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The nature of linear photophysical and nonlinear optical properties of a new squaraine derivative 2,4-bis[4-(azetidyl)-2-hydroxyphenyl]squaraine (

Chemoresistance is one of the major challenges for cancer treatment, more recently ascribed to defective mitochondrial outer membrane permeabilization (MOMP), significantly diminishing chemotherapeutic agent-induced apoptosis. A boron-dipyrromethene (BODIPY) chromophore-based triarylsulfonium photoacid generator (BD-PAG) was used to target mitochondria with the aim to regulate mitochondrial pH and further depolarize the mitochondrial membrane. Cell viability assays demonstrated the relative biocompatibility of BD-PAG in the dark while live cell imaging suggested high accumulation in mitochondria. Specific assays indicated that BD-PAG is capable of regulating mitochondrial pH with significant effects on mitochondrial membrane depolarization. Therapeutic tests using chlorambucil in combination with BD-PAG revealed a new strategy in chemoresistance suppression.

Acid-sensing ion channels (ASICs), present in both central and peripheral neurons, respond to changes in extracellular protons. They play important roles in many symptoms and diseases, such as pain, ischemic stroke and neurodegenerative diseases. Herein, we report a novel approach to activate ASICs with the precision of light using organic photoacid generators (PAGs), which are molecules that release H(+) upon light illumination, and have been recently used in biomedical studies. The PAGs showed low toxicity in dark conditions. Under LED light illumination, ASICs activation and consequent calcium ion influx was monitored and analysed by fluorescence microscopy, and showed a strong light-dependent response. This approach allows the activation of ASICs with the precision of light, and may be valuable to help better elucidate the molecular mechanism of ASICs and unveil their roles in physiology, pathophysiology, and behaviour.

The development of contrast agents based on fluorescent nanoparticles with high brightness and stability is a key factor to improve the resolution and signal-to-noise ratio of current fluorescence imaging techniques. However, the design of bright fluorescent nanoparticles remains challenging due to fluorescence self-quenching at high concentrations. Developing bright nanoparticles showing FRET emission adds several advantages to the system, including an amplified Stokes shift, the possibility of ratiometric measurements, and of verifying the nanoparticle stability. Herein, we have developed Förster resonance energy transfer (FRET)-based nanovesicles at different dye loadings and investigated them through complementary experimental techniques, including conventional fluorescence spectroscopy and super-resolution microscopy supported by molecular dynamics calculations. We show that the optical properties can be modulated by dye loading at the nanoscopic level due to the dye's molecular diffusion in fluid-like membranes. This work shows the first proof of a FRET pair dye's dynamism in liquid-like membranes, resulting in optimized nanoprobes that are 120-fold brighter than QDot 605 and exhibit >80% FRET efficiency with vesicle-to-vesicle variations that are mostly below 10%., J.M.-F. gratefully thanks the financial support received by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 712949 (TECNIOspring PLUS) and from the Agency for Business Competitiveness of the Government of Catalonia. We acknowledge the European Commission (EC) FP7-PEOPLE-2013-Initial Training Networks (ITN) “NANO2FUN” project no. 607721 for being the spark that initiates this work and EC project MSCA-RISE-2020 "MICRO4NANO" project no.101007804. This work was also financially supported by Generalitat de Catalunya (grant no. 2017-SGR-918), the Ministry of Economy, Industry, and Competitiveness (Spain), through the “MOTHER” project (MAT2016-80826-R), the Ministry of Science and Innovation of Spain through the grant PID2019-105622RB-I00 (Mol4Bio). ICMAB-CSIC also acknowledges support from the MINECO through the Severo Ochoa Programme FUNFUTURE (SEV-2015-0496 and CEX2019-000917-S). K.D.B. acknowledges the National Science Foundation (CBET-1517273 and CHE-1726345). C.S. and A.P. benefited from the equipment and framework of the COMP-HUB Initiative, funded by the “Departments of Excellence” program of the Italian Ministry for Education, University and Research (MIUR, 2018-2022). We thank the CESGA Supercomputing Center for technical support and the use of computational resources. The contribution of S.I.-T. has been done under the Materials Science PhD program in the Barcelona Autonomous University (UAB). Characterizations of nanovesicles were made at the ICTS “NANBIOSIS”, more specifically by the U6 unit of CIBER-BBN. The authors would like also to thank the collaboration of Hamamatsu Photonics for the quantum yield determinations using the Quantaurus-QY Plus UV–NIR absolute PL quantum yield spectrometer., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

