Microviscosity-Assisted Disaggregation of a Model Ophthalmic Drug and FRET-Controlled Singlet Oxygen Generation in Lyotropic Liquid Crystals.

Different phases of lyotropic liquid crystals (LLCs), made up of mesogen-like sodium dodecyl sulfate (SDS), mainly bestow different bulk viscosities. Along with this, the role of microviscosities of the individual LLC phases is of immense interest because a minute change in it due to guest incorporation can cause significant alteration in their property as a potential energy transfer scaffold. Recently, LLCs have been identified as plausible drug delivery agents for ocular treatments. In this direction, the present work illustrates photophysical modulations of an important laser dye as well as an ophthalmic medicine, coumarin 6 (C6), inside different LLC phases in an aqueous medium. C6 molecules spontaneously accumulate in water, leading to aggregation-caused quenching (ACQ) of fluorescence. However, the different phases of the LLCs prepared from SDS and water helped in disintegrating the C6 colonies to various extents depending upon the microviscosity. The heterogeneity in the LLC phases, in turn, could modulate the Förster resonance energy transfer (FRET) between C6 and the LLC incorporated with N-doped carbon nanoparticles (N-CNPs). The N-CNPs act as potential photosensitizers and generate singlet oxygen (1O2), a reactive oxygen species (ROS), to different extents. Microviscosities of the prepared LLCs were calculated by using fluorescence correlation spectroscopy (FCS). The different phases of the LLCs, viz., lamellar and hexagonal, with different microviscosities controlled the extent of C6 disaggregation and hence the FRET and the ROS generation. The results are encouraging since ROS generation has a significant role in the vision mechanism and PDT-based applications. LLC-based drug administration with potential FRET to control ROS generation may become handy in ophthalmology. The LLC phases used in this experiment not only served the purpose of drug delivery but also the photophysical events therein are compatible with the ocular environment.

Capturing the Interplay Between TADF and RTP Through Mechanically Flexible Polymorphic Optical Waveguides.

Polymorphism plays a pivotal role in generating a range of crystalline materials with diverse photophysical and mechanical attributes, all originating from the same molecule. Here, we showcase two distinct polymorphs: green (GY) emissive and orange (OR) emissive crystals of 5'-(4-(diphenylamino)phenyl)-[2,2'-bithiophene]-5-carbaldehyde (TPA-CHO). These polymorphs display differing optical characteristics, with GY exhibiting thermally activated delayed fluorescence (TADF) and OR showing room temperature phosphorescence (RTP). Additionally, both polymorphic crystals display mechanical flexibility and optical waveguiding capabilities. Leveraging the AFM-tip-based mechanophotonics technique, we position the GY optical waveguide at varying lengths perpendicular to the OR waveguide. This approach facilitates the exploration of the interplay between TADF and RTP phenomena by judiciously controlling the optical path length of crystal waveguides. Essentially, our approach provides a clear pathway for understanding and controlling the photophysical processes in organic molecular crystals, paving the way for advancements in polymorphic crystal-based photonic circuit technologies.

Achieving the Reverse Intersystem Crossing in Chalcone Based Donor-Acceptor System through Down-Conversion of Triplet Exciton.

In recent years, understanding the mechanism of thermally activated delayed fluorescence (TADF) has become the primary choice for designing high-efficiency, low-cost, metal-free organic light emitting diodes (OLEDs). Herein, we propose a strategically designed chalcone based donor-acceptor system, where intensification of delayed fluorescence with decrease in temperature (300 K to 100 K) is observed; the theoretical investigations of electronic states and orbital characters uncovered a new cold rISC pathway in donor-acceptor system, where rISC occurs through the down-conversation of higher triplet exciton (from T3 ) to lowest singlet state (S1 ), having negative energy splitting, thus no thermal energy is required. The comprehensive research described herein might open-up new avenues in donor-acceptor system over the conventional up-convention of triplet exciton and demonstrates that not necessarily all delayed fluorescence are thermally activated (TADF).

A Curated Graphene Quantum Dot-Porphyrin-Based Photosensitizer for Effective Singlet Oxygen Generation through Energy Transfer.

