Ultrafast Dynamics of the Medicinal Pigment Curcumin inside the Imidazolium Surface Active Ionic Liquid Containing Giant Vesicles and White Light Generation via Triple-FRET Technique.

The naturally occurring yellow polyphenolic medicinal pigment curcumin shows ultrafast dynamics in the excited states. These ultrafast dynamics are strongly influenced by the rigidity of the environments of the systems. The present investigation unveils the ultrafast excited-state intramolecular hydrogen atom transfer (ESIHT) (which is involved in the antioxidant mechanism) and the solvation dynamics of curcumin inside the imidazolium surface active ionic liquid (SAIL), 1-hexadecyl-3-methylimidazolium chloride ([C16mim]Cl) micelle, and giant vesicles after introducing sorbitan monoesters (Span 20 and Span 80) in the aqueous medium. Interestingly, the short hydrocarbon chain containing Span 20 forms smaller, less rigid vesicles, and the long hydrocarbon chain containing Span 80 forms larger, more rigid giant vesicles after being assembled with [C16mim]Cl. The ESIHT and the solvation dynamics are slower in Span 80, containing rigid vesicles, than that in Span 20, comprising less rigid vesicles. Finally, we have established a three-component fluorescence resonance energy transfer (Triple-FRET) system to generate white light (WL) in the micelle and giant vesicles. Here the hydrophobic dye 1,6-diphenyl-1,3,5-hexatriene (DPH) acts as the donor, and the hydrophilic anticancer drug doxorubicin hydrochloride (DOX) serves as the acceptor along with the intermediate donor, curcumin. At a specific combination of the concentrations of these dyes in a particular self-assembled system, WL is generated due to the triple-FRET phenomena.

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.

Insights into the Strong Emission Enhancement of Molecular Rotor Thioflavin T in Aqueous Cellulose Nanocrystal Dispersion: White Light Generation in Protein and Micellar Media.

Thioflavin t (THT) is a well-known molecular rotor extensively used to detect amyloid-like structures. But THT shows very weak emission in water. In this article, we have found that THT shows very strong emission in the presence of cellulose nanocrystals (CNCs). Steady-state and time-resolved emission techniques have been used to study the strong emission of THT in aqueous CNC dispersion. The time-resolved study showed that in the presence of CNCs, the lifetime increased by ∼1500 fold compared to pure water (<1 ps). To know the nature of interaction and also the reason for this increase in emission zeta potential, stimuli-dependent and temperature-dependent studies have been carried out. These studies proposed that electrostatic interaction is the main factor for this binding of THT with CNCs. Further, the addition of another anionic lipophilic dye, merocyanine 540 (MC540), with CNCs-THT in both BSA protein (CIE: 0.33, 0.32) and TX-100 micellar (4.5 mM) (CIE: 0.32, 0.30) solutions produced excellent white light emission. Lifetime decay and absorption studies proposed a possible fluorescence resonance energy transfer mechanism in this generation of white light emission.

Targeting genomic DNAs and oligonucleotide on base specificity: A comparative spectroscopic, computational and in vitro study.

Drug discovery in targeted nucleic acid therapeutics encompass several stages and rigorous challenges owing to less specificity of the DNA binders and high failure rate in different stages of clinical trials. In this perspective, we report newly synthesized ethyl 4-(pyrrolo[1,2-a]quinolin-4-yl)benzoate (PQN) with minor groove A-T base pair binding selectivity and encouraging in cell results. This pyrrolo quinolin derivative has shown excellent groove binding ability with three of our inspected genomic DNAs (cpDNA 73 % AT, ctDNA58% AT and mlDNA 28 % AT) with varying A-T and G-C content. Notably in spite of similar binding patterns PQN have strong binding preference with A-T rich groove of genomic cpDNA over the ctDNA and mlDNA. Spectroscopic experiments like steady state absorption and emission results have established the relative binding strengths (Kabs = 6.3 × 105 M-1, 5.6 × 104 M-1, 4.3 × 104 M-1 and Kemiss = 6.1 × 105 M-1, 5.7 × 104 M-1 and 3.5 × 104 M-1 for PQN-cpDNA, PQN-ctDNA and PQN-mlDNA respectively) whereas circular dichroism and thermal melting studies have unveiled the groove binding mechanism. Specific A-T base pair attachment with van der Waals interaction and quantitative hydrogen bonding assessment were characterized by computational modeling. In addition to genomic DNAs, preferential A-T base pair binding in minor groove was also observed with our designed and synthesized deca-nucleotide (primer sequences 5/-GCGAATTCGC-3/ and 3/-CGCTTAAGCG-5/). Cell viability assays (86.13 % in 6.58 µM and 84.01 % in 9.88 µM concentrations) and confocal microscopy revealed low cytotoxicity (IC50 25.86 µM) and efficient perinuclear localization of PQN. We propose PQN with excellent DNA-minor groove binding capacity and intracellular permeation properties, as a lead for further studies encompassing nucleic acid therapeutics.

Deciphering Dual Modes of Parkinsonian Biomolecules Derived Fluorescent Nanoparticles: Protein Specificity and White Light Generation.

Dopamine (DA) and 3,4-dihydroxy-l-phenylalanine (L-Dopa or DPA), a marker and medicine for the neurological disorder Parkinson's disease (PD), lead to the formation of polymeric fluorescent nanoparticles (F-Poly NPs or F-NPs or simply, NPs). The interaction study between proteins and NPs shows prominent interaction with strong specificity toward albumin type proteins for DPA derived and mixed NPs. Furthermore, encapsulation of the anticancer drug doxorubicin hydrochloride (Dox) inside the NP-protein conjugates results in excellent white light emission with pronounced specificity toward albumin proteins for F-PDPA and F-Mix NPs. Finally, the use of BSA protein fibril resulting in strong binding with NPs along with Dox assisted white light emission has also been studied.

Amyloids Formed by Nonaromatic Amino Acid Methionine and Its Cross with Phenylalanine Significantly Affects Phospholipid Vesicle Membrane: An Insight into Hypermethioninemia Disorder.

The incorrect metabolic breakdown of the nonaromatic amino acid methionine (Met) leads to the disorder called hypermethioninemia via an unknown mechanism. To understand the molecular level pathogenesis of this disorder, we prepared a DMPC lipid membrane, the mimicking setup of the cell membrane, and explored the effect of the millimolar level of Met on it. We found that Met forms toxic fibrillar aggregates that disrupt the rigidity of the membrane bilayer, and increases the dynamic response of water molecules surrounding the membrane as well as the heterogeneity of the membrane. Such aggregates strongly deform red blood cells. This opens the requirement to consider therapeutic antagonists either to resist or to inhibit the toxic amyloid aggregates against hypermethioninemia. Moreover, such disrupting effect on membrane bilayer and cytotoxicity along with deformation effect on RBC by the cross amyloids of Met and Phenylalanine (Phe) was found to be most virulent. This exclusive observation of the enhanced virulent effect of the cross amyloids is expected to be an informative asset to explain the coexistence of two amyloid disorders.

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.

Self-assembly of artificial sweetener aspartame adversely affects phospholipid membranes: plausible reason for its deleterious effects.

The prolonged intake of the artificial sweetener aspartame is known to have deleterious effects. Our biophysical experimentations indicate that aspartame forms self-assembled cytotoxic fibrillar etiologies that affect the intrinsic integrity of the phospholipid membrane bilayer through electrostatic interaction and hydrophobic insertion, thereby making the membrane less rigid and more heterogeneous.