Hemorrhage is often a major component of traumatic brain injury (TBI). Red blood cells (RBCs) accumulated at the hemorrhagic site undergo hemolysis upon energy depletion. Hemolysis of RBCs is expected to release free iron into the central nervous system (CNS) that must be managed to prevent iron neurotoxicity. Here, we examine the hypothesis that chronic alcohol consumption, as a secondary stressor, may increase iron toxicity in an animal model of TBI by altering the iron management pathways. To our best knowledge, this innovative idea with significant scientific premises has not been examined to date. We found huge accumulation of free irons at the site of hemorrhage with evidence of hemolytic activity. Our observation showed that alcohol use altered the three distinct iron management pathways of transferrin/hemosiderin binding, lipocalin 2/heme oxygenase 1/ferritin system, and microglial phagocytosis. Presence of alcohol prolonged the expression of lipocalin 2 at the site of hemorrhage compared with injury alone, while the combined effects of alcohol and TBI elevated the levels of heme oxygenase 1 earlier than TBI alone. Hippocampus, neocortex, and around vessels near the site of impact appeared to be the prominent brain regions of induction. The presence of alcohol notably increased the levels of ferritin that sustained for up to 7 days. We also provide evidence that microglia also play a role in iron management through RBC phagocytosis. These results reveal the intricacy and plasticity of iron management and highlight the importance of proper iron regulation in the CNS.

Capitalizing on the nucleophilic addition of hydrazine toward the central cyclobutenyl core and affinity of aldehydes to hydrazine group, two water-soluble squaraine dyes (SQOH and SQPY) were synthesized as sensitive colorimetric and fluorescent chemosensors for aldehydes. The color change from blue to colorless and back to blue these sensors underwent was readily observed, even by the naked eyes. The response was fast (less than 1 s) and the detection limit for formaldehyde as an example was about 60 μM. In contrast to the previous nucleophilic attack to squaraines and the other amine references studied, this work underwent a whole ON-OFF-ON sensing circle based on the characteristics of hydrazine. Meanwhile, the different photophysical properties of the two squaraines related to their different structures were also demonstrated. Importantly, a possible sensing mechanism is proposed suggesting these types of dyes hold great potential in the area of rapid, sensitive, and convenient detection of aldehydes.

A novel series of silyl-yne containing chalcone derivatives 5a-5j was synthesized by exploiting Sonogashira coupling reaction and Claisen-Schimdt condensation reaction. The synthesized derivative were characterized by spectroscopic and elemental analysis. The selective inhibition of carbonic anhydrases is considered critical in the field of medicinal chemistry because carbonic anhydrases exits in several isoforms. Synthesized compounds were subjected to carbonic anhydrase –II assay. Except 5j, the other derivatives exhibited better potential than standard acetazolamide. Compound 5e was found to be potent derivative in the series with IC50 value 0.054 ± 0.001 µM. Binding analysis revealed that most potent derivative 5e binds in the active site of CA-II and single π-π stacking interaction was observed between ring structure of ligand and Phe129 having bond length 4.90 A. Pharmacokinetics elicited that compounds obey Lipinski’s rule and show significant drug score.

A small set of four new fluorenyl chromophores (5-5a-c) was accomplished by stepwise nucleophilic substitution, Friedel-Crafts acylation, Ullman coupling, aldol condensation and cyclization reactions. The fluorene moiety was substituted at 2,7,9 and 9′ positions with diverse groups. The synthesized derivatives were characterized by FTIR, 1H-NMR and 13C-NMR spectroscopic techniques. The optical properties were evaluated by by UV-VIS absorption and Fluorescence studies. HOMO and LUMO energy levels were evaluated by electrochemical studies and were found at −5.37-5.83 eV and − 2.47-2.94 eV respectively with band gap energy values 2.88 to 2.91 eV. The band gap energy values suggested that these synthesized molecules can be manipulated in the designing of blue and green OLEDS.