Porphyrin-based photosensitizers are proven generators of reactive oxygen species (ROS), such as singlet oxygen, and used as anti-cancer therapeutic agents. However, most of these compounds suffer from potential drawbacks due to limited photostability, hydrophobicity, aggregation propensity, and low cellular uptake. Ultrasmall fluorescent graphene quantum dots (GQDs) have emerged as the next-generation carriers for drugs and have gained reputation in the pharmaceutical domain. Considering the various limiting factors in porphyrin-based ROS generation and cellular internalization, here, we have developed a method to generate tetrakis(m-nitrophenyl) porphyrin (TNPP)-GQD exciplexes. This allows resonance energy transfer (RET) from GQDs to TNPP. The calculated overlap integrals for GQD-TNPP and AGQD-TNPP (1.001 × 1018 and 1.257 × 1017 M-1 cm-1 nm4, respectively) assured 95 and 71% energy transfer. The optimum donor-acceptor distances in these couples are 59.82 and 62.65 Å, respectively, which yielded the rate constant of RET as 4.09 and 0.56 ns-1, respectively. The efficient RET helped in subsequent generation of singlet oxygen. The singlet oxygen quantum yields (SOQY) of around 0.435 and 0.464 for GQD-TNPP and AGQD-TNPP, respectively, are comparable to those of different porphyrin derivatives where the SOQY ranges from 0.55 to 0.70 when used with Triton X-100. The data show that non-conjugated amine- and amide-functionalized GQDs (AGQDs) are better candidates in this case because of the special properties of the amine groups. The systems could be excited at 450 nm for FRET, which favors biological usage.

Events at the Interface: How Do Interfaces Modulate the Dynamics and Functionalities of Guest Molecules?

Chemical and biological interfaces are of various types, which could be between two materials of the same and/or different states, two phases of the same material, biological substrates and the outer environment, surfactant or polymeric membranes and the bulk, and so forth. Small-molecule guests frequently interact with such interfaces that decide their functionalities. The structural and behavioral properties undergo considerable characteristic changes, which control their final course of action in the targeted application. This Perspective will discuss mainly the chemical interfaces constituted by the surfactants, polymers, lipids, and nucleic acids and their impacts on the dynamics of small-molecule guests. Some specific and interesting phenomena and future prospects will be elucidated in this Perspective.

Impact of cationic surfactant-induced DNA compaction on the characteristics of a minor groove bound flavonol.

3-Hydroxyflavone (3-HF), which binds to the minor groove of DNA, is a strong antioxidant and hence a potent therapeutic and diagnostic agent. A special photo-property, called excited state intramolecular proton transfer (ESIPT), makes the 3-HF derivatives sensitive to the cellular hydrophobic microenvironment. The present study depicts the various changes in the ESIPT of 3-HF due to cationic surfactant-induced compaction of DNA.

Biocompatible and optically stable hydrophobic fluorescent carbon dots for isolation and imaging of lipid rafts in model membrane.

Lateral heterogeneity in cell membranes features a variety of compositions that influence their inherent properties. One such biophysical variation is the formation of a membrane or lipid raft, which plays important roles in many cellular processes. The lipid rafts on the cell membrane are mostly identified by specific dyes and heavy metal quantum dots, which have their own drawbacks, such as cytotoxicity, photostability, and incompatibility. To this end, we synthesized special, hydrophobic, fluorescent, photostable, and non-cytotoxic carbon dots (CDs) by solvent-free thermal treatment using non-cytotoxic materials and incorporated into the lipid bilayers of giant unilamellar vesicles (GUVs) made from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and dipalmitoylphosphatidylcholine (DPPC) lipids. A 2:2:1 mixture of DOPC, DPPC, and cholesterol (Chol) develops lipid rafts on the membrane by phase separation. The photophysical properties of the CDs get modulated on incorporation into the lipid rafts that identifies the membrane heterogeneity. The main attempt in this work is to develop a new, simple, cost-effective, and bio-friendly lipid raft marker, which can be used in biological applications, alongside other conventional raft markers, with more advantages.

Photosensitization Dynamics of Stable Copper Nanoclusters inside the Aqueous Core of Reverse Micelles with Different Pool Sizes.

