CLS values, we estimated a Huang-Rhys factor of 0.1 for the ring-breathing vibrational mode. The results demonstrated how CLS analysis can be a useful method for characterizing the strength of vibronic coupling.

Introduction: Oncologists have traditionally administered the maximum tolerated doses of drugs in chemotherapy. However, these toxicity-guided doses may lead to suboptimal efficacy. CURATE.AI is an indication-agnostic, mechanism-independent and efficacy-driven personalised dosing platform that may offer a more optimal solution. While CURATE.AI has already been applied in a variety of clinical settings, there are no prior randomised controlled trials (RCTs) on CURATE.AI-guided chemotherapy dosing for solid tumours. Therefore, we aim to assess the technical and logistical feasibility of a future RCT for CURATE.AI-guided solid tumour chemotherapy dosing. We will also collect exploratory data on efficacy and toxicity, which will inform RCT power calculations. Methods and analysis: This is an open-label, single-arm, two-centre, prospective pilot clinical trial, recruiting adults with metastatic solid tumours and raised baseline tumour marker levels who are planned for palliative-intent, capecitabine-based chemotherapy. As CURATE.AI is a small data platform, it will guide drug dosing for each participant based only on their own tumour marker levels and drug doses as input data. The primary outcome is the proportion of participants in whom CURATE.AI is successfully applied to provide efficacy-driven personalised dosing, as judged based on predefined considerations. Secondary outcomes include the timeliness of dose recommendations, participant and physician adherence to CURATE.AI-recommended doses, and the proportion of clinically significant dose changes. We aim to initially enrol 10 participants from two hospitals in Singapore, perform an interim analysis, and consider either cohort expansion or an RCT. Recruitment began in August 2020. This pilot clinical trial will provide key data for a future RCT of CURATE.AI-guided personalised dosing for precision oncology. Ethics and dissemination: The National Healthcare Group (NHG) Domain Specific Review Board has granted ethical approval for this study (DSRB 2020/00334). We will distribute our findings at scientific conferences and publish them in peer-reviewed journals. Trial registration number: NCT04522284., Competing Interests: DH, ABl, and TK are inventors of pending and issued patents pertaining to artificial intelligence-based drug development and personalised medicine. DH and TK are shareholders of KYAN Therapeutics, which has licensed intellectual property pertaining to AI-based drug development. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tan, Teo, Tadeo, Peng, Soh, Du, Luo, Bandla, Sundar, Ho, Kee and Blasiak.)

In two-dimensional electronic spectroscopy (2DES), precise control of the arrival time of ultrashort laser pulses is critical to correlating the molecular states that are accessed in the experiment. In this work, we demonstrate a 2D electronic spectrometer design with an interferometric phase stability of ∼λ/250 at 600 nm. First, we present a new method for controlling pulse delay times based on transmission through pairs of optical flats rotated perpendicular to the beam propagation direction. Second, the calibration methods required to achieve adequate timing precision are also reported. Compared to existing designs using translating wedges, the rotating optical flats can achieve equivalent optical delay with a shorter path length in glass, reducing errors due to spectral dispersion of the broadband laser pulses used in 2DES. Our approach presents a simple, low-cost technique for multidimensional optical spectroscopy that is capable of resolving complex light-induced dynamics.

Nanoparticles of acenes exhibit highly efficient intermolecular singlet fission (SF). Recent reports indicate that altering the morphology of 6,13-bis-(triisopropylsilylethynyl)pentacene (TIPS-Pn) nanoparticles has a profound influence on their SF dynamics. Here, we show that poly(vinyl alcohol) (PVA) induces a phase transition in preformed TIPS-Pn nanoparticles. These nanoparticles are amorphous when initially formed but crystalline after addition of PVA. Surface characterization indicates that a diffuse PVA layer surrounds the nanoparticles. We propose that a periodic interaction between the hydroxyl groups of PVA and TIPS groups of TIPS-Pn on the nanoparticle surface induces a large-scale structural rearrangement to yield crystalline TIPS-Pn. Such reorganization in preformed organic nanoparticles is unprecedented, and we believe that this is the first report of such an effect induced by polymer adsorption. Transient absorption spectroscopic results reveal that SF within these nanoparticles is accelerated by an order of magnitude upon structural rearrangement.

Although the optoelectronic applications of metal halide perovskites have been intensively investigated in recent years, the fundamental carrier dynamics of zero-dimensional (0D) Cs4PbBr6 perovskites has been relatively underexplored; in particular, the nature of the green fluorescence is highly debated. Nevertheless, the unique photophysical properties are of immense interest for a variety of potential applications. In this work, the green emission of the CsPbBr3-Cs4PbBr6 perovskite composites is studied using temperature dependent photoluminescence (PL). The PL spectra at different temperatures simultaneously contain two sub-peaks (520 nm and 550 nm), which are ascribed to the emissions of the band-edge and the defect trapped exciton of CsPbBr3. This finding will help to understand the controversial photoluminescence currently observed in different 0D Cs4PbBr6 perovskites.

