Excited State Photophysics of Curcumin and its Modulation in Alkaline Non-Aqueous Medium.

Curcumin, a well-known medicinal pigment, has seen limited applications in biology despite having great potential as a therapeutic drug. Deprotonation is one of the possible ways to enhance solubility of curcumin in polar solvent. Here, we have explored the effect of deprotonation on the ultrafast dynamics of this biomolecule with the help of the time-resolved fluorescence spectroscopic measurements using the femtosecond fluorescence upconversion technique. The excited state photophysics of fully deprotonated curcumin significantly differs from that of neutral curcumin. We have observed that the completely deprotonated curcumin not only has higher quantum yield, but also higher excited state lifetime and slower solvation dynamics in comparison to neutral curcumin. We propose solvation dynamics and intramolecular charge transfer as the excited state processes associated with the radiative decay of the completely deprotonated molecule, while ruling out the possibility of excited state proton exchange or proton transfer. Our results are well supported by time-dependent density-functional theory calculations. Lastly, we have also demonstrated the possibility of modulating the ultrafast dynamics of fully deprotonated curcumin using non-aqueous alkaline binary solvent mixtures. We believe our results will provide significant physical insight towards unveiling the excited state dynamics of this molecule.

Formation of lipid tubules induced by a sugar-like molecule myo-inositol.

The sugar-like molecule myo-inositol (InOH) bears an uncanny structural resemblance to the pyranose form of the sugar D-glucose (DG). InOH and its derivatives play a pivotal role in cell biology; whereby its interaction with the model membrane needs to be studied. Here, we have demonstrated that lipid tubules are formed as a result of the above-said interactions and that these interactions can be prevented by using hydroxyl protected InOH derivatives. We have tried to elucidate the nature of the InOH-membrane interactions by comparing them with DG-membrane interactions and have proposed a mechanism for the same.

Influence of a Polyneurotransmitter on DNA-Mediated Förster-Based Resonance Energy Transfer: A Path Leading to White Light Generation.

The physiologically important biomolecule, dopamine (DA), shows strong self-oxidation and aggregation behaviors, which have been controlled and modulated to result in fluorescent polydopamine (F-PDA) nanoparticles. On the other hand, the simultaneous binding of two diverse deoxyribonucleic acid (DNA) binding probes, 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) and ethidium bromide (EtBr), has been elaborately established to follow the Förster-based resonance energy transfer (FRET) pathway. The comparative understanding of this DNA-mediated FRET in three media, phosphate buffer saline (PBS) of pH 7.4, DA, and F-PDA, has concluded that the FRET efficiency in the three media follows the order: PBS > DA > F-PDA. This controlled FRET in the fluorescent F-PDA matrix serves a pivotal role for efficient white light (WL) generation with excellent Commission Internationale de l'Eclairage (CIE) parameters that match well with that of pure WL emission. The obtained WL emission has been shown to be very specific with respect to concentrations of different participating components and the excitation wavelength of the illuminating source. Furthermore, the optical properties of the WL emitting solution have been observed to be retained excellently inside the well-known agarose gel matrix. Finally, the mechanistic pathway behind such a FRET-based WL generation has been established in detail, and to the best of our knowledge, the current study offers the first and only report that discloses the influence of a fluorescent polyneurotransmitter matrix for successful generation of WL emission.

Phenylalanine Interacts with Oleic Acid-Based Vesicle Membrane. Understanding the Molecular Role of Fibril-Vesicle Interaction under the Context of Phenylketonuria.

In the present contribution, on the basis of a spectroscopic and microscopic investigation, the characterization and photophysics of various assemblies of oleic acid/oleate solution at three pH values, namely, 8.28, 9.72, and 11.77, were explored. The variation in the dynamic response of aqua molecules in and around the assemblies has been interrogated by a picoseconds solvation dynamics experiment using a time-correlated single-photon counting setup employing coumarin-153 as a probe. On the one hand, the time-resolved fluorescence anisotropy measurement along with the fluorescence correlation spectroscopy experiment was executed to extract information regarding the comparison of the extent of the internal restricted confinement of these assemblies. On the other hand, an effort to investigate the cross-interaction between the self-assembled architectures of l-phenylalanine (l-Phe), responsible for phenylketonuria (PKU) disorder, and the oleic acid at the vesicle-forming pH established that the l-Phe fibrillar morphologies strongly alter the dynamic properties of the vesicle membrane formed by the oleic acid. Specifically, the interaction of the l-Phe assemblies with the oleic acid vesicle membrane is found to introduce the flexibility of the vesicle membrane and alter the hydration properties of the membrane. To track the fibril-induced alterations of the oleic acid vesicle properties, various spectroscopic and microscopic investigations were performed. The mutual reconciliation of the experimental outputs, therefore, portrays the state of the art, which accounts for the fibril-induced alterations of the properties of the oleic acid vesicle membrane, the mimicking setup of the cellular membrane, thereby informing us that alterations of such a property of the membrane should be taken into active consideration during the rational development of therapeutic modulators against disorders like PKU.