Fluorescent organic nanoparticles (FONs) are emerging as an attractive alternative to the well-established fluorescent inorganic nanoparticles or small organic dyes. Their proper design allows one to obtain biocompatible probes with superior brightness and high photostability, although usually affected by low colloidal stability. Herein, we present a type of FONs with outstanding photophysical and physicochemical properties in-line with the stringent requirements for biomedical applications. These FONs are based on quatsome (QS) nanovesicles containing a pair of fluorescent carbocyanine molecules that give rise to Förster resonance energy transfer (FRET). Structural homogeneity, high brightness, photostability, and high FRET efficiency make these FONs a promising class of optical bioprobes. Loaded QSs have been used for in vitro bioimaging, demonstrating the nanovesicle membrane integrity after cell internalization, and the possibility to monitor the intracellular vesicle fate. Taken together, the proposed QSs loaded with a FRET pair constitute a promising platform for bioimaging and theranostics., J.M.F. gratefully thank the financial support received by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 712949 (TECNIOspring PLUS) and from the Agency for Business Competitiveness of the Government of Catalonia (TECSPR17-1-0035). This work was also financially supported by the Ministry of Economy, Industry, and Competitiveness, Spain, through the “MOTHER” project (MAT2016-80826-R) and the “FLOWERS” project (FUNMAT-FIP-2016) funded by the Severo Ochoa (SEV-2015-0496) awarded to ICMAB. Instituto de Salud Carlos III, through “Acciones CIBER”, also supported this work. Characterization of nanovesicles was made at the ICTS “NANBIOSIS”, more specifically by the U6 unit of CIBER-BBN. The authors acknowledge the European Commission (EC) FP7-PEOPLE-2013-Initial Training Networks (ITN) “NANO2FUN” project no. 607721 for being the spark that initiated this work. K.B.D. acknowledges support from the National Science Foundation (CBET-1517273 and CHE-1726345). C.S. and A.P. benefited from the equipment and framework of the COMP-HUB Initiative, funded by the “Departments of Excellence” program of the Italian Ministry for Education, University and Research (MIUR, 2018-2022).

A comprehensive experimental and theoretical study of linear photophysical properties, such as excited-state relaxation, two-photon absorption, and stimulated emission spectra of the symmetrical fluorene derivative 2,2′-((1E,1′E)-(9,9-diethyl-9H-fluorene-2,7-diyl)bis(ethene-2,1-diyl))bis(1-methyl-1H-pyrrole) (1), is presented. The steady-state absorption, fluorescence, excitation, and excitation anisotropy spectra of 1 in organic solvents of different polarities are investigated experimentally and modeled. The fluorescence solvatochromism of 1 suggests the occurrence of symmetry breaking in the first excited state. The nature of fast relaxation processes in the excited state of 1, with the characteristic times of several picoseconds, is investigated by transient absorption femtosecond pump–probe spectroscopy. The spectral properties of 1 are satisfactorily described by an essential-state model that, accounting for electron–vibration coupling and for polar solvation, addresses spectroscopic features not on...

With the objective of developing new near-infrared fluorescent probes and understanding the effect molecular structure exerts on physical properties, a series of aniline-based squaraine dyes with different number and position of methoxy substituents adjacent to the squaraine core were synthesized and investigated. Using both computational and experimental methods, we found that the subtle changes of the number or position of the methoxy substituents influenced the twisting angle of the structure and led to significant variations in optical properties. Moreover, the methoxy substituent also affected aggregation behavior due to steric effects. The X-ray crystal structure of one of the key members of the series, SD-2a, clearly demonstrates the distortion between the four-membered squaraine core and the adjacent aniline ring due to methoxy substitution. Structure-related fast relaxation processes were investigated by femtosecond pump–probe experiments and transient absorption spectra. Quantum chemical calcula...

The requisition of small light emitting organic molecules is on the rise in the field of organic electronics. This study is aimed at synthesis of fluorene based chromophores which possess promising optoelectronic properties. The characterization of synthesized derivatives was carried out by spectroscopy ( 1 H-NMR and 13 C-NMR) and spectrometry (EI-MS). The optical properties evaluated by using UV-Vis spectroscopy, were from 394 to 420 nm, Fluorescence ranged 48 nm-113 nm, HOMO energy levels are −6.75 eV to −7.15 eV LUMO -4.08 to −4.52eV with a band gap energy values 2.63–2.67 eV. The band gap energy values suggest that these synthesized molecules can be manipulated in the designing of blue and green OLEDS.

A series of small organic molecules were synthesized by exploiting the bay and imide positions of the perylene nucleus. The synthesized compounds 1–11 were characterized by spectroscopic and elemental analyses. These molecules show yellowish color in solution and are highly soluble in dichloromethane. Compound 7 shows a bandgap of 1.7 eV and a Stokes shift of 27. From these results, we infer that this compound can serve as structural template in the design of organic electronics. Moreover, compound 7 shows higher Td (370°C) and Tg (132°C) values, which reflect its high thermal stability.