Singlet fission is a process whereby two triplet excitons can be produced from one photon, potentially increasing the efficiency of photovoltaic devices. Endothermic singlet fission is desired for a maximum energy-conversion efficiency, and such systems have been considered to form an excimer-like state with multiexcitonic character prior to the appearance of triplets. However, the role of the excimer as an intermediate has, until now, been unclear. Here we show, using 5,12-bis((triisopropylsilyl)ethynyl)tetracene in solution as a prototypical example, that, rather than acting as an intermediate, the excimer serves to trap excited states to the detriment of singlet-fission yield. We clearly demonstrate that singlet fission and its conjugate process, triplet-triplet annihilation, occur at a longer intermolecular distance than an excimer intermediate would impute. These results establish that an endothermic singlet-fission material must be designed to avoid excimer formation, thus allowing singlet fission to reach its full potential in enhancing photovoltaic energy conversion.

The excited states of conjugated polymers play a central role in their applications in organic solar photovoltaics. The delocalized excited states of conjugated polymers are short-lived (τ < 40 fs) but are imperative in the photovoltaic properties of these materials. Photoexcitation of poly(3-hexylthiophene) (P3HT) induces an excited-state absorption band, but the transitions that are involved are not well understood. In this work, calculations have been performed on P3HT analogues using nonlinear response time-dependent density functional theory to show that an increase in the oligomer length correlates with the dominance of the S 1 → S 3 transition. Furthermore, the predicted transition energy shows an excellent agreement with experiment. The calculations also yielded results on intramolecular charge transfer in P3HT due to the S 1 → S 3 transition, providing insight into the mechanism of exciton dissociation to form charge carriers.

The hot-phonon bottleneck effect in lead-halide perovskites (APbX 3 ) prolongs the cooling period of hot charge carriers, an effect that could be used in the next-generation photovoltaics devices. Using ultrafast optical characterization and first-principle calculations, four kinds of lead-halide perovskites (A=FA + /MA + /Cs + , X=I - /Br - ) are compared in this study to reveal the carrier-phonon dynamics within. Here we show a stronger phonon bottleneck effect in hybrid perovskites than in their inorganic counterparts. Compared with the caesium-based system, a 10 times slower carrier-phonon relaxation rate is observed in FAPbI 3 . The up-conversion of low-energy phonons is proposed to be responsible for the bottleneck effect. The presence of organic cations introduces overlapping phonon branches and facilitates the up-transition of low-energy modes. The blocking of phonon propagation associated with an ultralow thermal conductivity of the material also increases the overall up-conversion efficiency. This result also suggests a new and general method for achieving long-lived hot carriers in materials.

Curcumin is a yellow polyphenol with multiple medicinal effects. These effects, however, are limited due to its poor aqueous stability and solubility. A hydrogel of 3% octadecyl randomly substituted polyacrylate (PAAC18) has been shown to provide high aqueous stability for curcumin under physiological conditions, offering a route for photodynamic therapy. In this study, the excited-state photophysics of curcumin in the PAAC18 hydrogel is investigated using a combination of femtosecond transient absorption and fluorescence upconversion spectroscopy. The transient absorption results reveal a multiexponential decay in the excited-state kinetics with fast (1 ps & 15 ps) and slow (110 ps & ≈5 ns) components. The fast decay component exhibits a deuterium isotope effect with D 2 O in the hydrogel, indicating that the 15 ps decay component is attributable to excited-state intramolecular hydrogen atom transfer of curcumin in the PAAC18 hydrogel. In addition, solvent reorganisation of excited-state curcumin is investigated using multiwavelength femtosecond fluorescence upconversion spectroscopy. The results show that the dominant solvation response (τ = 0.08 ps) is a fast inertial motion owing to the presence of bulk-like water in the vicinity of the hydrophobic octadecyl substituents of the PAAC18 hydrogel. The results also show an additional response with longer time constants of 1 and 6 ps, which is attributable to translational diffusion of confined water molecules in the three-dimensional, cross-linking network of the octadecyl substituents of PAAC18. Overall, we show that excited-state intramolecular hydrogen atom transfer and solvent reorganisation are major photophysical events for curcumin in the PAAC18 hydrogel.

Curcumin-encapsulated polyester nanoparticles (Cur-polyester NPs) of approximately 100 nm diameter with a negatively charged surface were prepared using a one-step nanoprecipitation method. The Cur-polyester NPs were prepared using polylactic acid, poly(D,L-lactic-co-glycolic acid) and poly(ϵ-caprolactone) without any emulsifier or surfactant. The encapsulation of curcumin in these polyester NPs greatly suppresses curcumin degradation in the aqueous environment due to its segregation from water. In addition, the fluorescence of curcumin in polyester NPs has a quantum yield of 4 to 5%, which is higher than that of curcumin in micellar systems and comparable to those in organic solvents, further supporting the idea that the polyester NPs are capable of excluding water from curcumin. Furthermore, the results from femtosecond fluorescence upconversion spectroscopy reveal that there is a decrease in the signal amplitude corresponding to solvent reorganization of excited state curcumin in the polyester NPs compared with curcumin in micellar systems. The Cur-polyester NPs also show a lack of deuterium isotope effect in the fluorescence lifetime. These results indicate that the interaction between curcumin and water in the polyester NPs is significantly weaker than that in micelles. Therefore, the aqueous stability of curcumin is greatly improved due to highly effective segregation from water. The overall outcome suggests that the polyester NPs prepared using the method reported herein are an attractive system for encapsulating and stabilizing curcumin in the aqueous environment.