The perennial problem of instability of fluorescent copper nanoclusters (Cu NCs), stemming principally from aerial oxidation, has prevented their vivid usage in energy harvesting compared to the other metal NCs. However, replacement of the much expensive metal NCs with the cheaper Cu NCs is desirable if the functions are met with. Although thiolate protection of Cu NCs could bring some stability to them, appreciably decentlystable Cu NCs were produced inside the aqueous core of reverse micelles (RMs). However, this recent development has not been further explored on the photosensitization of the Cu NCs inside the RMs and their controlled modulation as energy antenna. Here we have synthesized stable Cu NCs inside the aqueous core of RMs with three different pool sizes and established photoinduced electron transfer (PET) to an electron acceptor. Considering the bulk quencher concentration, it appears that the extent of PET increases with decrease in the size of the aqueous core of RMs. However, calculating the effective concentration of the electron acceptor inside the RMs and considering the polarity of the microheterogeneous systems, it becomes clear that the extent of PET actually decreases with decrease in the size of the aqueous pool (w0, i.e., [H2O]/[AOT]) = 5-20) in the RMs. This proof of concept and the results are promising toward applications in PET-driven phenomena such as solar cells or batteries.

Doping Dopamine in Carbon Nanoparticles: A New Multifunctional Logic-Based Decision-Making Molecule.

A dopamine-functionalized carbon nanoparticle (CNP)-based platform is designed to reversibly control the optical signal, leading to a multifunctional logic system regulated by pH and light. pH-regulated unique reversible transformation of oxidized and reduced forms of a neurotransmitter, dopamine, conjugated with CNPs plays a decisive role in capturing the final output of the logic function. Inspired by this phenomenon, herein, we report the use of dopamine-docked CNPs to construct different molecular logic gates with an intention to develop the next-generation molecular logic gates. We could successfully construct two basic molecular logic gates, namely, YES and NOT, using one input; two modular logic gates; an IMPLICATION logic gate using two inputs; and finally a combination of OR and AND gates using three inputs. The optical response of the synthesized NP conjugate provides a fluorescence-based "Erase-Read-Write-Read" function. The proposed phenomenon may open a new concept of biochemical logic gates with fluorescence output for neuronal imaging.

Surfactant and Cyclodextrin Induced Vesicle to Micelle to Vesicle Transformation in Aqueous Medium.

The physicochemical behavior and characteristics of lipid vesicles and micelles in aqueous medium are greatly tuned by changing the ambient physical parameters, such as temperature, pH, and ionic strength. The process is also controlled by external additives and the nature of the surfactants. In this work, we have used water-soluble surfactant and cyclodextrin to transform lipid vesicles to micelles to vesicles without changing the physical ambience. In this regard, we have used a special pyrene-tagged guest compound that readily forms excimer in water and thus acts as a reporter for the process. Giant lipid vesicles (biological cell mimics) are disrupted by cationic surfactants to form mixed elongated micelles that transform to vesicles on applying a cyclodextrin host.

A Fluorescence Lifetime Imaging Microscopy Supported Investigation on Temperature-Dependent Penetration of Dopamine in a 1,2-Ditetradecanoyl-sn-glycero-3-phospho-(1'-rac-glycerol) Lipid Bilayer.

Distribution of dopamine, an essential neurotransmitter in mammalian central and peripheral nervous systems, in a lipid bilayer and at the surface of 1,2-ditetradecanoyl-sn-glycero-3-phospho-(1'-rac-glycerol) vesicles has been studied herein. To track the progress of dopamine through different regions of the lipid vesicle, these were synthesized using 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-labeled phospholipid molecules tagged to either the headgroup (NBDPE) or the acyl chain (NBDPG). Dopamine-induced quenching of NBD fluorescence in the lipid vesicles demonstrates that dopamine has a preference to diffuse into the lipid bilayer. The change in the excited state lifetime obtained for NBDPG clearly indicates the preference in dopamine binding. The propositions were supported by fluorescence lifetime imaging microscopy.

Revival of the nearly extinct fluorescence of coumarin 6 in water and complete transfer of energy to rhodamine 123.

The nearly extinct fluorescence of coumarin 6 in water due to microcrystal formation is revived by micelles. Practically complete transfer of energy from coumarin 6 to rhodamine 123 through resonance energy transfer could be achieved.

NIR-emitting chiral gold nanoclusters coated with γ-cyclodextrin are pH sensitive: Application as biomarker.