The electronic nature of 4-hydroxy-1H-pyrrolo[3,4-c]pyridine-1,3,6(2H,5H)-trione (HPPT) was comprehensively investigated in liquid media at room temperature using steady-state and time-resolved femtosecond transient absorption spectroscopic techniques. The analysis of the linear photophysical and photochemical parameters of HPPT, including steady-state absorption, fluorescence and excitation anisotropy spectra, along with the lifetimes of fluorescence emission and photodecomposition quantum yields, revealed the nature of its large Stokes shift, specific changes in the permanent dipole moments under electronic excitation, weak dipole transitions with partially anisotropic character, and high photostability. Transient absorption spectra of HPPT were obtained with femtosecond resolution and no characteristic solvate relaxation processes in protic (methanol) solvent were revealed. Efficient light amplification (gain) was observed in the fluorescence spectral range of HPPT, but no super-luminescence and lasing phenomena were detected. The electronic structure of HPPT was also analyzed with quantum-chemical calculations using a DFT/B3LYP method and good agreement with experimental data was shown. The development and investigation of new pyrrolo[3,4-c]pyridine derivatives are important due to their promising fluorescent properties and potential for use in physiological applications.

Delivery of hydrophobic materials in biological systems, for example, contrast agents or drugs, is an obdurate challenge, severely restricting the use of materials with otherwise advantageous properties. The synthesis and characterization of a highly stable and water-soluble nanovesicle, referred to as a quatsome (QS, vesicle prepared from cholesterol and amphiphilic quaternary amines), that allowed the nanostructuration of a nonwater soluble fluorene-based probe are reported. Photophysical properties of fluorenyl–quatsome nanovesicles were investigated via ultraviolet–visible absorption and fluorescence spectroscopy in various solvents. Colloidal stability and morphology of the nanostructured fluorescent probes were studied via cryogenic transmission electronic microscopy, revealing a “patchy” quatsome vascular morphology. As an example of the utility of these fluorescent nanoprobes, examination of cellular distribution was evaluated in HCT 116 (an epithelial colorectal carcinoma cell line) and COS-7 (an African green monkey kidney cell line) cell lines, demonstrating the selective localization of C-QS and M-QS vesicles in lysosomes with high Pearson’s colocalization coefficient, where C-QS and M-QS refer to quatsomes prepared with hexadecyltrimethylammonium bromide or tetradecyldimethylbenzylammonium chloride, respectively. Further experiments demonstrated their use in time-dependent lysosomal tracking., This work was supported by the DGI, Spain, “Grants BEWELL CTQ2013-40480-R” and “Mother MAT 2016-80826- R”, by AGAUR, Generalitat de Catalunya, “Grant 2014-SGR17”, the Networking Research Center on Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), and the Spanish Ministry of Economy and Competitiveness, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015-0496) through FIP Flowers project. Characterizations of nanovesicles were made at the ICTS “NANBIOSIS”, more specifically by the U6 unit of CIBERBBN. The research leading to these results received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7/ 2007−2013 under REA grant agreement no. 607721 (Nano2- Fun) A.A. is enrolled in the Materials Science Ph.D. program of UAB. K.D.B. and X.L. acknowledge support from the National Science Foundation (CBET-1517273).

A comprehensive study of the photophysical properties of triethylene glycol monomethyl ether (TEG)-substituted squaraine dye SQ1 is presented. SQ1 exhibits strong absorption and intense fluorescence emission in the far-red spectral region and high photostability. Interestingly, bis-tegylated SQ1 was characterized to exhibit properties different from its tetrahydroxy analog (SQ2), to which we ascribe attenuation of intermolecular interactions as a result of steric hindrance through introduction of two TEG chains adjacent to the squaraine core. The photophysical properties of SQ1 were also investigated as a function of temperature and pH. In cetyltrimethylammonium bromide (CTAB) micellar media (1.0 mm), the fluorescence quantum yield of SQ1 increased dramatically to 0.22, compared with 0.02 in water. Based on this discovery, SQ1 was found to display excellent sensitivity and selectivity to the presence of cyanide ions (CN–), with a limit of detection of 1.7 µm. The hypothesized CN– sensing mechanism was probed, and visual test strips were developed. This work broadens the family of squaraine dyes and demonstrates SQ1 for use as a fluorescent or visual sensing probe.