Curcumin is a biologically active polyphenol and a yellow pigment extracted from turmeric. Our previous study has shown effective encapsulation of curcumin using diamide linked γ-cyclodextrin dimers, namely 66γCD2su and 66γCD2ur, through cooperative 1:1 host-guest complexation. In this study, the excited-state dynamics of curcumin complexed with either 66γCD2su or 66γCD2ur in water are investigated using femtosecond transient absorption spectroscopy. Both 66γCD2su-curcumin and 66γCD2ur-curcumin complexes in water show only an excited-state absorption (ESA) band at 530 nm without any stimulated emission (SE) signals, indicating non-radiative decays as the major relaxation pathways. The ESA dynamics of 66γCD2su-curcumin are similar to those of 66γCD2ur-curcumin, consisting of a rapid growth component and three decay components. The growth component, which has a time constant of 0.25-0.41 ps, is assigned to solvent reorganization. The relatively fast decay components with time constants of 9.3-21.8 ps show significant deuterium isotope effect, consistent with the presence of excited-state intramolecular hydrogen atom transfer (ESIHT) of curcumin. The small-amplitude and slow decay components may be attributed to the dynamics of complexed curcumin and molecular motions due to flexibility of 66γCD2su and 66γCD2ur. In addition, transient absorption anisotropy measurements reveal slow rotational motions of 66γCD2su-curcumin and 66γCD2ur-curcumin complexes. The overall results show that complexation in 66γCD2su and 66γCD2ur has pronounced effects on the photophysics of curcumin.

Conjugated polymers are an important class of soft materials that exhibit a wide range of applications. The excited states of conjugated polymers, often referred to as excitons, can either deactivate to yield the ground state or dissociate in the presence of an electron acceptor to form charge carriers. These interesting properties give rise to their luminescence and the photovoltaic effect. Femtosecond spectroscopy is a crucial tool for studying conjugated polymers. Recently, more elaborate experimental configurations utilizing three optical pulses, namely, pump-push-probe and pump-dump-probe, have been employed to investigate the properties of excitons and charge-transfer states of conjugated polymers. These studies have revealed new insight into femtosecond torsional relaxation and detrapping of bound charge pairs of conjugated polymers. This Perspective highlights (1) the recent achievements by several research groups in using pump-push-probe and pump-dump-probe spectroscopy to study conjugated polymers and (2) future opportunities and potential challenges of these techniques.

The conversion of photoexcitations into charge carriers in organic solar cells is facilitated by the dissociation of excitons at the donor/acceptor interface. The ultrafast timescale of charge separation demands sophisticated theoretical models and raises questions about the role of coherence in the charge-transfer mechanism. Here, we apply two-dimensional electronic spectroscopy to study the electron transfer process in poly(3-hexylthiophene)/PCBM (P3HT/PCBM) blends. We report dynamics maps showing the pathways of charge transfer that clearly expose the significance of hot electron transfer. During this ultrafast electron transfer, vibrational coherence is directly transferred from the P3HT exciton to the P3HT hole polaron in the crystalline domain. This result reveals that the exciton converts to a hole with a similar spatial extent on a timescale far exceeding other photophysical dynamics including vibrational relaxation.

Hydrophobically modified polyacrylates are shown to suppress the degradation of the medicinal pigment curcumin under physiological conditions. In aqueous solution, the 3% octadecyl randomly substituted polyacrylate, PAAC18, forms micelle-like aggregates at a concentration of <1 wt % and a hydrogel at >1 wt %. Under both conditions, PAAC18 shows a remarkable ability to suppress the degradation of curcumin at pH 7.4 and 37 °C such that its degradation half-life is increased by 1600-2000-fold. The suppression of degradation is attributed to hydrophobic interactions between curcumin and the octadecyl substituents of PAAC18 within the micelle-like aggregates and the hydrogel, as indicated by 2D NOESY (1)H NMR spectroscopy. UV-visible absorption titration results are consistent with the interaction of curcumin with five octadecyl substituents on average, which appears to substantially exclude water and greatly decrease the curcumin degradation rate. Dynamic light scattering and zeta potential measurements show the average hydrodynamic diameters of the PAAC18 aggregates to be 0.86-1.15 μm with a negative surface charge. In contrast to the octadecyl substitution, the 3% dodecyl randomly substituted polyacrylate, PAAC12, shows a negligible effect on slowing the degradation of curcumin, consistent with the dodecyl substituents being insufficiently long to capture curcumin in a adequately hydrophobic environment. These observations indicate the potential for PAAC18 to act as a model drug delivery system.

