Unusually Sensitive Solid State Emissive 1,8-naphthalimide for Detection of Acid Vapors in Turn-off Mode and Base Vapors in Turn-on Mode.

A 4-amino-1,8-naphthalimide containing tetramethylpiperidine in N-position was synthesized. The prepared 1,8-naphthalimide was found to possess bright yellow-green fluorescence in a solid state, which could be switched-off in the presence of acid vapors and then switched-on after exposure on base vapors. The observed fluorescence quenching or enhancement, respectively, was more than 10-fold. This behavior was quite opposite to that of the similar 4-oxy-1,8-naphthalimide, in which a well-pronounced PET process operates. In addition, the observed fluorescence quenching was accompanied with color change from yellow to red. Based on these results, the reported 4-amino-1,8-naphthalimide was successfully applied as a reversible solid-state emissive chemosensing material for rapid detection of acid-base vapors for multiple usage.

Self-Assembled Molecular Complexes of 1,10-Phenanthroline and 2-Aminobenzimidazoles: Synthesis, Structure Investigations, and Cytotoxic Properties.

Three new molecular complexes (phen)3(2-amino-Bz)2(H+)(BF4-)·3H2O 5, (phen)3(2-amino-5(6)-methyl-Bz)2(H+)(BF4-)·H2O 6, and (phen)(1-methyl-2-amino-Bz)(H+)(BF4-) 7, were prepared by self-assembly of 1,10-phenanthroline (phen) and various substituted 2-aminobenzimidazoles. Confirmation of their structures was established through spectroscopic methods and elemental analysis. The X-ray diffraction analysis revealed that the crystal structure of 7 is stabilized by the formation of hydrogen bonds and short contacts. In addition, the molecular geometry and electron structure of molecules 5 and 6 were theoretically evaluated using density functional theory (DFT) methods. According to the DFT B3LYP/6-311+G* calculations, the protonated benzimidazole (Bz) units act as NH hydrogen bond donors, binding two phenanthrolines and a BF4- ion. Non-protonated Bz unit form hydrogen bonds with the N-atoms of a third molecule phen. The molecular assembly is held together by π-π stacking between benzimidazole and phenanthroline rings, allowing for N-atoms to associate with water molecules. The complexes were tested in vitro for their tumor cell growth inhibitory effects on prostate (PC3), breast (MDA-MB-231 and MCF-7), and cervical (HeLa) cancer cell lines using MTT-dye reduction assay. The in vitro cytotoxicity analysis and spectrophotometric investigation in the presence of ct-DNA, showed that self-assembled molecules 5-7 are promising DNA-binding anticancer agents warranting further in-depth exploration.

A Tutorial Review on the Fluorescent Probes as a Molecular Logic Circuit-Digital Comparator.

The rapid progress in the field of fluorescent probes and fluorescent sensing material extended this research area toward more complex molecular logic gates capable of carrying out a variety of sensing functions simultaneously. These molecules are able to calculate a composite result in which the analysis is not performed by a man but by the molecular device itself. Since the first report by de Silva of AND molecular logic gate, all possible logic gates have been achieved at the molecular level, and currently, utilization of more complicated molecular logic circuits is a major task in this field. Comparison between two digits is the simplest logic operation, which could be realized with the simplest logic circuit. That is why the right understanding of the applied principles during the implementation of molecular digital comparators could play a critical role in obtaining logic circuits that are more complicated. Herein, all possible ways for the construction of comparators on the molecular level were discussed, and recent achievements connected with these devices were presented.

Fused Triazinobenzimidazoles Bearing Heterocyclic Moiety: Synthesis, Structure Investigations, and In Silico and In Vitro Biological Activity.