State of the Art and Perspectives on the Biofunctionalization of Fluorescent Metal Nanoclusters and Carbon Quantum Dots for Targeted Imaging and Drug Delivery.

The interface of nanobio science and cancer nanomedicine is one of the most important current frontiers in research, being full of opportunities and challenges. Ultrasmall fluorescent metal nanoclusters (MNCs) and carbon quantum dots (CQDs) have emerged as promising fluorescent nanomaterials due to their unique physicochemical and optical properties, facile surface functionalization, good photostability, biocompatibility, and aqueous dispersity. These characteristics make them advantageous over conventional fluorophores such as organic dye molecules and semiconductor quantum dots (QDs) for the detection, diagnosis, and treatment of various diseases including cancer. Recently, researchers have focused on the biofunctionalization strategy of the MNCs and CQDs which can tailor their physicochemical and biological properties and, in turn, can empower these biofunctionalized nanoprobes for diverse applications including imaging, drug delivery, theranostics, and other biomedical applications. In this invited feature article, we first discuss some fundamental structural and physicochemical characteristics of the fluorescent biocompatible quantum-sized nanomaterials which have some outstanding features for the development of multiplexed imaging probes, delivery vehicles, and cancer nanomedicine. We then demonstrate the diverse surface engineering of these fluorescent nanomaterials with reactive target specific functional groups which can help to construct multifunctional nanoprobes with improved targeting capabilities having minimal toxicity. The promising future of the biofunctionalized fluorescent quantum-sized nanomaterials in the field of bioanalytical and biomedical research is elaborately demonstrated, showing selected recent works with relevant applications. This invited feature article finally ends with a short discussion of the current challenges and future prospects of the development of these bioconjugated/biofunctionalized nanomaterials to provide insight into this burgeoning field of MNC- and CQD-based diagnostics and therapeutic applications.

Cascade annulative π-extension for the rapid construction of carbazole based polyaromatic hydrocarbons.

A Brønsted acid catalyzed cascade benzannulation strategy for the one-pot synthesis of densely populated poly-aryl benzo[a]carbazole architectures is disclosed from easily affordable fundamental commodities. The efficacy of this technique was further validated via the concise synthesis of structurally unique carbazole based poly-aromatic hydrocarbons. Furthermore, the photo-physical properties of the synthesized compounds are thoroughly investigated.

A Comparative Study on DMSO-Induced Modulation of the Structural and Dynamical Properties of Model Bilayer Membranes.

Modulating the structures and properties of biomembranes via permeation of small amphiphilic molecules is immensely important, having diverse applications in cell biology, biotechnology, and pharmaceuticals, because their physiochemical and biological interactions lead to new pathways for transdermal drug delivery and administration. In this work, we have elucidated the role of dimethyl sulfoxide (DMSO), broadly used as a penetration-enhancing agent and cryoprotective agent on model lipid membranes, using a combination of fluorescence microscopy and time-resolved fluorescence spectroscopy. Spatially resolved fluorescence lifetime imaging microscopy (FLIM) has been employed to unravel how the fluidity of the DMSO-induced bilayer regulates the structural alteration of the vesicles. Moreover, we have also shown that the dehydration effect of DMSO leads to weakening of the hydrogen bond between lipid headgroups and water molecules and results in faster solvation dynamics as demonstrated by femtosecond time-resolved fluorescence spectroscopy. It has been gleaned that the water dynamics becomes faster because bilayer rigidity decreases in the presence of DMSO, which is also supported by time-resolved rotational anisotropy measurements. The enhanced diffusivity and increased membrane fluidity in the presence of DMSO are further ratified at the single-molecule level through fluorescence correlation spectroscopy (FCS) measurements. Our results indicate that while the presence of DMSO significantly affects the 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-rac-glycero-3-phosphatidylcholine (DPPC) bilayers, it has a weak effect on 1,2-dimyristoyl-sn-glycero-3-phospho-rac-glycerol (DMPG) vesicles, which might explain the preferential interaction of DMSO with the positively charged choline group present in DMPC and DPPC vesicles. The experimental findings have also been further verified with molecular dynamics simulation studies. Moreover, it has been observed that DMSO is likely to have a differential effect on heterogeneous bilayer membranes depending on the structure and composition of their headgroups. Our results illuminate the importance of probing the lipid structure and composition of cellular membranes in determining the effects of cryoprotective agents.

