Transcriptome Dynamics Underlying Planticine®-Induced Defense Responses of Tomato (Solanum lycopersicum L.) to Biotic Stresses.

The induction of natural defense mechanisms in plants is considered to be one of the most important strategies used in integrated pest management (IPM). Plant immune inducers could reduce the use of chemicals for plant protection and their harmful impacts on the environment. Planticine® is a natural plant defense biostimulant based on oligomers of α(1→4)-linked D-galacturonic acids, which are biodegradable and nontoxic. The aim of this study was to define the molecular basis of Planticine's biological activity and the efficacy of its use as a natural plant resistance inducer in greenhouse conditions. Three independent experiments with foliar application of Planticine® were carried out. The first experiment in a climatic chamber (control environment, no pest pressure) subjected the leaves to RNA-seq analysis, and the second and third experiments in greenhouse conditions focused on efficacy after a pest infestation. The result was the RNA sequencing of six transcriptome libraries of tomatoes treated with Planticine® and untreated plants; a total of 3089 genes were found to be differentially expressed genes (DEGs); among them, 1760 and 1329 were up-regulated and down-regulated, respectively. DEG analysis indicated its involvement in such metabolic pathways and processes as plant-pathogen interaction, plant hormone signal transduction, MAPK signaling pathway, photosynthesis, and regulation of transcription. We detected up-regulated gene-encoded elicitor and effector recognition receptors (ELRR and ERR), mitogen-activated protein kinase (MAPKs) genes, and transcription factors (TFs), i.e., WRKY, ERF, MYB, NAC, bZIP, pathogenesis-related proteins (PRPs), and resistance-related metabolite (RRMs) genes. In the greenhouse trials, foliar application of Planticine® proved to be effective in reducing the infestation of tomato leaves by the biotrophic pathogen powdery mildew and in reducing feeding by thrips, which are insect herbivores. Prophylactic and intervention use of Planticine® at low infestation levels allows the activation of plant defense mechanisms.

Surprising Solid-State ESIPT Emission from Apparently Ordinary Salicyliden Glycinates Schiff Bases.

Excited-State Intramolecular Photon Transfer (ESIPT) is known for the geometry-related phenolic and imine groups. The Schiff bases formed upon condensation of salicyl aldehyde and glycine led to the formation of ESIPT models. A series of alkali metal salicyliden glycinates were analyzed by X-ray diffraction of their monocrystals and spectroscopy measurements. The X-ray analysis revealed varied hydration levels between the salts. They adapted trans geometry on the imine groups and mostly anticlinal conformation with the neighboring atoms, which is different from the other structurally-related compounds in literature. Fluorescence of these compounds was found for the crystalline forms only. Protonation of the imine nitrogen atom and further proton distribution was consistent with the ESIPT theory, which also explained the observed fluorescence with the highest Stokes shift of 10,181 cm-1 and 10.1% of fluorescence quantum yield for the sodium salt.

Hybrid, dual visible and near-infrared fluorescence emission of (6,5) single-walled carbon nanotubes modified with fluorescein through aryl diazonium salt chemistry.

The aryl diazonium salt chemistry offers enhancement of near-infrared (NIR) emission of single-walled carbon nanotubes (SWCNTs), although, the attachment of functional molecules which could bring hybrid properties through the process is underdeveloped. In this work, we utilize aryl diazonium salt of fluorescein to createsp3defects on (6,5) SWCNTs. We study the influence of pH on the grafting process identifying that pH 5-6 is necessary for a successful reaction. The fluorescein-modified (6,5) SWCNTs (F-(6,5) SWCNTs) exhibit red-shiftedE11* emission in the NIR region attributed to luminescentsp3defects, but also visible (Vis) fluorescence at 515 nm from surface-attached fluorescein molecules. The fluorescence in both Vis and NIR regions of F-(6,5) SWCNTs exhibit strong pH-dependency associated with the dissociation of fluorescein molecules with an indication of photoinduced-electron transfer quenching the Vis emission of fluorescein dianion. The F-(6,5) SWCNTs could potentially be used for dual-channel medical imaging as indicated by our preliminary experiments. We hope that our research will encourage new, bold modifications of SWCNTs with functional molecules introducing new, unique hybrid properties.