Change in cellular pH due to onset of certain malfunctions needs to be tracked quickly so that treatment to cure such incidents may be started immediately. For example, microenvironment of a developing tumor is acidic due to high metabolic rate as well as low oxygen supply. Hence biomarkers that can sharply sense transition in pH could be of great use in the early detection of tumor formation. In the present work, a unique pH sensitive non-cytotoxic gold nanocluster based probe has been synthesized to precisely detect sharp change in biological pH. The gold nanoclusters were coated with dihydrolipoic acid incorporated γ-cyclodextrins. Measurements with steady state fluorometric changes reveal the sensibility of the probes through obvious wavelength shift depending on the changes in the microenvironment. The nanocluster based probe has been successfully applied to detect cancer cells with high precision. FROM THE CLINICAL EDITOR: Biomarkers sensitive to physiological environment have extensive uses in nanomedicines. pH sensitive ultrasmall gold nanoclusters coated with dihydrolipoic acid incorporated γ-cyclodextrins indicate Changes in cellular pH, therefore certain malfunctions. The new biomarker could be useful to detect tumor calls.

Promoting the "water-wire" mechanism of double proton transfer in [2,2'-bipyridyl]-3,3'-diol by porous gold nanoparticles.

The effect of nanopores in porous gold nanoparticles (Au NPs) on excited-state double proton transfer (DPT) in [2,2'-bipyridyl]-3,3'-diol (BP(OH)2) in an aqueous environment is the main focus of the present work. DPT in BP(OH)2 is known to take place through two mechanisms. In a bulk environment, an open solvated molecule facilitates the process and emits at 460 nm whereas, in a confined situation, formation of a "water wire" between the prototropic centers leads to the transfer of protons. It has been shown spectroscopically in the present study that in the nanovessels provided by nanoporous Au NPs, the unconventional mechanism of DPT through the formation of a "water wire" is promoted due to the presence of a limited number of water molecules around the probe. Experiments in the presence of solid pure Au, Ag and Au/Ag NPs were performed to support our proposition. Time-resolved fluorescence spectral changes confirm our findings.

Fluorescent metal nanoclusters: prospects for photoinduced electron transfer and energy harvesting.

Research on noble metal nanoclusters (MNCs) (elements with filled electron d-bands) is progressing forward because of the extensive and extraordinary chemical, optical, and physical properties of these materials. Because of the ultrasmall size of the MNCs (typically within 1-3 nm), they can be applied in areas of nearly all possible scientific domains. The greatest advantage of MNCs is the tunability that can be imposed, not only on their structures, but also on their chemical, physical, and biological properties. Nowadays, MNCs are very effectively used as energy donors and acceptors under suitable conditions and hence act as energy harvesters in solar cells, semiconductors, and biomarkers. In addition, ultrafast photoinduced electron transfer (PET) can be practised using MNCs under various circumstances. Herein, we have focused on the energy harvesting phenomena of Au-, Ag-, and Cu-based MNCs and elaborated on different ways to apply them.

Hydrophobic Chain-Induced Conversion of Three-Dimensional Perovskite Nanocrystals to Gold Nanocluster-Grafted Two-Dimensional Platelets for Photoinduced Electron Transfer Substrate Formulation.

Considering the augmentation of new generation energy harvesting devices and applications of electron-hole separation therein, conversion of 3D cubic CsPbBr3 perovskite nanocrystals into 2D-platelets through ligand-ligand hydrophobic interactions has been conceived here. Cationic surfactants with various chain length coated the gold nanoclusters (AuNCs) that interact with oleic acid (OA) and oleylamine (OAm) coated 3D CsPbBr3 nanocrystals to disintegrate the crystallinity of the perovskites and reformation of AuNC-grafted 2D-platelets of unusually large size. The planar perovskite-derivatives act as an exciton donor to the embedded AuNCs through photoinduced electron transfer (PET). This process is controlled by the optimum surfactant chain length. Transient absorption spectroscopy shows that the fastest radical growth time (4 ps) was with the 14-carbon containing tail of the surfactant, followed by the 16-carbon (45 ps) and the 12-carbon (290 ps) ones. PET is administered by the energy gaps of the participating candidates that control the transition dynamics. Our findings can be a potential tool to develop metal nanocluster-based hybrid 2D perovskite-derived platelets for optoelectronic applications.

Physicochemical perspective of cyclodextrin nano and microaggregates.