[1,3,5]Triazino[1,2-a]benzimidazole-2-amines bearing heterocyclic moiety in 4-position were synthesized. The compounds were characterized by elemental analysis, IR, 1H-NMR, 13C-NMR, and HRMS spectroscopy. The molecular geometry and electron structure of these molecules were theoretically studied using density functional theory (DFT) methods. The molecular structure of the synthesized fused triazinobenzimidazole was confirmed to correspond to the 3,4-dihydrotriazinobenzimidazole structure through the analysis of spectroscopic NMR data and DFT calculations. The antinematodic activity was evaluated in vitro on isolated encapsulated muscle larvae (ML) of Trichinella spiralis. The results showed that the tested triazinobenzimidazoles exhibit significantly higher efficiency than the conventional drug used to treat trichinosis, albendazole, at a concentration of 50 µg/mL. The compound 3c substituted with a thiophen-2-yl moiety exhibited the highest anthelmintic activity, with a larvicidal effect of 58.41% at a concentration of 50 µg/mL after 24 h of incubation. Following closely behind, the pyrrole analog 3f demonstrated 49.90% effectiveness at the same concentration. The preliminary structure-anti-T. spiralis activity relationship (SAR) of the analogues in the series was discussed. The cytotoxicity of the benzimidazole derivatives against two normal fibroblast cells (3T3 and CCL-1) and two cancer human cell lines (MCF-7 breast cancer cells and chronic myeloid leukemia cells AR-230) was evaluated using the MTT-dye reduction assay. The screening results indicated that the compounds showed no cytotoxicity against the tested cell lines. An in silico study of the physicochemical and pharmacokinetic characteristics of the novel synthesized fused triazinobenzimidazoles showed that they were characterized by a significant degree of drug-likeness and optimal properties for anthelmintic agents.

Novel Fluorescent Benzimidazole-Hydrazone-Loaded Micellar Carriers for Controlled Release: Impact on Cell Toxicity, Nuclear and Microtubule Alterations in Breast Cancer Cells.

Fluorescent micellar carriers with controlled release of a novel anticancer drug were developed to enable intracellular imaging and cancer treatment simultaneously. The nanosized fluorescent micellar systems were embedded with a novel anticancer drug via the self-assembling behavior of well-defined block copolymers based on amphiphilic poly(acrylic acid)-block-poly(n-butyl acrylate) (PAA-b-PnBA) copolymer obtained by Atom Transfer Radical Polymerization (ATRP) and hydrophobic anticancer benzimidazole-hydrazone drug (BzH). Through this method, well-defined nanosized fluorescent micelles were obtained consisting of a hydrophilic PAA shell and a hydrophobic PnBA core embedded with the BzH drug due to the hydrophobic interactions, thus reaching very high encapsulation efficiency. The size, morphology, and fluorescent properties of blank and drug-loaded micelles were investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM), and fluorescent spectroscopy, respectively. Additionally, after 72 h of incubation, drug-loaded micelles released 3.25 µM of BzH, which was spectrophotometrically determined. The BzH drug-loaded micelles were found to exhibit enhanced antiproliferative and cytotoxic effects on MDA-MB-231 cells, with long-lasting effects on microtubule organization, with apoptotic alterations and preferential localization in the perinuclear space of cancer cells. In contrast, the antitumor effect of BzH alone or incorporated in micelles on non-cancerous cells MCF-10A was relatively weak.

Design and Synthesis of a Novel ICT Bichromophoric pH Sensing System Based on 1,8-Naphthalimide Fluorophores as a Two-Input Logic Gate and Its Antibacterial Evaluation.

The synthesis, sensor activity, and logic behavior of a novel 4-iminoamido-1,8-naphthalimide bichromophoric system based on a "fluorophore-receptor" architecture with ICT chemosensing properties is reported. The synthesized compound showed good colorimetric and fluorescence signaling properties as a function of pH and proved itself as a promising probe for the rapid detection of pH in an aqueous solution and base vapors in a solid state. The novel dyad is able to work as a two-input logic gate with chemical inputs H+ (Input 1) and HO- (Input 2) executing INHIBIT logic gate. The synthesized bichromophoric system and the corresponding intermediates demonstrated good antibacterial activity toward Gram (+) and Gram (-) bacteria when compared with the Gentamycin standard.

Fluorescent Probes as a Tool in Diagnostic and Drug Delivery Systems.

Over the last few years, the development of fluorescent probes has received considerable attention. Fluorescence signaling allows noninvasive and harmless real-time imaging with great spectral resolution in living objects, which is extremely useful for modern biomedical applications. This review presents the basic photophysical principles and strategies for the rational design of fluorescent probes as visualization agents in medical diagnosis and drug delivery systems. Common photophysical phenomena, such as Intramolecular Charge Transfer (ICT), Twisted Intramolecular Charge Transfer (TICT), Photoinduced Electron Transfer (PET), Excited-State Intramolecular Proton Transfer (ESIPT), Fluorescent Resonance Energy Transfer (FRET), and Aggregation-Induced Emission (AIE), are described as platforms for fluorescence sensing and imaging in vivo and in vitro. The presented examples are focused on the visualization of pH, biologically important cations and anions, reactive oxygen species (ROS), viscosity, biomolecules, and enzymes that find application for diagnostic purposes. The general strategies regarding fluorescence probes as molecular logic devices and fluorescence-drug conjugates for theranostic and drug delivery systems are discussed. This work could be of help for researchers working in the field of fluorescence sensing compounds, molecular logic gates, and drug delivery.