A step towards gadolinium-free bioresponsive MRI contrast agent.

The last 30 years of gadolinium-based "static" MRI contrast agents motivated to investigate bioresponsive agents with endogenous paramagnets. Iron(III) chelated by N,O-aminophenol skeleton of high versatility, and tuning potential was studied. The two-step convenient route of the ligand is characterized by high selectivity and allows for building a tunable chelate system. Functionalization with galactose endows a bioresponsive character sensitive to the enzyme activity. Direct relaxometric measurements of the resulting complexes revealed extremely high relaxivity of 5.62 mmol/dm3·s-1 comparable to classic gadolinium complexes. Enzymatic hydrolysis leads to relaxivity change by over 80%. Phantom MRI studies prove the bioresponsive character by contras percentage change within the range 40-275%. Cytotoxicity studies showed 70-90% viability of HeLa cells of the iron complexes. Proposed iron-based chelates with galactosidase-sensitive fragment express unequivocal relaxivity and MRI contras change and good biocompatibility. Therefore, these complexes are a promising step towards modern, bioresponsive MRI contrast agents with a "human-friendly" metal.

Targeted PET/MRI Imaging Super Probes: A Critical Review of Opportunities and Challenges.

Recently, the demand for hybrid PET/MRI imaging techniques has increased significantly, which has sparked the investigation into new ways to simultaneously track multiple molecular targets and improve the localization and expression of biochemical markers. Multimodal imaging probes have recently emerged as powerful tools for improving the detection sensitivity and accuracy-both important factors in disease diagnosis and treatment; however, only a limited number of bimodal probes have been investigated in preclinical models. Herein, we briefly describe the strengths and limitations of PET and MRI modalities and highlight the need for the development of multimodal molecularly-targeted agents. We have tried to thoroughly summarize data on bimodal probes available on PubMed. Emphasis was placed on their design, safety profiles, pharmacokinetics, and clearance properties. The challenges in PET/MR probe development using a number of illustrative examples are also discussed, along with future research directions for these novel conjugates.

Oxygen Functional Groups on MWCNT Surface as Critical Factor Boosting T2 Relaxation Rate of Water Protons: Towards Improved CNT-Based Contrast Agents.

PURPOSE: Salicyl (Sal) - among other oxygen functionalities - multi-walled carbon nanotubes (MWCNTs) and their nanohybrids are investigated as promising contrast agents (CA) in magnetic resonance imaging (MRI) or drug delivery platforms, due to their unique properties. The preliminary results and the literature reports were the motivation to endow high r2 relaxivities, excellent dispersibility in water, and biocompatibility to superparamagnetic MWCNTs nanohybrids. It was hypothesized that these goals could be achieved by, not described in the literature yet, two-stage oxygen functionalization of MWCNTs. RESULTS: Two structurally different MWCNT materials differing in diameters (44 and 12 nm) and the iron content (4.7% and 0.5%) are studied toward the functionalization effect on the T2 relaxometric properties. MWCNT oxidation is typically the first step of functionalization resulting in "first generation" oxygen functional groups (OFGs) on the surface. Until now, the impact of OFGs on the relaxivity of MWCNT was not truly recognized, but this study sheds light on this issue. By follow-up functionalization of oxidized MWCNT with 4-azidosalicylic acid through [2+1] cycloaddition of the corresponding nitrene, "second generation" of oxygen functional groups is grafted onto the nanohybrid, ie, Sal functionality. CONCLUSION: The introduced OFGs are responsible for an almost 30% increase in the relaxivity, which leads to remarkable r2 relaxivity of 951 mM-1s-1 (419 (mg/mL)-1s-1), the unprecedented value reported to date for this class of CAs. Also, the resulting nanohybrids express low cytotoxicity and superb diffusion after subcutaneous injection to a mouse.