Aging-Dependent Morphological Crystallinity Determines Membrane Activity of l-Phenylalanine Self-Assembles.

Amyloid polymorphism has emerged as an important topic of research in recent years to identify the particular species responsible for several neurodegenerative disorders, whereas the concept is overlooked in the case of the simplest building block, that is, l-phenylalanine (l-Phe) self-assembly. Here, we report the first evidence of l-Phe polymorphism and the conversion of metastable helical fibrillar to thermodynamically stable rodlike crystalline morphologies with increasing time and temperature. Furthermore, only the fibrillar l-Phe polymorph shows a significant modulation of the model membrane. In addition, the l-Phe molecules prefer to arrange in a multilayered rodlike fashion than in a lateral arrangement, which reduces the membrane binding ability of the l-Phe polymorph due to the decrease in the partial charge of the N-terminal of l-Phe units. The present work exemplifies a different approach to understanding l-Phe self-assembly and provides an effective strategy for the therapy of phenylketonuria by scrutinizing the discrete membrane activity of different l-Phe polymorphs.

Denaturant-Mediated Modulation of the Formation and Drug Encapsulation Responses of Gold Nanoparticles.

The extensive and diversified applications of the well-known plasmonic nanoparticle systems along with their easy and environment-friendly synthesis strategies drive us to investigate in-depth this important research field. In the current scenario, our present study deals with an important plasmonic nanomaterial, i.e., globular protein, and human serum albumin (HSA)-conjugated gold nanoparticle (HSA-Au NP) system. The well-known chemical denaturants, urea and guanidine hydrochloride (GdnHCl or GnHCl), are investigated to show detrimental effects toward the formation of gold nanoparticles; however, the effect of GdnHCl is observed to be much prominent compared to that of urea. The synthesized nanoparticle system is found to be highly biocompatible from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based cytotoxicity assay, and therefore, the applications of encapsulation of the well-known anticancer drug molecule, doxorubicin hydrochloride (Dox), in the nanoparticle system are further studied. In this drug encapsulation study, drug-metal complexation between Dox and HAuCl4·3H2O has been discussed elaborately. Similar to the nanoparticle formation, the effects of denaturants on drug encapsulation have also been discovered, and interestingly, it has been observed that urea plays a positive role, whereas GdnHCl plays a negative or detrimental role toward drug encapsulation in the synthesized gold nanoparticle system. The detailed photophysical mechanisms behind the drug encapsulation in the synthesized plasmonic nanosystem at every stage have also been explored. Overall, this study will conclusively explain the influences of the extensively used chemical denaturants on the synthesis and drug encapsulation behaviors of a well-known protein-conjugated gold nanoparticle, and as a consequence, it can be highly useful and acceptable to the biomedical and pharmaceutical research communities.

Antagonist Effects of l-Phenylalanine and the Enantiomeric Mixture Containing d-Phenylalanine on Phospholipid Vesicle Membrane.

One of the congenital flaws of metabolism, phenylketonuria (PKU), is known to be related to the self-assembly of toxic fibrillar aggregates of phenylalanine (Phe) in blood at elevated concentrations. Our experimental findings using l-phenylalanine (l-Phe) at millimolar concentration suggest the formation of fibrillar morphologies in the dry phase, which in the solution phase interact strongly with the model membrane composed of 1,2-diacyl-sn-glycero-phosphocholine (LAPC) lipid, thereby decreasing the rigidity (or increasing the fluidity) of the membrane. The hydrophobic interaction, in addition to the electrostatic attraction of Phe with the model membrane, is found to be responsible for such phenomena. On the contrary, various microscopic observations reveal that such fibrillar morphologies of l-Phe are severely ruptured in the presence of its enantiomer d-phenylalanine (d-Phe), thereby converting the fibrillar morphologies into crushed flakes. Various biophysical studies, including the solvation dynamics experiment, suggest that this l-Phe in the presence of d-Phe, when interacting with the same model membrane, now reverts the rigidity of the membrane, i.e., increases the rigidity of the membrane, which was lost due to interaction with l-Phe exclusively. Fluorescence anisotropy measurements also support this reverse rigid character of the membrane in the presence of an enantiomeric mixture of amino acids. A comprehensive understanding of the interaction of Phe with the model membrane is further pursued at the single-molecular fluorescence detection level using fluorescence correlation spectroscopy (FCS) experiments. Therefore, our experimental conclusion interprets a linear correlation between increased permeability and enhanced fluidity of the membrane in the presence of l-Phe and certifies d-Phe as a therapeutic modulator of l-Phe fibrillar morphologies. Further, the study proposes that the rigidity of the membrane lost due to interaction with l-Phe was reinstated-in fact, increased-in the presence of the enantiomeric mixture containing both d- and l-Phe.