Two cationic conjugated polyelectrolytes (CPEs) based on poly(phenylene ethynylene) are found to exhibit efficient 2-photon excited fluorescence. In particular, the CPE aggregates display enhanced 2-photon absorption compared to the nonaggregated states. The CPEs are used as 2-photon absorption sensitizers to harvest light and amplify the fluorescence from green fluorescent protein (GFP) through Forster resonance energy transfer. Considerably enhanced GFP fluorescence under near-infrared 2-photon excitation is demonstrated both in solution and in HeLa cells. The results suggest applications in 2-photon fluorescence imaging of cells, tissues, and organs of living animals expressing GFP.

The steady-state and time-resolved linear spectral properties, two-photon absorption spectra and fast relaxation processes in the excited states of styryl base-type derivatives were investigated. The nature of linear absorption, fluorescence and excitation anisotropy spectra were analyzed in solvents of different polarity at room temperature and specific dependence of the solvatochromic behavior on the donor-acceptor strength of the terminal substituents was shown. Two-photon absorption (2PA) efficiency of styryl dye bases was determined in a broad spectral range using two-photon induced fluorescence technique, and cross-sections maxima of ~ 100 GM were found. The excited state absorption (ESA) and fast relaxation processes in the molecular structures were investigated by transient absorption femtosecond pump-probe methodology. The role of twisted intramolecular charge transfer (TICT) effect in the excited state of styryl dye base with dimethylamino substituent was shown. The experimental spectroscopic data were also verified by quantum chemical calculations at the Time Dependent Density Functional Theory level, combined with a polarizable continuum model.

Fluorescent contrast agents are important tools in cell biology and medical imaging due to their high sensitivity and relative availability. Diketopyrrolopyrrole (DPP) derivatives have been recently studied for applications in bioimaging, but certain drawbacks due to their inherent structure have stifled progress towards their widespread implementation. Aggregation caused quenching (ACQ) associated with π-π stacking in relatively rigid extended conjugation systems as well as hydrophobicity of previously reported DPPs make most unsuitable for biological imaging applications. Addressing these deficiencies, we report the synthesis and photophysical characterization of two new water-soluble diketopyrrolopyrole (DPP) probes that exhibit pronounced protein-induced fluorescence enhancement (PIFE) upon binding serum albumin protein. In vitro studies were also performed showing low cytotoxicity for the new DPP probes. Two-photon fluorescence microscopy (2PFM) images were obtained via excitation at 810 nm and emission in the NIR window of biological transparency, illustrating the potential of these compounds as nonlinear optical bioimaging probes.

A new halogenated 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivative was designed as a singlet-oxygen photosensitizer (PS) for use as a photodynamic therapy (PDT) agent, and its photophysical properties were characterized. The PS, having two iodine atom substituents, exhibited a low fluorescence quantum yield (ΦFL) of 0.02 and high singlet-oxygen-generation quantum yield (ΦΔ) of 0.93. Furthermore, in vitro photodynamic activities were evaluated to assess the potential of using the PS for PDT. A propidium iodide (PI) fluorescence assay and live-cell imaging of Lewis lung carcinoma (LLC) cells demonstrated that the cellular damage is induced by the photosensitization of the BODIPY dye, which subsequently leads to cell death by necrosis.q

A series of dyes 2–5 based on 5-thienyl-2,1,3-benzothiadiazole and 5-thienyl-2,1,3-benzoselenadiazole cores were synthesized as near-infrared-emitting two-photon-absorbing fluorophores. Fluorescence maxima wavelengths as long as 714 nm and quantum yields as high as 0.67 were realized. The fluorescence quantum yields of dyes 2–4 were nearly constant, regardless of solvent polarity. These diazoles exhibited large Stokes shifts (>110 nm) and high two-photon figure of merit. Cells incubated on a 3D scaffold with probe 4 (encapsulated in Pluronic micelles) exhibited bright fluorescence, enabling 3D two-photon fluorescence imaging to a depth of 100 μm.