The dynamics of high-energy excitons of poly(3-hexylthiophene) (P3HT) are shown to consist of torsional relaxation and exciton dissociation to form free carriers. In this work, we use pump-push-probe femtosecond transient absorption spectroscopy to study the highly excited states of P3HT in solution. P3HT excitons are generated using a pump pulse (400 nm) and allowed to relax to the lowest-lying excited state before re-excitation using a push pulse (900 or 1200 nm), producing high-energy excitons that decay back to the original excited state with both subpicosecond (0.16 ps) and picosecond (2.4 ps) time constants. These dynamics are consistent with P3HT torsional relaxation, with the 0.16 ps time constant assigned to ultrafast inertial torsional relaxation. Additionally, the signal exhibits an incomplete recovery, indicating dissociation of high-energy excitons to form charge carriers due to excitation by the push pulse. Our analysis indicates that charge carriers are formed with a yield of 11%.

Diamide linked γ-cyclodextrin (γ-CD) dimers are proposed as molecular-scale delivery agents for the anticancer agent curcumin. N,N'-Bis(6(A)-deoxy-γ-cyclodextrin-6(A)-yl)succinamide (66γCD2su) and N,N'-bis(6(A)-deoxy-γ-cyclodextrin-6(A)-yl)urea (66γCD2ur) markedly suppress the degradation of curcumin by forming a strong 1:1 cooperative binding complexes. The results presented in this study describe the potential efficacy of 66γCD2su and 66γCD2ur for intracellular curcumin delivery to cancer cells. Cellular viability assays demonstrated a dose-dependent antiproliferative effect of curcumin in human prostate cancer (PC-3) cells that was preserved by the curcumin-66γCD2su complex. In contrast, delivery of curcumin by 66γCD2ur significantly delayed the antiproliferative effect. We observed similar patterns of gene regulation in PC-3 cells for curcumin complexed with either 66γCD2su or 66γCD2ur in comparison to curcumin alone, although curcumin delivered by either 66γCD2su or 66γCD2ur induces a slightly higher up-regulation of heme oxygenase-1. Highlighting their nontoxic nature, neither 66γCD2su nor 66γCD2ur carriers alone had any measurable effect on cell proliferation or candidate gene expression in PC-3 cells. Finally, confocal fluorescence imaging and uptake studies were used to demonstrate the intracellular delivery of curcumin by 66γCD2su and 66γCD2ur. Overall, these results demonstrate effective intracellular delivery and action of curcumin when complexed with 66γCD2su and 66γCD2ur, providing further evidence of their potential applications to deliver curcumin effectively in cancer and other treatment settings.

Curcumin is a naturally occurring molecule with medicinal properties that is unstable in water, whose efficacy as a drug can potentially be enhanced by encapsulation inside a host molecule. In this work, the thermodynamics and mechanism of binding of curcumin to succinamide- and urea-linked γ-cyclodextrin (γ-CD) dimers in water are investigated by molecular dynamics simulations. The simulated binding constants of curcumin to succinamide- and urea-linked γ-CD dimers at 310 K are 11.3 × 10(6) M(-1) and 1.6 × 10(6) M(-1), respectively, matching well with previous experimental results of 8.7 × 10(6) M(-1) and 2.0 × 10(6) M(-1). The simulations reveal structural information about the encapsulation of curcumin inside the diamide-linked γ-CD dimers, with distinct qualitative differences observed for the two dimers. In particular, (1) the predominant orientation of curcumin inside the urea-linked γ-CD dimer is perpendicular to that in the succinamide-linked γ-CD dimer; (2) the magnitude of the angle between the planes of the cyclodextrins is larger for the succinamide-linked γ-CD dimer; and (3) curcumin exhibits greater configurational freedom inside the urea-linked γ-CD dimer. A consequence of some of these structural differences is that the dimer interior is more accessible to water in the succinamide-linked γ-CD dimer. These observations explain the higher stability and lower binding constant observed experimentally for curcumin in the urea-linked cyclodextrin γ-CD dimer compared with the succinamide-linked γ-CD dimer. More generally, the results demonstrate how stability and binding strength can be decoupled and thus separately optimized in host-guest systems used for drug delivery.

The dynamics of charge separation in aqueous suspensions of regioregular P3HT nanoparticles containing PCBM were investigated for the first time using femtosecond transient absorption spectroscopy. This investigation is supported by the recently reported use of regioregular P3HT/PCBM nanoparticles as charge trapping and storage devices. In this study, the presence of excited-state and charge-separated species, including singlet excitons, polymer polarons and free charges, generated in rr-P3HT/PCBM nanoparticles was identified through visible pump and visible/near-infrared probe femtosecond transient absorption spectroscopy at a range of electron acceptor concentrations. The decrease of the singlet exciton lifetime by charge transfer to PCBM is well described by a one-dimensional diffusion model with a P3HT domain size of approximately 5 nm for 5-50 wt % PCBM. This model also indicates that bimolecular recombination is the dominant charge recombination mechanism at 20 wt % PCBM and above.