Unprecedented Water Effect as a Key Element in Salicyl-Glycine Schiff Base Synthesis.

Salens, as chelating, double Schiff base ligands, are an important group utilized in transition metal catalysis. They have been used to build interesting functional metal-organic frameworks (MOFs). However, salens interacting with amino acids have also found applications in receptors. Here, we intended to form a "green" glycine-derived salen fragment, but the available literature data were contradictory. Therefore, we optimized the synthetic conditions and obtained the desired product as two different crystallographic polymorphs (orthorhombic Pcca and monoclinic P21/c space groups). Their structures differ in conformation at the glycine moiety, and the monoclinic form contains additional, disordered water molecules. Despite the high stability of Schiff bases, these newly obtained compounds hydrolyze in aqueous media, the process being accelerated by metal cations. These studies, accompanied by mechanistic considerations and solid-state moisture and thermal analysis, clarify the structure and behavior of this amino acid Schiff base and shed new light on the role of water in its stability.

Bisphosphonates-much more than only drugs for bone diseases.

α,α-Bisphosphonates (BPs) are well established in the treatment of bone diseases such as osteoporosis and Paget's disease. Their successful application originates from their high affinity to hydroxyapatite. While the initially appreciated features of BPs are already beneficial to many patients, recent developments have further expanded their pleiotropic applications. This review describes the background of the interactions of BPs with bone cells that form the basis of the classical treatment. A better understanding of the mechanism behind their interactions allows for the parallel application of BPs against bone cancer and metastases followed by palliative pain relief. Targeted therapy with bone-seeking BPs coupled with a diagnostic agent in one particle resulted in theranostics which is also described here. For example, in such a system, BP moieties are bound to contrast agents used in magnetic resonance imaging or radionuclides used in positron emission tomography. In addition, another example of the pleiotropic function of BPs which involves targeting the imaging agents to bone tissues accompanied by pain reduction is presented in this work.

Multiwalled carbon nanotube hybrids as MRI contrast agents.

Magnetic resonance imaging (MRI) is one of the most commonly used tomography techniques in medical diagnosis due to the non-invasive character, the high spatial resolution and the possibility of soft tissue imaging. Contrast agents, such as gadolinium complexes and superparamagnetic iron oxides, are administered to spotlight certain organs and their pathologies. Many new models have been proposed that reduce side effects and required doses of these already clinically approved contrast agents. These new candidates often possess additional functionalities, e.g., the possibility of bioactivation upon action of particular stimuli, thus serving as smart molecular probes, or the coupling with therapeutic agents and therefore combining both a diagnostic and therapeutic role. Nanomaterials have been found to be an excellent scaffold for contrast agents, among which carbon nanotubes offer vast possibilities. The morphology of multiwalled carbon nanotubes (MWCNTs), their magnetic and electronic properties, the possibility of different functionalization and the potential to penetrate cell membranes result in a unique and very attractive candidate for a new MRI contrast agent. In this review we describe the different issues connected with MWCNT hybrids designed for MRI contrast agents, i.e., their synthesis and magnetic and dispersion properties, as well as both in vitro and in vivo behavior, which is important for diagnostic purposes. An introduction to MRI contrast agent theory is elaborated here in order to point to the specific expectations regarding nanomaterials. Finally, we propose a promising, general model of MWCNTs as MRI contrast agent candidates based on the studies presented here and supported by appropriate theories.

Studies on the redox activity of iron N,O-complexes: Potential T1-contrast agents.