Design, Photochemistry, Logic Gates Behavior and Antibacterial Evaluation of ICT Systems based on 1,8-naphthalimides.

Ace naphthene as a primary material was nitrated and further reacted by various processes such as oxidation, imidation and amination in order to obtain dyad 5. The dyad 5 fluoresces in solvents of different polarity and the emission is shifted bathochromically with increasing the solvent polarity due to ICT enhancement, The fluorescent enhancement is greatest in case of chloroform (ФF = 0.48) on excitation at 420 nm,The influences of the pH on dyad 5 were also investigated, The results can be considered as representing off-on-off states. Dyad 5 executes two input XNOR logic gates, towards H+ and HO- ions, "off-on-off" switching behavior between H+ and HO- ions was observed, The synthesized compounds were tested for antimicrobial activity of Gram-positive and Gram-negative bacteria, The compounds tested have a good antibacterial activity as compared with standard compound (Gentamycin).

A Novel Fluorescent Probe for Determination of pH and Viscosity Based on a Highly Water-Soluble 1,8-Naphthalimide Rotor.

A novel highly water-soluble 1,8-naphthalimide with pH and viscosity-sensing fluorescence was synthesized and investigated. The synthesized compound was designed as a molecular device in which a molecular rotor and molecular "off-on" switcher were integrated. In order to obtain a TICT driven molecular motion at C-4 position of the 1,8-naphthalimide fluorophore, a 4-methylpiperazinyl fragment was introduced. The molecular motion was confirmed after photophysical investigation in solvents with different viscosity; furthermore, the fluorescence-sensing properties of the examined compound were investigated in 100% aqueous medium and it was found that it could be used as an efficient fluorescent probe for pH. Due to the non-emissive deexcitation nature of the TICT fluorophore, the novel system showed low yellow-green emission, which represented "power-on"/"rotor-on" state. The protonation of the methylpiperazine amine destabilized the TICT process, which was accompanied by fluorescence enhancement indicating a "power-on"/"rotor-off" state of the system. The results obtained clearly illustrated the great potential of the synthesized compound to serve as pH- and viscosity-sensing material in aqueous solution.

A Highly Water-Soluble and Solid State Emissive 1,8-Naphthalimide as a Fluorescent PET Probe for Determination of pHs, Acid/Base Vapors, and Water Content in Organic Solvents.

A new highly water-soluble 1,8-naphthalimide fluorophore designed on the "fluorophore-spacer-receptor1-receptor2" model has been synthesized. Due to the unusually high solubility in water, the novel compound proved to be a selective PET-based probe for the determination of pHs in aqueous solutions and rapid detection of water content in organic solvents. Based on the pH dependence of the probe and its high water solubility, the INH logic gate was achieved using NaOH and water as chemical inputs, where NaOH is the disabler and the water is an enabler. In addition, the probe showed effective fluorescence "off-on" reversibility on glass support after exposure to acid and base vapors, which defines it as a promising platform for rapid detection of acid/base vapors in the solid-state, thus extending the molecular sensing concept from solution to the solid support.

Low Molecular Weight Probe for Selective Sensing of PH and Cu2+ Working as Three INHIBIT Based Digital Comparator.

A novel simple molecular chemosensor 2 was synthesized and examined for pH, cations and anions detection. At pH values higher than 10, probe 2 switches on a green emission where the excited state intramolecular proton transfer (ESIPT) is ceased. Also, the probe absorption spectrum shows a clear pH dependence, and the probe aqueous solution (ethanol/water = 1:2, borate buffer) responds selectively and sensitively through its fluorescence spectrum to the presence of Cu2+. Job's plot gave a 2:1 stoichiometry of Probe-2/Cu2+ complex, which responds to the presence of S2- and H2PO4- in aqueous solution (ethanol/water = 1:2, borate buffer) by its absorption and fluorescence spectra. In addition, probe 2 mimics a digital comparator based on three INHIBIT logic gates by different outputs using HO- and H+ as inputs. Moreover, probe 2 also executes AND and NOT TRANSFER logic gates using Cu2+ and S2- as inputs.

L3 rootlet recurrent melanocytic schwannoma - case report and literature review.