Alaa A Fadhel,1 Xiling Yue,1 Ebrahim H Ghazvini Zadeh,1 Mykhailo V Bondar,2 Kevin D Belfield3 1Department of Chemistry, University of Central Florida, Orlando, FL, USA; 2Institute of Physics NASU, Kiev, Ukraine; 3Department of Chemistry and Environmental Science, College of Science and Liberal Arts, New Jersey Institute of Technology, University Heights, Newark, NJ, USA Abstract: Photodynamic therapy (PDT) processes involving the production of singlet oxygen face the issue of oxygen concentration dependency. Despite high oxygen delivery, a variety of properties related to metabolism and vascular morphology in cancer cells result in hypoxic environments, resulting in limited effectiveness of such therapies. An alternative oxygen-independent agent whose cell cytotoxicity can be remotely controlled by light may allow access to treatment of hypoxic tumors. Toward that end, we developed and tested both polyethylene glycol (PEG)-functionalized and hydrophilic silica nanoparticle (SiNP)-enriched photoacid generator (PAG) as a nontraditional PDT agent to effectively induce necrotic cell death in HCT-116 cells. Already known for applications in lithography and cationic polymerization, our developed oxygen-independent PDT, whether free or highly monodispersed on SiNPs, generates acid when a one-photon (1P) or two-photon (2P) excitation source is used, thus potentially permitting deep tissue treatment. Our study shows that when conjugated to SiNPs with protruding amine functionalities (SiNP–PAG9), such atypical PDT agents can be effectively delivered into HCT-116 cells and compartmentalize exclusively in lysosomes and endosomes. Loss of cell adhesion and cell swelling are detected when an excitation source is applied, suggesting that SiNP–PAG9, when excited via near-infrared 2P absorption (a subject of future investigation), can be used as a delivery system to selectively induce cell death in oxygen-deprived optically thick tissue. Keywords: oxygen-independent photodynamic therapy, photoacid generator, silica nanoparticles, stimuli-responsive, sulfonium salt

Mitochondria are essential targets for treatment of diseases with mitochondrial disorders such as diabetes, cancer, and cardiovascular and neurodegenerative diseases. Mitochondria penetrating peptides (MPPs) are composed of cationic and hydrophobic amino acids that can target and permeate the mitochondrial membrane. Herein, a novel d-argine-phenylalanine-d-argine-phenylalanine-d-argine-phenylalanine-NH2 (rFrFrF) was tagged with a rhodamine-based fluorescent chromophore (TAMRA). This probe (TAMRA-rFrFrF) exhibited advantageous properties for long-term mitochondria tracking as demonstrated by fluorescence microscopy. Cell viability assays and oxygen consumption rates indicate low cytotoxicity and high biocompatibility of the new contrast agent. Colocalization studies suggest that TAMRA-rFrFrF is a promising candidate for continuous mitochondrial tracking for up to 3 days.

The efficient clearance of the interstitial waste metabolites is essential for the normal maintenance of brain homeostasis. The brain lacks the lymphatic clearance system. Thus, the drainage of waste metabolites in the brain is dependent on a slow flow of cerebrospinal fluid (CSF) system. Glymphatic system claims the direct bulk flow transport of small size water-soluble waste metabolites into to the perivenous space by aquaporin-4 water channels of the astrocyte end-feet, but it did not address the diffusive clearance of large size waste metabolites. Here, we addressed the clearance mechanisms of large size waste metabolites from interstitial fluid to perivascular space as well as from CSF subarachnoid into perivascular space via the paravascular drainage. A low dose ethanol acting as a potent vasodilator promotes the dynamic clearance of waste metabolites through this perivascular-perivenous drainage path. We observed that ethanol-induced increased in vascular endothelial and smooth muscle cell reactivity regulated the enhanced clearance of metabolites. Here, activation of endothelial specific nitric oxide synthase (eNOS) by ethanol and generation of vasodilator nitric oxide mediates the interactive reactivity of endothelial-smooth muscle cells and subsequent diffusion of the CNS waste metabolites towards perivascular space. Detection of tracer dye (waste metabolite) in the perivenous space and in the blood samples further confirmed the improved clearance of waste metabolites through this unraveled interstitial-perivascular-perivenous clearance path. Our results suggest that alcohol intake at low-dose levels may promote clearance of neurological disease associated entangled proteins.