Under certain conditions the conjugated polymer poly(3-hexylthiophene) (P3HT) self-assembles into high-aspect-ratio nanostructures (known as nanofibres, nanowires, or nanoribbons) when cooled below its solubility limit in a marginal solvent such as anisole. Such nanostructures are potentially beneficial for organic photovoltaic device performance. In this work, Langevin dynamics simulations of a coarse-grained model of P3HT in implicit anisole solvent are used to study the self-assembly of P3HT nanostructures for polymer chain lengths and concentrations used experimentally to prepare P3HT nanofibres. The coarse-grained model is parametrised to match the local structure and dynamics of an atomistic model with explicit solvent. Nanofibres are also prepared experimentally and characterised by atomic force microscopy and UV-vis spectroscopy. The simulations match the experimental phase behaviour of P3HT in anisole, showing aggregation of P3HT at 293 and 308 K but not at 323 or 353 K. Single-chain simulations at 293 K reveal two distinct nano-scale aggregate morphologies: hairpins and helices. Hairpin aggregates, which are the precursors of nanofibres, are slightly favoured energetically at 293 K for nuclei of the critical size of ≈80 monomers for aggregation. Consequently, chains in multi-chain aggregates adopt the hairpin morphology exclusively in simulations at experimental concentrations at 293 K. The simulated aggregate sizes match experimentally measured nanofibre widths. An estimate of the shift in UV-vis absorption of P3HT due to the change in conjugation length with aggregation in the simulations agrees reasonably well with experiment and shows that most of the spectral red shift that occurs with nanofibre formation is due to increased planarisation of the P3HT chains. In addition to providing insight into the mechanisms of nanofibre formation, the simulations resolve details of the molecular-level organisation of chains in P3HT nanofibres hitherto inaccessible by experiment.

Curcumin, a yellow pigment extracted from the rhizome of Curcuma longa, commonly known as turmeric, is the most active agent of this herbal medicine. The therapeutic activities of curcumin are exemplified not only by its enhancement in wound healing but also in the treatment of inflammation, cystic fibrosis, Alzheimer's disease and cancer. There are two critical issues involving low aqueous stability and solubility that limit the bioavailability and application of curcumin as a therapeutic agent. To address these issues, delivery systems of curcumin including surfactant micelles, liposomes, polymer nanoparticles, casein micelles, plasma proteins and cyclodextrins have been developed and characterized. From a biochemical perspective, the medicinal activities of curcumin are proposed to be related to an elevated level of transition metals including copper, zinc and iron in many disease sites, especially those in cancer and Alzheimer's disease. Previous studies have demonstrated the importance of copper(II)-curcumin complexes in DNA damage owing to the strong interaction between curcumin and copper(II). Curcumin, as an anti-oxidant, possesses the abilities to scavenge radicals and maintain the levels of anti-oxidant enzymes in the presence of copper. On the other hand, copper(II)-curcumin complexes show pro-oxidant effects by generating reactive oxygen species at a high free copper level in a reducing environment. This condition results in DNA damage and inhibition of vital signaling pathways in cancer cells, leading to apoptosis. In short, curcumin has dual roles as an anti-oxidant and a prooxidant in the presence of copper and these fascinating phenomena contribute greatly to its multiple medicinal effects.

Ligand-metal interaction between curcumin and Cu(II) in methanol and sodium dodecyl sulfate (SDS) micelles was investigated using fluorescence spectroscopy and transient absorption spectroscopy. The Cu(II) ion exhibits a high efficiency in quenching the fluorescence of curcumin. By quantifying fluorescence quenching as a function of Cu(II) concentration, the complexation constants, K(1) and K(2), for the formation of the 1 : 1 and 1 : 2 Cu(II)-curcumin complexes, [Cu(II)-Cur](+) and [Cu(II)-Cur(2)], have been determined. In methanol, K(1) and K(2) are (1.33 ± 0.47) × 10(8) M(-1) and (6.79 ± 1.77) × 10(5) M(-1), respectively, whereas those in SDS micelles are (9.90 ± 1.68) × 10(5) M(-1) and (1.70 ± 0.48) × 10(6) M(-1), respectively. The transient absorption spectra of curcumin and the Cu(II)-curcumin complexes from 520 nm to 700 nm show a combination of stimulated emission and excited state absorption (ESA). However, the transient absorption signal at 500 nm corresponds to ESA exclusively. For curcumin, the ESA kinetics exhibit two rising components with time constants of 0.9 ps and 8.2 ps in methanol, and 0.5 ps and 2.5 ps in SDS micelles, which are consistent with solvation dynamics of excited state curcumin in these media. In addition, the ESA kinetics show a decay component with a time constant of 125 ps in methanol and 64 ps in SDS micelles, reflecting the excited state intramolecular hydrogen atom transfer of curcumin in these media. The ESA kinetics of the Cu(II)-curcumin complexes exhibit a sharp rise and a fast decay with a time constant of approximately 1 ps in both media due to the strong interaction between Cu(II) and curcumin.