First described by Miller in 1932, melanocytic schwannoma (MS) (melanotic schwannoma, pigmented schwannoma) is a rare variation of peripheral nerve sheet tumours with ectodermal origin occurring predominantly in somatic, but also in the autonomic peripheral system with around two hundred cases in the literature. Predominantly benign tumours, MS are still imaging and pathological challenge and can be easily misdiagnosed with more aggressive peripheral nerve tumours.We report a case of melanocytic schwannoma on L3 sensory rootlet with systematic literature review of nearly 200 cases presented in intracranial, paraspinal region, thoracic, abdominal or pelvic cavities and skin. Two-thirds of cases are part of Carney complex.We present a case of a 61-year-old male with a 3-month history of low back pain, progressive numbness and stiffness in the right thigh, shin and knee, tibial and peroneal paresis causing gait disturbance and neurological claudication. MRI findings present "sand clock" type intradural extramedullary tumour formation with extension to the L3 rootlet through right L3-L4 foramen, hypointense on T2 and hyperintense on T1. Pathological diagnosis of sporadic type melanocytic schwannoma was made via immunohistological and ultrastructural analysis. Thirteen months after total resection there was clinical and MRI evidence of recurrence of the tumour. Total resection and radiosurgery was performed with a recurrence free period of 14 months.A gold standard for melanocytic schwannoma treatment is gross total surgical resection. Despite being considered benign tumours, MS have a local or metastatic recurrence of around 13%. MRI imaging in most of the cases is insufficient and only exhaustive pathological and immunohistological examination is the key to diagnosis. Need of postoperative radiation therapy is still controversial. For the first time, a criterion for postoperative adjuvant therapy was established.

A chemosensoring molecular lab for various analytes and its ability to execute a molecular logical digital comparator.

We reported here the unique ability of a Rhodamine 6G-based probe (3) to detect discriminately several targets, including H+, HO-, Cu2+, Hg2+, Fe3+, Co2+, Cd2+, Zn2+, Sn2+, Ni2+, Al3+, Pb2+, Ce3+and Ag+, by unambiguously colorimetric and fluorimetric outcomes. In aqueous solutions, the presence of proton induced the ring-opening of rhodamine moiety but the presence of hydroxide induced the conversion of 2-hydroxyphenyl hydrazone moiety from the non-fluorescent benzenoid form into the fluorescent quinoid form. The probe could to distinguish between different cations in DMF and to work like an artificial tongue at molecular level. Several logic gates including OR, INHIBIT and TRANSFER, were performed by the probe. Moreover, the probe is able to execute three INHIBIT logic gates by two inputs, which was exploited to execute a digital molecular comparator.

Skin reactions among Bulgarian dental students: A self-report questionnaire survey.

BACKGROUND: Dental students are at high risk of developing adverse skin reactions following practical work during the dentistry degree program. They encounter multiple irritants and allergens that may cause skin reactions on exposed parts of the body, notably the hands. OBJECTIVES: To estimate the prevalence of skin reactions related to the pre-clinical and clinical training courses of the dentistry program and associated risk factors in Bulgarian dental students. METHOD: A cross-sectional study was performed using a self-report questionnaire. RESULTS: A total of 467 dental students completed the questionnaire (response 51.8%). The prevalence of self-reported skin symptoms was 21.2%. According to logistic regression analysis, the most important risk factors for work-related skin symptoms were a personal history of atopic dermatitis (odds ratio [OR] 3.92, 95% confidence interval [CI]: 1.99-7.72), allergic rhinoconjunctivitis and/or asthma (OR 1.94, 95%CI: 1.03-3.68), personal history of contact allergy (OR 2.19, 95%CI: 1.06-4.55), and hand washing >16 times a day (OR 2.42, 95%CI: 1.06-5.52). CONCLUSIONS: The results of this study suggest that work-related skin symptoms are frequent among dental students and indicate the need to establish effective primary preventive programs for occupational skin disorders at a national level.

A smart chemosensor: Discriminative multidetection and various logic operations in aqueous solution at biological pH.

A novel rhodamine-pyrazole based molecular probe was designed and easily synthesized. The probe could to detect several analytes in aqueous solution at biological pH (HEPES, pH = 7.2). Several heavy metal cations, including Cu2+, Fe3+, Al3+, Hg2+ and Ni2+ were detected discriminately by the probe. Also, the novel compound exhibited a good sensory selectivity towards S2O52- by both absorption and emission spectra. Moreover, probe/Cu2+ complex could to detect several anions, including F-, CN-, S2-, CH3COO-, CO32- and NO2-. Furthermore, the probe exhibited a high potential to work as a molecular system able to perform a number of logical operations such as AND, NAND, NOR and INHIBIT logic gates.