For bioimaging purposes, non-cytotoxic fluorescent labels, stable in biological media and capable of site-specific labeling are in upsurging demand. However, many fluorescent dyes with promising properties, such as fluorescent organic dyes, are poorly water-soluble and often lose their properties in water, limiting their use for bioapplications. The weak signals, poor photobleaching resistance, short fluorescence life time and low chemical stability are continuous challenges for the development of optimal fluorescent probes. The use of aqueous colloidal structures, such as nanovesicles, as nanocarriers for the loading of the organic dyes offers a promising strategy to overcome this limitation. As a matter of fact, we have engineered a new class of fluorescent organic nanoparticles (FONs) using thermodynamically stable nanovesicles named quatsomes (QS) [1-4]. QSs are new class of exceptionally stable small unilamellar vesicles with sizes smaller than 100nm, and formed by the self-assembly of sterols and quaternary ammonium surfactants. [5,6] Dye-loaded QSs can be prepared by a one-step method using compressed CO2, named depressurization of expanded liquid organic solution-suspension (DELOS-susp).[7] Indeed, it is a green technology leading to a formation of a highly homogenous dispersion of nanovesicles stables in an aqueous environment. The loading of water-insoluble carbocyanines dyes into QSs, has successfully proved the photostability of the obtained FONs in aqueous solutions, as well as, their valuable brightness [6]. They show excellent colloidal stability and structural homogeneity along with superior optical properties, in comparison with the fluorophores in solution. Dye-loaded QSs have enhanced optical properties, demonstrating the absence of non-fluorescent aggregates due to the Aggregation Caused Quenching (ACQ) effect, neither the formation of J- and H-aggregates was produced, in contrary to the well-known tendency of cyanines to aggregate [8]. Different methods for obtaining dye loaded nanoparticles were compared pointing the advantages of dye-loaded QS over other dye-based FONs, in terms of both, optical and colloidal properties. The effect of the dye loading on the physicochemical properties were studied as well as the brightness, showing higher brightness when dyes were located at the QS membrane. Moreover, experimental results were supported by molecular dynamics (MD) simulations which give information on the configuration of the dyes within the membrane. The potential of dye-loaded QSs for biological imaging was studied using a superresolution microscopy technique, the stochastic optical reconstruction microscopy (STORM). This study determine that dye-based QS are remarkable candidates as nanostructured probes for biological imaging, not only because of their photophysical properties but also, for their capabilities to be precisely decorated at their surfaces with targeting groups3 and to integrate small drugs or large biomolecules. All such benefits represent a certainly promising probe for bioimaging and, especially, for theragnostic nanomedicine. 1. Elizondo, E. et al. Influence of the Preparation Route on the Supramolecular Organization of Lipids in a Vesicular System. J. Am. Chem. Soc. 134, 1918–1921 (2012). 2. Ferrer-Tasies, L. et al. Quatsomes: Vesicles Formed by Self-Assembly of Sterols and Quaternary Ammonium Surfactants. Langmuir 29, 6519–6528 (2013). 3. Cabrera, I. et al. Multifunctional Nanovesicle-Bioactive Conjugates Prepared by a One-Step Scalable Method Using CO2-Expanded Solvents. Nano Lett. 13, 3766–3774 (2013). 4. Grimaldi, N. et al. Lipid-based nanovesicles for nanomedicine. Chem. Soc. Rev. 45, 6520–6545 (2016). 5. Silbaugh, D. A. et al. Highly Fluorescent Silicon Nanocrystals Stabilized in Water Using Quatsomes. Langmuir 33, 14366–14377 (2017). 6. Antonio, A. et al. Nanostructuring Lipophilic Dyes in Water Using Stable Vesicles, Quatsomes, as Scaffolds and Their Use as Probes for Bioimaging. Small 14, 1703851 (2018). 7. Ventosa, Nora; Veciana, Jaume; Sala, Santiago; Cano, M. Method for Obtaining Micro- and Nano-disperse systems. (2006). doi:WO/2006/079889 8. Gadde, S., Batchelor, E. K. & Kaifer, A. E. Controlling the Formation of Cyanine Dye H- and J-Aggregates with Cucurbituril Hosts in the Presence of Anionic Polyelectrolytes. Chem. – A Eur. J. 15, 6025–6031 (2009).

A novel mitochondria penetrating peptide (MPP) that can permeate the mitochondrial membrane for long-term tracking of mitochondria is reported. In-vitro studies indicate persistence of the MPP probe, low cytotoxicity, and high bio-compatibility.

