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

Oxygen functional groups on MWCNT surface as critical factor Boosting T-2 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

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

<p><b>Objectives</b>: The goal of this study was to determine the redox activity of iron (ethylenebis[2-(<i>o</i>-hydroxyphenyl)glycine]) (EHPG) and (ethylenebis[2-(<i>o</i>-hydroxybenzyl)glycine]) (EHBG) (<i>N</i>,<i>N</i>′-bis(2-hydroxybenzyl)ethylenediamine-<i>N</i>,<i>N</i>′-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.</p> <p><b>Methods</b>: 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-<i>N</i>-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.</p> <p><b>Results</b>: 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)]⁻.</p> <p><b>Discussion</b>: 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.</p

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

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&minus;1 and 10.1% of fluorescence quantum yield for the sodium salt

Green Dynamic Kinetic Resolution—Stereoselective Acylation of Secondary Alcohols by Enzyme-Assisted Ruthenium Complexes

Dynamic kinetic resolution allows for the synthesis of enantiomerically pure asymmetric alcohols. Cyclopentadienyl-derived ruthenium catalysts were immobilized with an ionic liquid, [BMIM][NTf2], on multiwall carbon nanotubes and used for the racemization of chiral secondary alcohols. This successful approach was combined with the enantioselective enzymatic acylation of secondary alcohols (1-phenylethanol and 1-(1-naphthyl)ethanol) using Novozyme® 435. The resulting catalytic system of the ruthenium racemization catalysts and enzymatic acylation led to chiral esters being obtained by dynamic kinetic resolution. The immobilized catalytic system in the ionic liquid gave the same activity of >96% yield within 6 h and a selectivity of 99% enantiomeric excess as the homogeneous system, while allowing for the convenient separation of the desired products from the catalyst. Additionally, the process can be regarded as green, since the efficient reuse of the catalytic system was demonstrated