Synthesis of a single 1,8-naphthalimide fluorophore as a molecular logic lab for simultaneously detecting of Fe3+, Hg2+ and Cu2.

A novel fluorescence sensing 1,8-naphthalimide fluorophore is synthesized and investigated. The novel probe comprising two different binding moieties is capable to detect selectively Fe3+ over the other representative metal ions as well as a combination of biologically important cations such as Fe3+, Cu2+ and Hg2+ in the physiological range without an interfering effect of the pHs. Due to the remarkable fluorescence changes in the presence of Fe3+, Hg2+ and Cu2+ ions, INH and AND logic gates are executed and the system is able to act as a single output combinatorial logic circuit with three chemical inputs.

Synthesis, fluorescence-sensing and molecular logic of two water-soluble 1,8-naphthalimides.

Two novel highly water-soluble fluorescence sensing 1,8-naphthalimides are synthesized and investigated. The novel compounds are designed on the "fluorophore-receptor1-spacer-receptor2" model as a molecular fluorescence probe for determination of cations and anions in 100% aqueous media. The novel probes comprising N-imide and N-phenylpiperazine or morpholine substituents are capable to operate simultaneously via ICT and PET signaling mechanism as a function of pH and to recognize selectively Cu2+ and Hg2+ over the other representative metal ions. Due to the remarkable fluorescence changes in the presence of protons, hydroxyl anions, Hg2+ and Cu2+, INH and doubly disabled INH logic gates are executed and the systems are able to act as a single output combinatorial logic circuit with four chemical inputs.

Novel PAMAM Dendron as a Bichromophoric Probe Based on Rhodamine 6G and 1,8-Naphthalimide.

A novel PAMAM dendron designed as a wavelength-shifting bichromophore with 1,8-naphthalimide energy "donor" capable of absorbing light and efficiently transferring the energy to a focal Rhodamine 6G "acceptor" was synthesized and investigated. Moreover, the system was configured on the "fluorophore-spacer-receptor" format. Thus, the distinguishing features of FRET systems were successfully combined with the properties of photoinduced electron transfer and classical ring-opening sensor systems. The synthesized compound shows excellent signaling properties towards protons, Hg(2+) and Fe(3+) ions, therefore, the system is able to act as an one-output combinatorial logic circuit with four chemical inputs.

Novel nanosized water soluble fluorescent micelles with embedded perylene diimide fluorophores for potential biomedical applications: cell permeability, localization and cytotoxicity.

Novel biocompatible water-soluble fluorescent micelles with embedded perylene diimides (PDI) for intracellular applications have been prepared by self assembling of amphiphilic poly(vinyl alcohol)-b-poly(acrylonitrile) (PVA-b-PAN) copolymers in the presence of synthesized fluorophores. Amphiphilic PVA-b-PAN copolymers were obtained by selective hydrolysis of well-defined poly(vinyl acetate)-b-poly(acrylonitrile) (PVAc-b-PAN) copolymer. The preparation of the novel fluorescence micelles consisting of PVA hydrophilic shell and PAN hydrophobic core with incorporated PDI fluorophores has been confirmed by DLS and TEM analysis. The cytotoxicity of the water-soluble fluorophores and their internalization into living cells depending on the micellar concentration have been tested. It was shown that they could successfully enter in living cells without destroying their morphology. The results obtained indicate that the novel water-soluble fluorescent micelles with embedded PDI fluorophores would be suitable for potential intracellular biomedical applications.

A highly selective ratiometric fluorescent pH probe based on a PAMAM wavelength-shifting bichromophoric system.

A novel PAMAM wavelength-shifting bichromophoric system has been successfully developed. Novel compound was configured as a light harvesting antenna where the system surface is labeled with yellow-green emitting 4-(N,N-dimethylamino)ethylamino-1,8-naphthalimide "donor" units capable of absorbing light and efficiently transferring the energy to a focal Rhodamine 6G "acceptor". The periphery of the system was designed on the "fluorophore-spacer-receptor" format, capable of acting as a molecular fluorescence photoinduced electron transfer based probe. Due to the both effects, photoinduced electron transfer in the periphery of the system and pH dependent rhodamine core absorption, novel antenna is able to act as a selective ratiometric pH fluorescence probe in aqueous medium. Thus, the distinguishing features of the fluorescence resonance energy transfer systems were successfully combined with the properties of classical ring-opening charge transfer systems, which may be beneficially for monitoring pH variations in complex samples.