OBJECTIVES: The goal of this study was to determine the redox activity of iron (ethylenebis[2-(o-hydroxyphenyl)glycine]) (EHPG) and (ethylenebis[2-(o-hydroxybenzyl)glycine]) (EHBG) (N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid) derivative complexes and of some N,O-salan complexes of iron. The hexadentate chelate (EHPG and EHBG) ligands varied in their substituents (polar OMe, NHAc, or lipophilic Ph), while the latter had different charge and lipophilicity. The low redox activity of these complexes is important in their potential applications as magnetic resonance imaging contrast agents. METHODS: Redox activity was assessed in the entire Haber-Weiss cycle and separately in the Fenton reaction. The spin-trapping method with 5,5-dimethyl-1-pyrroline-N-oxide monitored in electron paramagnetic resonance was used. The standard Mn marker was applied as a reference for quantitative analysis. Additionally, ascorbate oxidation was analyzed with UV-Vis spectrophotometry. RESULTS: Both the Haber-Weiss cycle and in particular the Fenton reaction showed low redox activity of the studied complexes, which did not exceed 30% of [Fe(EDTA)]- or FeCl3 activity. The N,O-salan complexes expressed even lower activity, i.e. 10-20% activity of [Fe(EDTA)]-. DISCUSSION: For the EHPG and EHBG complexes, it is likely that hydrophobicity and the possibility of H-bond formation play a major role in the resulting redox effects. For this reason, chelates equipped with phenyl groups in the majority belong to less redox-active complexes. For N,O-salan complexes, activity is not correlated with the charge of the coordination sphere, but again, the highly hydrophobic character of the groups and the non-pendant substituents capable of H-bonding that are present in these ligands limit the affinity of hydrophilic species.

Amalgamation of complex iron(III) ions and iron nanoclusters with MWCNTs as a route to potential T2 MRI contrast agents.

Iron-filled multiwall carbon nanotubes (Fe@MWCNTs) were functionalized toward a variety of potential magnetic resonance imaging contrast agents. Oxidized Fe@MWNCTs were covered with PEG5000 via direct esterification or using acyl chloride derivatives. Alternatively, the latter were functionalized with an aminophenol ligand (Fe@O-MWCNT-L). Moreover, pristine Fe@MWCNTs were functionalized with N-phenylaziridine groups (Fe@f-MWCNT) via [2+1] cycloaddition of nitrene. All of these chemically modified nanotubes served as a vehicle for anchoring Fe(3+) ions. The new hybrids--Fe(III)/Fe@(f-/O-)MWCNTs--containing 6%-14% of the "tethered" Fe(3+) ions were studied in terms of the acceleration of relaxation of water protons in nuclear magnetic resonance. The highest transverse relaxivity r2=63.9±0.9 mL mg(-1) s(-1) was recorded for Fe(III)/Fe@O-MWCNT-L, while for Fe(III)/Fe@f-MWCNT, with r2=57.9±2.9 mL mg(-1) s(-1), the highest impact of the anchored Fe(III) ions was observed. The T1/T2 ratio of 30-100 found for all of the nanotube hybrids presented in this work is a very important factor for their potential application as T2 contrast agents. Increased stability of the hybrids was confirmed by ultraviolet-visible spectrophotometry.

EHPG iron(III) complexes as potential contrast contrast agents for MRI.

A series of EHPG ligands and complexes were obtained. The derivatives of choice were p-OMe, 3,4-dimethyl, p-NHAc and p-Ph substituted ones. The complexes were characterized by NMR relaxation decay (T1), EPR and cyclic voltammetry (CV). r1 Relaxivity of the Fe-EHPG-OMe, Fe-EHPG-Ph derivatives was found higher than that of Fe-EHPG. EPR measurements at liquid nitrogen temperature indicate a typical rhombohedral structure for both rac- and meso-diastereoisomers of the EHPG complexes. CV revealed the redox inactivity of the Fe-EHPG complexes at physiological conditions. Interpretation and discussion of the results is presented.

Coupling of C-nitro-NH-azoles with arylboronic acids. A route to N-aryl-C-nitroazoles.