The photophysical properties of cyclocurcumin in various solvents are studied for the first time to shed light on the nonradiative processes of the parent compound, curcumin, which has a range of medicinal properties. Steady-state fluorescence and fluorescence-excitation spectra of cyclocurcumin in polar aprotic solvents are strongly dependent on excitation (λ(ex)) and emission (λ(em)) wavelength, respectively. The fluorescence quantum yield also depends on λ(ex) and increases with the viscosity of the medium. Time-resolved studies show nonexponential fluorescence decay in all solvents studied. The two fluorescence decay components of cyclocurcumin in alcohols exhibit a strong dependence on viscosity and temperature. NMR spectroscopy indicates that cyclocurcumin is entirely in the trans form with respect to the C6-C7 double bond in methanol, chloroform, and acetone. It is suggested that at least two conformational isomers about another single bond (C5-C6 or C7-C1″ or both) and that trans-to-cis isomerization about the C6-C7 double bond of these isomers provide the most likely means of rationalizing the steady-state spectra and the nonradiative decay mechanisms in both protic and aprotic polar solvents., (© 2011 American Chemical Society)

Diamide linked γ-cyclodextrin (γ-CD) dimers are used to capture curcumin and suppress its decomposition in water. In this study, succinamide and urea linked γ-CD dimers joined through the C6(A) carbon on each γ-CD are used. The γ-CD dimers, 66γCD(2)su and 66γCD(2)ur, show a remarkable ability to suppress the decomposition of curcumin and extend its half-life from less than 30 min to greater than 16 h. The 1:1 association of curcumin with 66γCD(2)su and 66γCD(2)ur has high stability constants of 8.7 × 10(6) M(-1) and 2.0 × 10(6) M(-1), respectively. In addition, 2D (1)H NOESY NMR results show specific hydrogen interactions in the association of curcumin with 66γCD(2)su and 66γCD(2)ur, consistent with the cooperative binding of curcumin by both γ-CD annuli of 66γCD(2)su and 66γCD(2)ur. The interactions between curcumin in the linked γ-CD dimers and surfactant micelles were studied using fluorescence spectroscopy. While linked γ-CD dimer-bound curcumin has a negligible fluorescence quantum yield, a significant increase in fluorescence intensity (Φ(fl) > 2%) in the presence of micelles suggests that curcumin is delivered to the micelle. The overall results indicate that the diamide linked γ-CD dimers are highly promising systems for curcumin delivery in vivo due to effective curcumin stabilization.

Density functional theory is used to obtain the lowest energy geometries of bis-aqua curcumin complexes and bis-curcumin complexes of Cu(I) and Cu(II). Three conformations of curcumin, obtained by rotation of the substituted aromatic groups, were considered in each case. Steric repulsion, due to the methoxy–methoxy interactions, was found to be an important factor in determining the lowest energy conformer of Cu(II)(curcumin)2 but was less important for the Cu(I) analog. Using a sufficiently large basis set, the results show that the lowest energy Cu(II)(curcumin)2 geometry is square planar around the copper atom, in contrast to the results from a previous study (Shen et al. THEOCHEM-J Mol Struct 2005, 757, 199). In addition, other studies suggested that the formation of this complex is followed by the reduction of Cu(II) to Cu(I). We also examined the singly occupied molecular orbital, spin density, and natural bond orbitals of Cu(II)(curcumin)2. While the former two analyses show little evidence of electron transfer from curcumin into the Cu center, the latter indicates that Cu(II) is partially reduced to Cu(I) as a consequence of complexation. Finally, we consider the bis-aqua curcumin and bis-curcumin complexes on a reaction path involving progressive displacement of water molecules by curcumin ligands. The results show that the bis-curcumin complex is the most stable Cu(II) complex, showing consistently exothermic steps in the reaction path. However, for Cu(I), the final step in the reaction path is essentially thermoneutral, indicating that the 1:1 and 1:2 Cu(I) complexes are equally stable thermodynamically.

We present strong evidence for the oxidation of conjugated polymers in the formation of conjugated polymer dots (CPdots) using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Although recent studies show that folding of the polymer chain into a compact 3D structure is involved in the formation of these nanoparticles, the process by which these intrinsically hydrophobic nanoscale particles circumvent aggregation in water is still not well understood. Zeta potential results show that these dots have a negatively charged surface at neutral pH, with a zeta potential and surface charge density of approximately -40 mV and (1.39 - 1.70) × 10(-2) C/m(2), respectively. In addition, quantitative elemental analysis of CPdots indicates that oxygen composes 7-13% of these nanoparticles. The overall results support the presence of chemical defects in forming a hydrophilic surface of CPdots. As a consequence, the charged surface contributes to inhibiting the aggregation of CPdots in water, leading to colloidal stability.