''Chemistry beyond the molecule'' is the nickname for supramolecular chemistry. This branch of study is based on molecular recognition that is host-guest chemistry. A number of potential hosts have been defined and applied in scores of studies. Among all potential hosts, cyclodextrins occupy a high position due to their characteristic solubilisation capability and biocompatibility. In the present article we are revisiting the host-guest aspects of cyclodextrins from a physicochemical perspective. We present details of formation and applications of cyclodextrin nanoaggregates induced by guest molecules, the concerned thermodynamics behind the process and also the effect of concentration of the guest molecules on the morphology of the aggregates. This article reviews the topic mainly from the spectroscopic point of view.

"Extra stabilisation" of a pyrene based molecular couple by γ-cyclodextrin in the excited electronic state.

Two thiosemicarbazide and semicarbazide functionalized pyrene labeled Schiff base compounds have been synthesized. The pyrene moieties in the compounds result in formation of π-π coupled complexes in aqueous medium in the excited electronic state. Added γ-cyclodextrin allows incorporation of the pyrene head inside its less polar core and promotes hydrogen bonding of the thio and oxo groups of the compounds with its rim hydroxyl groups to "stabilise" the monomers. This is confirmed by FT-IR and absorption spectroscopy. The stabilised monomers lead to formation of stabilised excimers as monitored by steady state and time-resolved fluorescence spectroscopy through varying the experimental conditions. The proposed model for the stabilisation of the Schiff base monomers has been evidenced by comparing with the fluorescence spectroscopic changes of two control compounds. The present work reports a step ahead toward proposing a simple host-guest method to extra stabilise the pyrene based excimers that can be biologically utilised.

Graphene Quantum Dot Assisted Translocation of Daunomycin through an Ordered Lipid Membrane: A Study by Fluorescence Lifetime Imaging Microscopy and Resonance Energy Transfer.

Daunomycin (DN) is a well-known chemotherapy drug frequently used in treating acute myeloid and lymphoblastic leukemia. It needs to be delivered to the therapeutic target by a delivering agent that beats the blood-brain barrier. DN is known to be specifically located at the membrane surface and scantly to the bilayer. Penetration of DN into the membrane bilayer depends on the molecular packing of the lipid. It does not travel promptly to the interior of the cells and needs a carrier to serve the purpose. Here, we have demonstrated, by fluorescence lifetime imaging spectroscopy (FLIM) and resonance energy transfer (RET) phenomenon, that ultrasmall graphene quantum dots (GQDs) can be internalized into the aqueous pool of giant unilamellar vesicles (GUVs) made from dipalmitoylphosphatidylcholine (DPPC) lipids, which, in turn, help in fast translocation of DN through the membrane without any delivery vehicle.

Development of a carbon dot and methylene blue NIR-emitting FLIM-FRET pair in niosomes for controlled ROS generation.

Non-ionic surfactant vesicular systems (niosomes) are structurally similar to lipid vesicles, differing only in the bilayer composition. Herein we report a unique method to generate reactive oxygen species (ROS) utilizing a FLIM-FRET technique involving niosome-trapped yellow emissive carbon dots (YCDs) and methylene blue (MB) in aqueous medium under neutral conditions. Niosomes are biologically important because of their good stability and extremely low toxicity. Fluorescent CDs, emitting in the higher wavelengths on visible light excitation, are of incredible importance in bio-imaging and optoelectronics. Hence, we prepared nitrogen-containing YCDs from a single precursor, o-phenylenediamine, and explained their detailed photophysics upon incorporation into the niosomal bilayer. The YCDs are polarity sensitive, and are rotationally restricted in niosomes, which increases their fluorescence quantum yield from 29% (in water) to 91%. These YCDs are tactically employed to develop a near infrared (NIR) FRET pair with methylene blue (MB), which is a very well-known type-I and type-II photosensitizer. This FRET pair, which emits in the NIR region, is found to be an ideal system to generate ROS by excitation in the lower visible wavelengths. Interestingly, the ROS production by MB from the dissolved oxygen is enhanced inside the niosomes. The donor and the acceptor moieties in this unique NIR-emitting FRET pair display an unprecedented 300 nm Stokes shift. The findings could be influential in bio-imaging in the NIR region evading cellular autofluorescence and the controllably generated ROS can be further applied as a potential photodynamic therapeutic agent.