A method for the synthesis of N-aryl-C-nitroazoles is presented. A coupling reaction between variously substituted arylboronic acids and 3(5)-nitro-1H-pyrazole catalyzed by copper salt has been carried out in methanol in the presence of sodium hydroxide to afford the desired N-aryl-C-nitroazoles in good yields. This synthetic route has also been successfully applied to obtain N-phenyl derivatives of 4-nitropyrazole, 2-nitroimidazole, 4(5)-nitroimidazole and 3-nitro-1,2,4-triazole.

A new class of bioactivable self-immolative N,O-ligands.

A hexadentate ligand built on an amine-bis(phenol) skeleton with an aminal, self-immolative moiety is presented. Synthesis of the ligand is convenient and relatively high yielded. Moreover, it enables synthesis of many derivatives, both in the amino-phenol and aminal fragment (various heterocycles). Once the final hexadentate ligand is synthesized via the Katritzky reaction, it becomes prone to hydrolysis. Bioactivation by ß-galactosidase cleaves the glycosylic bond and a spontaneous collapse of the aminal fragment occurs, thus leading to a pentadentate chelate. This bioactivation has been shown for pyrazole, 1,2,4-triazole and benzotriazole derivatives.

1H NMR spectroscopic criteria for the configuration of N-acyl-alpha,beta-dehydro-alpha-amino acid esters.

The diagnostic values of the following three spectral criteria for the configuration of N-acyl-alpha,beta-dehydro-alpha-amino acid esters were examined: (i) the proton at the beta-position at the double bond of a Z-isomer is shielded if compared with the respective E-isomer (delta(beta)Z < delta(beta)E); (ii) the proton at the nitrogen atom is shielded in a Z-isomer in comparison with the corresponding E-isomer (delta(NH)Z < delta(NH)E); and (iii) changing of the solvent from CDCl3 to deuterated trifluoroacetic acid (TFA) causes shielding of the H(beta) vinylic proton of an E-isomer or deshielding of the respective proton of the Z-isomer (delta(CDCl3)E > delta(TFA)E or delta(CDCl3)Z < delta(TFA)Z). The investigations were based on a set of 22 (Z)- and (E)-N-acyl-alpha,beta-dehydro-alpha-amino acid esters of diverse structures, with aliphatic, aromatic and heteroaromatic substituents at the vinylic beta-carbon; most of the examined compounds were hitherto unknown. The application of the substituent effect additivity rule given by Pascual et al. for olefinic protons leads to evidently erroneous configuration assignments of N-acyl-alpha,beta-dehydro-alpha-amino acid esters. The considered criteria were fulfilled for all the examined cases with one exception [the second criterion for the alpha-pivaloylamino-beta-(2-furyl)acrylates]. The comparison of changes in the chemical shifts of H(beta) vinylic protons in CDCl3 and deuterated TFA seems to be the most reliable and useful configuration criterion, as it can be used in the case of a single isomer.

1,4-Bis[(1-methyl-1-phenylethyl)peroxymethyl]benzene.

The title compound, C(26)H(30)O(4), is one of the first alkyl bis-peroxides to be structurally characterized. The molecule lies on a centre of inversion and therefore the terminal phenyl rings are parallel. Although there are three aromatic rings in the molecule, the C-O-O-C torsion angle of 163.10 (10) degrees is close to the value found in Me(3)COOCMe(3).

The formation of a cyclic diacetal of methyl alpha-D-mannopyranoside with a 16-membered macrocyclic loop.

The X-ray structure of a diacetal with a 16-membered macrocyclic loop, which was obtained as a product of the condensation of methyl alpha-D-mannopyranoside and 1,4-bis(2-formylphenoxy)butane is presented together with polymeric compounds resulting from polycondensation; a similar polymer was formed in the reaction of methyl 2,3:4,6-di-O-salicylidene-alpha-D-mannopyranoside with 1,4-dibromobutane.