The synthesis and comprehensive linear spectroscopic and nonlinear optical properties of a new BODIPY-based fluorene-containing derivative 4,4-difluoro-8-(4-{2-[2-(2-hydroxyethoxy)ethoxy]ethoxy}phenyl)-1,3,5,7-tetramethyl-2,6-di[(9,9-di{2-[2-(2-methoxyethoxy)ethoxy]ethyl}-9H-fluoren-2-yl)ethynyl]-4-bora-3a,4a-diaza-s-indacene (1) are reported. The steady-state absorption, emission, and excitation anisotropy spectra along with fluorescence lifetimes of 1 were analyzed in organic solvents of different polarity. The degenerate two-photon absorption (2PA) spectrum of 1 was obtained over a broad spectral range by the open aperture Z-scan method using 1 kHz femtosecond excitation, and the 2PA cross section had a maximum value of ∼400 GM. The one-photon stimulated emission depletion spectrum of 1 was determined by a fluorescence quenching method with values of stimulated emission cross sections close to the corresponding ones of the ground state linear absorption. The nature of ultrafast relaxation processes in ...

A highly water-soluble, fluorescence turn-on sensor for Ca(2+) is reported. The sensor affords high selectivity in sensing Ca(2+) over other biologically important metal cations. The dissociation constant of the sensor in binding Ca(2+) is 0.92 mm. Fluorescence microscopy experiments demonstrate that the sensor is cell-impermeable and capable of detecting extracellular Ca(2+) .

The synthesis, comprehensive linear photophysical and photochemical study, two-photon absorption (2PA) spectrum, ultrafast relaxation kinetics in the excited states, and efficient superluminescence properties of a new symmetrical three-armed star-shaped squaraine derivative (1) are presented. The steady-state spectral parameters of 1 in a number of organic solvents, including fluorescence excitation anisotropy spectra, revealed a weak interaction between the squaraine branches and the effect of symmetry breaking in the ground electronic state. The degenerate 2PA spectrum of 1 was obtained over a broad spectral range with a maximum cross section of ∼8000 GM using the open aperture Z-scan technique. The nature of the fast dynamic processes in the excited electronic states of 1 was investigated by the femtosecond transient absorption pump–probe method, revealing characteristic relaxation times of ∼3–4 ps. The efficient superluminescence emission of 1 was observed in relatively low concentration solution (≈ 2...

Two indole-based squaraine dyes, bearing two pyrenyl groups through vinyl or ethynyl linkers, were synthesized with the aim of enhancing the intramolecular charge transfer interaction in addition to improving their optical properties. The absorption and emission properties of these derivatives were determined to gain insight into the intensity of this type of interaction, their aggregation behavior, and for comparison with results obtained through quantum chemical calculations. Both compounds exhibited high photochemical stability, high molar absorptivity, large fluorescence quantum yields, and relatively low tendency of forming excimers in several solvents. Nonlinear spectroscopic studies revealed two-photon absorption (2PA) cross section maxima greater than 10 000 GM (1 GM = 1 × 10–50 cm4 s/photon), which are higher values relative to the indole-based squaraine core. Experimental results were compared with time-dependent DFT calculations. These observations contribute to the study of intramolecular char...

Unlike chemical synthesis, biological synthesis of nanoparticles is gaining tremendous interest, and plant extracts are preferred over other biological sources due to their ample availability and wide array of reducing metabolites. In this project, we investigated the reducing potential of aqueous extract of Artemisia absinthium L. for synthesizing silver nanoparticles (AgNPs). Optimal synthesis of AgNPs with desirable physical and biological properties was investigated using ultra violet-visible spectroscopy (UV-vis), dynamic light scattering (DLS), transmission electron microscopy (TEM) and energy-dispersive X-ray analysis (EDX). To determine their appropriate concentrations for AgNP synthesis, two-fold dilutions of silver nitrate (20 to 0.62 mM) and aqueous plant extract (100 to 0.79 mg ml(-1)) were reacted. The results showed that silver nitrate (2mM) and plant extract (10 mg ml(-1)) mixed in different ratios significantly affected size, stability and yield of AgNPs. Extract to AgNO3 ratio of 6:4v/v resulted in the highest conversion efficiency of AgNO3 to AgNPs, with the particles in average size range of less than 100 nm. Furthermore, the direct imaging of synthesized AgNPs by TEM revealed polydispersed particles in the size range of 5 to 20 nm. Similarly, nanoparticles with the characteristic peak of silver were observed with EDX. This study presents a comprehensive investigation of the differential behavior of plant extract and AgNO3 to synthesize biologically stable AgNPs.