Selective Self-Assembly of 5-Fluorouracil through Nonlinear Solvent Response Modulates Membrane Dynamics.

Controllable self-assembly and understanding of the interaction between single metabolite fibrils and live-cell membranes have paramount importance in providing minimal treatment in several neurodegenerative disorders. Here, utilizing the nonlinear nature and peculiar hydrogen bonding behavior of the dimethyl sulfoxide (DMSO)-water mixture, the selective self-assembly of a single metabolite 5-fluorouracil (5-FU) is achieved. A direct correlation between water availability and selective self-assembly of 5-FU is ratified from the excited-state dynamics. The specific fibrillar structures of 5-FU exhibit a great potential to modulate live cell membrane fluidity and model membrane lipid distribution. After 5-FU fibril addition, a disorder of H-bonded water molecules arises several layers beyond the first hydration shell of the polar headgroups, which essentially modifies interfacial water structure and dynamics. Overall, our results shed light on the role of solvent to govern specific self-assembly and also lay the foundation accounting for the earlier stage of several diseases and multidrug resistance.

Surface Ligand-Controlled Wavelength-Tunable Luminescence of Gold Nanoclusters: Cellular Imaging and Smart Fluorescent Probes for Amyloid Detection.

Gold nanoclusters (Au NCs) are an emerging class of fluorescent nanomaterials due to their fascinating chemical or physical properties and atomically precise structures; hence, they have been widely used in the field of biosensing and bioimaging. In this article, we demonstrate the green synthesis of orange, yellow, green, and cyan emitting Au NCs by core etching and ligand exchange methodology. Our investigation reveals that the chain length of the mercaptan acids, which are present on the surface of the Au NCs, controls the optical and electronic properties of the synthesized NCs. The steady-state and time-resolved spectroscopic data suggest that the emission properties of Au NCs mainly originate from the ligand to metal charge transfer (LMCT) transition. Alterations of the optical properties of these Au NCs can be proposed due to the difference in the core size of the Au NCs, which is strongly influenced by the surface-capping ligands. These NCs are highly biocompatible and nontoxic as evidenced by the cell viability and cellular uptake studies. By virtue of this, our as-synthesized NCs have been successfully used as excellent intracellular fluorescent imaging probes. Interestingly, fluorescence properties of Au NCs can efficiently probe the protein amyloids associated with several neurodegenerative diseases. To facilitate research in the field of amyloidosis, we have demonstrated fluorescence lifetime imaging microscopy (FLIM) and fluorescence correlation spectroscopy (FCS) as two advanced tools to probe the aggregation of proteins and to monitor the physical interactions between proteins and NCs. It has been observed that the hydrophobicity of the NC surface can trigger the amyloid detection capability of Au NCs. Owing to these unique optical and attractive biological properties coupled with the imaging capability, these ultrasmall-sized Au NCs may enable in vivo detection of amyloids in the near future.

Insight into the Dynamics of Different Fluorophores in the Interior of Aerosol OT Lamellar Structures in the Presence of Sugars: From Picosecond-to-Femtosecond Study.

It is well reported that sugar molecules provide different types of stabilization to biomembranes both in vitro as well as in vivo. In the present article, our focus is to investigate the interactions of two sugar molecules (sucrose and sucralose) with the lamellar structures of aerosol OT (AOT). We have attempted the structural characterization of the lamellae in the presence and absence of sugars with the aid of dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), Fourier transformed infrared spectroscopy (FTIR), polarized optical microscopy (POM), and cryogenic-transmission electron microscopic (cryo-TEM) techniques. In this study, we have chosen three Coumarin dyes, which show a wide variation of hydrophobicity and performed a combination of steady-state and time-resolved fluorescence measurements to unveil the inner detail of the location of the sugars and their specific interactions with the lamellar structures. Our study reveals that sucrose molecules are present in the interfacial region with a major population whereas the most probable location of sucralose is the interior of the AOT bilayer. Therefore, sucralose molecules probably penetrate the bilayer by decreasing the efficient packing of AOT. The important essence of this study is the location and the interactions of sucralose with the lamellae which may provide a future direction to the transportation of the drug molecules in the biomembrane.