Colloidal solutions of surfactants that form micelles or vesicles are useful for solubilizing and stabilizing hydrophobic molecules that are otherwise sparingly soluble in aqueous solutions. In this paper we investigate the use of micelles and vesicles prepared from ionic surfactants for solubilizing and stabilizing curcumin, a medicinal natural product that undergoes alkaline hydrolysis in water. We identify spectroscopic signatures to evaluate curcumin partitioning and deprotonation in surfactant mixtures containing micelles or vesicles. These spectroscopic signatures allow us to monitor the interaction of curcumin with charged surfactants over a wide range of pH values. Titration data are presented to show the pH dependence of curcumin interactions with negatively and positively charged micelles and vesicles. In solutions of cationic micelles or positively charged vesicles, strong interaction between the Cur(-1) phenoxide ion and the positively charged surfactants results in a change in the acidity of the phenolic hydrogen and a lowering of the apparent lowest pK(a) value for curcumin. In the microenvironments formed by anionic micelles or negatively charged bilayers, our data indicates that curcumin partitions as the Cur(0) species, which is stabilized by interactions with the respective surfactant aggregates, and this leads to an increase in the apparent pK(a) values. Our results may explain some of the discrepancies within the literature with respect to reported pK(a) values and the acidity of the enolic versus phenolic protons. Hydrolysis rates, quantum yields, and molar absorption coefficients are reported for curcumin in a variety of solutions.

Femtosecond fluorescence upconversion experiments were performed on the naturally occurring medicinal pigment, curcumin, in anionic, cationic, and neutral micelles. In our studies, the micelles are composed of sodium dodecyl sulfate (SDS), dodecyl trimethyl ammonium bromide (DTAB), and triton X-100 (TX-100). We demonstrate that the excited-state kinetics of curcumin in micelles have a fast (3-8 ps) and slow (50-80 ps) component. While deuteration of curcumin has a negligible effect on the fast component, the slow component exhibits a pronounced isotope effect of approximately 1.6, indicating that micelle-captured curcumin undergoes excited-state intramolecular hydrogen atom transfer. Studies of solvation dynamics of curcumin in a 10 ps time window reveal a fast component (< or = 300 fs) followed by a 8, 6, and 3 ps component in the solvation correlation function for the TX-100, DTAB, and SDS micelles, respectively.

Thioflavin T (ThT) dye fluorescence is used regularly to quantify the formation and inhibition of amyloid fibrils in the presence of anti-amyloidogenic compounds such as polyphenols. However, in this study, it was shown, using three polyphenolics (curcumin, quercetin and resveratrol), that ThT fluorescence should be used with caution in the presence of such exogenous compounds. The strong absorptive and fluorescent properties of quercetin and curcumin were found to significantly bias the ThT fluorescence readings in both in situ real-time ThT assays and single time-point dilution ThT-type assays. The presence of curcumin at concentrations as low as 0.01 and 1 mum was sufficient to interfere with the ThT fluorescence associated with fibrillar amyloid-beta(1-42) (0.5 mum) and fibrillar reduced and carboxymethylated kappa-casein (50 mum), respectively. The ThT fluorescence associated with fibrillar amyloid-beta(1-42) was also biased using higher concentrations of resveratrol, a polyphenol that is not spectroscopically active at the wavelengths of ThT fluorescence, implying that there can be direct interactions between ThT and the exogenous compound and/or competitive binding with ThT for the fibrils. Thus, in all cases where ThT is used in the presence of an exogenous compound, biases for amyloid-associated ThT fluorescence should be tested, regardless of whether the additive is spectroscopically active. Simple methods to conduct these tests were described. The Congo red spectral shift assay is demonstrated as a more viable spectrophotometric alternative to ThT, but allied methods, such as transmission electron microscopy, should also be used to assess fibril formation independently of dye-based assays. Structured digital abstract: * MINT-7259867: RCMkappa-CN (uniprotkb:P02668) and RCMkappa-CN (uniprotkb:P02668) bind (MI:0407) by electron microscopy (MI:0040) * MINT-7258930: RCMkappa-CN (uniprotkb:P02668) and RCMkappa-CN (uniprotkb:P02668) bind (MI:0407) by fluorescence technologies (MI:0051) * MINT-7259878: Amyloid beta (uniprotkb:P05067) and Amyloid beta (uniprotkb:P05067) bind (MI:0407) by fluorescence technologies (MI:0051).

