Photoswitchable hydrazones with pyridine-based rotors and halogen substituents.

The Z,E-photoisomerization of pyridine-based hydrazone switches is typically suppressed due to the presence of pyridine-based rotors. The crystal structures of studied compounds were investigated using theoretical methods combining DFT and QT-AIM calculations to unveil the nature and properties of the intramolecular hydrogen bonding. In this study, we introduced a new series of pyridine-based hydrazones anchored with o-halogen substituents (2-X) and investigated their photoswitching abilities using 1H NMR and UV-Vis spectroscopy. The efficiency of the photoisomerization from initial 2-X-Z to the 2-X-E isomer varied, with the highest yield observed for 2-Cl-E (55%). Our findings, supported by DFT calculations, revealed the formation of a new diastereomer, 2-X-E*, upon back-photoisomerization. We demonstrated that hydrazones from the 2-X series can be reversibly photoswitched using irradiation from the UV-Vis range, and additionally, we explored the effect of the halogen atom on their switching capabilities and also on their thermodynamics and kinetics of photoswitching, determining their molecular solar thermal energy storage potential.

Combining Desferriferrioxamine B and 1-Hydroxy-2-Piperidone ((PIPO)H) to Chelate Zirconium. Solution Structure of a Model Complex of the [89Zr]Zr-DFOcyclo*-mAb Radioimmunoconjugate.

89Zr-immunoPET is a hot topic as 89Zr cumulates the advantages of 64Cu and 124I without their drawbacks. We report the synthesis of a model ligand of a chiral bioconjugable tetrahydroxamic chelator combining the desferriferrioxamine B siderophore and 1-hydroxy-2-piperidone ((PIPO)H), a chiral cyclic hydroxamic acid derivative, and the study by NMR spectroscopy of its zirconium complex. Nuclear Overhauser effect measurements (ROESY) indicated that the complex exists in the form of two diastereomers, in 77 : 23 ratio, resulting from the combination of the central chiralities at the 3-C of the (PIPO)H component and at the Zr4+ cation. The 44 lowest energy structures out of more than 1000 configurations/conformations returned by calculations based on density functional theory were examined. Comparison of the ROESY data and the calculated interatomic H⋅⋅⋅H distances allowed us to select the most probable configuration and conformations of the major complex.

Ratiometric pH-Responsive 19F Magnetic Resonance Imaging Contrast Agents Based on Hydrazone Switches.

Hydrazone-based molecular switches serve as efficient ratiometric pH-sensitive agents that can be tracked with 19F NMR/MRI and 1H NMR. Structural changes induced between pH 3 and 4 lead to signal appearance and disappearance at 1H and 19F NMR spectra allowing ratiometric pH measurements. The most pronounced are resonances of the CF3 group shifted by 1.8 ppm with 19F NMR and a hydrazone proton shifted by 2 ppm with 1H NMR.

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.

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.

A potential method to improve the in vitro cytotoxicity of half-sandwich Os(ii) complexes against A2780 cells.

The [Os(η6-pcym)(dpa)(VP)]PF6 (1-VP) complex contains the histone deacetylase (HDAC) inhibitor valproate (2-propylpentanoate; VP) as a monodentate O-donor ligand and shows ca. 3-fold higher in vitro cytotoxicity against A2780 human ovarian carcinoma cells than its chlorido analogue [Os(η6-pcym)(dpa)Cl]PF6 (1-Cl); pcym = 1-methyl-4-(propan-2-yl)benzene (p-cymene), dpa = 2,2'-dipyridylamine. The complex 1-VP showed promising selectivity towards the A2780 ovarian carcinoma cell line (IC50 = 20.9 µM) over normal human hepatocytes (IC50 > 200.0 µM). Moreover, the complex 1-VP was found to be inactive against MCF-7 (breast adenocarcinoma), PANC-1 (pancreatic adenocarcinoma) and HT-29 (colon carcinoma) up to a concentration of 100 µM. Detailed flow cytometry studies indicated that treatment of A2780 cells with complex 1-VP led to induction of apoptosis, production of reactive oxygen species (ROS) and superoxide (SO) anion radicals, as well as mitochondrial membrane potential depletion and cell cycle perturbations. The microscopic assessment (standard hematoxylin/eosin staining) revealed signs of morphological changes associated with the progression of apoptosis in A2780 cells treated with the IC50 concentration of the complex 1-VP. Consistent with the intracellular production of ROS and SO, the complex 1-VP induced hydroxyl radical formation, as proved by EPR spin trapping experiments. This case study suggests that replacement of the chlorido ligand of half-sandwich Os(ii) complexes by a releasable monodentate biologically active ligand (e.g., VP used in this study) is an effective strategy for the development of novel non-platinum cytotoxic agents.

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.

Fluoride ion complexation by a B(2)/Hg heteronuclear tridentate Lewis acid.

The reaction of [Li(THF)(4)][1,8-mu-(Mes(2)B)C(10)H(6)] with HgCl(2) affords [1,1'-(Hg)-[8-(Mes(2)B)C(10)H(6)](2)] () or [1-(ClHg)-8-(Mes(2)B)C(10)H(6)] (), depending on the stoichiometry of the reagents. These two new compounds have been characterized by (1)H, (13)C, (11)B and (199)Hg NMR, elemental analysis and X-ray crystallography. The cyclic voltammogram of in THF shows two distinct waves observed at E(1/2) -2.31 V and -2.61 V, corresponding to the sequential reductions of the two boron centers. Fluoride titration experiments monitored by electrochemistry suggest that binds tightly to one fluoride anion and more loosely to a second one. Theses conclusions have been confirmed by a UV-vis titration experiment which indicates that the first fluoride binding constant (K(1)) is greater than 10(8) M(-1) while the second (K(2)) equals 5.2 (+/- 0.4) x 10(3) M(-1). The fluoride binding properties of have been compared to those of [1-(Me(2)B)-8-(Mes(2)B)C(10)H(6)] () and [1-((2,6-Me(2)-4-Me(2)NC(6)H(2))Hg)-8-(Mes(2)B)C(10)H(6)] (). Both experimental and computational results indicate that its affinity for fluoride anions is comparable to that of but significantly lower than that of the diborane . In particular, the fluoride binding constants of , and in chloroform are respectively equal to 5.0 (+/- 0.2) x 10(5) M(-1), 1.0 (+/- 0.2) x 10(3) M(-1) and 1.7 (+/- 0.1) x 10(3) M(-1). Determination of the crystal structures of the fluoride adducts [S(NMe(2))(3)][-mu(2)-F] and [S(NMe(2))(3)][-mu(2)-F] along with computational results indicate that the higher fluoride binding constant of arises from a strong chelate effect involving two fluorophilic boron centers.