The use of curcumin as an effective wound healing agent is of significant interest currently. It is well established that curcumin undergoes rapid degradation in physiological buffer by hydrolysis. The means by which curcumin is stabilized at the wound site to enable healing is poorly understood because blood plasma is composed of approximately 92% water. Plasma proteins, which constitute the remaining 6-8%, has been shown to stabilize curcumin. It is, however, still unclear which proteins are responsible for this phenomenon. In this study, the effects of major plasma proteins, which include human serum albumin (HSA), fibrinogen, immunoglobulin G (IgG), and transferrin, on stabilizing curcumin are investigated. In particular, we investigate their effects on the hydrolysis of curcumin at pH 7.4. In the presence of both transferrin and IgG, curcumin continues to undergo rapid hydrolysis but this reaction is suppressed by the presence of either HSA or fibrinogen with an impressive yield of approximately 95%. Furthermore, the binding constants of curcumin to HSA and fibrinogen are on the order of 10(4) and 10(5) M(-1), respectively. The binding constants of transferrin and IgG, however, are at least 1 order of magnitude less than those of HSA and fibrinogen. The results support that strong binding occurs at the hydrophobic moieties of HSA and fibrinogen, excluding water access. Therefore, strong interactions with HSA and fibrinogen inhibit hydrolysis of curcumin and in turn lead to effective suppression of degradation.

The potential use of the naturally occurring yellow-orange pigment curcumin as a photodynamic therapy agent is one of the most exciting applications of this medicinal compound. Although subnanosecond spectroscopy has been used to investigate the photophysical processes of curcumin, the time resolution is insufficient to detect important and faster photoinduced processes, including solvation and excited-state intramolecular hydrogen atom transfer (ESIHT). In this study, the excited-state photophysics of curcumin is studied by means of ultrafast fluorescence upconversion spectroscopy. The results show two decay components in the excited-state kinetics with time scales of 12-20 ps and approximately 100 ps in methanol and ethylene glycol. The resulting prominent isotope effect in the long component upon deuteration indicates that curcumin undergoes ESIHT in these solvents. The short component (12-20 ps) is insensitive to deuteration, and multiwavelength fluorescence upconversion results show that this decay component is due to solvation of excited-state curcumin.

The ability to quantify changes in cardiomyocyte and myosin volume across gestation and in response to intrauterine insults will lead to a better understanding of the link between low birth weight and an increased risk of heart disease in adult life. We present the use of second-harmonic generation (SHG) and two-photon excitation autofluorescence (TPEF) microscopy to image unstained isolated fetal cardiomyocytes. The simultaneous collection of these two images provides a wealth of information on the morphology of cardiomyocytes. The SHG signal provides high-contrast images of myosin filaments and the TPEF signal can be used to clearly visualize cell morphology. A potential issue may arise if SHG microscopy is performed exclusively due to the lack of sensitivity to distinguish between mononucleated and binucleated cardiomyocytes. However, TPEF microscopy has the ability to efficiently separate the two types of cardiomyocytes. In addition, quantitative analysis of the SHG and TPEF images enables quantification of myosin filament level and accurate determination of cell volume. In short, we demonstrate that advanced nonlinear optical microscopy can be used to answer key physiological questions in the early origins of adult health with increased accuracy and speed compared to previously used methods.

The alkaline hydrolysis of curcumin was studied in three types of micelles composed of the cationic surfactants cetyl trimethylammonium bromide (CTAB) and dodecyl trimethylammonium bromide (DTAB) and the anionic surfactant sodium dodecyl sulfate (SDS). At pH 13, curcumin undergoes rapid degradation by alkaline hydrolysis in the SDS micellar solution. In contrast, alkaline hydrolysis of curcumin is greatly suppressed in the presence of either CTAB or DTAB micelles, with a yield of suppression close to 90%. The results from fluorescence spectroscopic studies reveal that while curcumin remains encapsulated in CTAB and DTAB micelles at pH 13, curcumin is dissociated from the SDS micelles to the aqueous phase at this pH. The absence of encapsulation and stabilization in the SDS micellar solution results in rapid hydrolysis of curcumin.

We introduce an interferometric technique for eliminating the non-resonant background of broadband coherent anti-Stokes Raman scattering (CARS) microscopy. CARS microscopy has been used for imaging a number of biological samples and processes, but the studies are mostly limited to detecting lipids in biological systems by probing the C-H stretch. Non-resonant background and incoherent noise sources can easily overwhelm less intense signals from other molecular vibrations. In this study, we demonstrate a one-laser broadband interferometric technique that separates the spontaneous Raman scattering-related component of the CARS signal from the non-resonant background using liquid benzonitrile as a model system.

Coherent anti-Stokes Raman scattering (CARS) microscopy is emerging as a powerful method for imaging materials and biological systems, partly because of its noninvasiveness and selective chemical sensitivity. However, its full potential for species-selective imaging is limited by a restricted spectral bandwidth. Recent increases in bandwidth are promising but still are not sufficient for the level of robust component discrimination that would be needed in a chemically complex milieu found, for example, in intracellular and extracellular environments. We demonstrate a truly broadband CARS imaging instrument that we use to acquire hyperspectral images with vibrational spectra over a bandwidth of 2500 cm(-1) with a resolution of 13 cm(-1).