Evaluation of structurally related acyclic ligands OBETA, EHDTA, and EGTA for stable Mn complex formation.

In recent years, significant research efforts have been dedicated to finding efficient and safe alternatives to the currently used gadolinium (Gd)-based MRI contrast agents. Among the most explored alternatives are paramagnetic chelates of the Earth-abundant Mn, which form a prominent class of metal complexes. The design of Mn complexes with enhanced relaxation properties and improved safety profiles hinges on a delicate balance between thermodynamic and kinetic stability, as well as the presence of coordinated water molecules.

Comprehensive Investigation of [Fe(EDTA)]-Functionalized Derivatives and their Supramolecular Adducts with Human Serum Albumin.

In recent years, the coordination chemistry of high-spin Fe(III) complexes has increasingly attracted interest due to their potential as effective alternatives to Gd(III)-based MRI contrast agents. This paper discusses the results from our study on Fe(III) complexes with two EDTA derivatives, each modified with either one (EDTA-BOM) or two (EDTA-BOM) benzyloxymethylene (BOM) groups on the acetic arm(s). These pendant hydrophobic groups enable the complexes to form noncovalent adducts with human serum albumin (HSA), leading to an observed increase in relaxivity due to the reduction in molecular tumbling.

Improving the In Vivo Stability of [Mn]Mn(II) Complexes with 18-Membered Macrocyclic Chelators for PET Imaging.

We report the [Mn/Mn]Mn(II) complexes of the macrocyclic chelators PYAN [3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane] and CHXPYAN [(4,4,10,10)-3,5,9,11-tetraaza-1,7(2,6)-dipyridina-4,10(1,2)-dicyclohexanacyclododecaphane]. The X-ray crystal structures of Mn-PYAN and Mn-CHXPYAN evidence distorted octahedral geometries through coordination of the nitrogen atoms of the macrocycles. Cyclic voltammetry studies evidence reversible processes due to the Mn(II)/Mn(III) pair, indicating that the complexes are resistant to oxidation.

TRASUTA: The Effect of the Structural Rigidity of a Mesocyclic AAZTA-like Chelating Agent on the Thermodynamic, Kinetic, and Structural Properties of Some Divalent Metal and Ga Complexes.

Mesocyclic chelating agents such as AAZTA and its derivatives have been recently reported to overcome the relatively low thermodynamic stability of metal complexes of acyclic chelating agents and the slow complexation kinetics of macrocyclic chelating agents. This work reports the preparation of a spirobicyclic hexadentate AAZTA-like chelating agent (TRASUTA) and the investigation of the thermodynamic, kinetic, and structural properties of the corresponding chelates with the PET-relevant Ga and selected metal ions. A combination of analytical techniques allowed identification of a coordination isomerization process, involving the coordinating side arms and the inversion of a nitrogen atom and leading to lower thermodynamic and kinetic inertness with respect to mononuclear mesocyclic analogues.

New Salicylanilide Derivatives and Their Peptide Conjugates as Anticancer Compounds: Synthesis, Characterization, and Effect on Glioblastoma.

Pharmacologically active salicylanilides (2-hydroxy--phenylbenzamides) have been a promising area of interest in medicinal chemistry-related research for quite some time. This group of compounds has shown a wide spectrum of biological activities, including but not limited to anticancer effects. In this study, substituted salicylanilides were chosen to evaluate the activity on U87 human glioblastoma (GBM) cells.

Improving the Stability and Kinetic Inertness of Mn(II) Complexes by Increasing the Bridge Length in Bicyclic CDTA-Like Ligands.

Kinetic inertness of Mn(II)-based MRI contrast agents can be improved by increasing the rigidity of the polydentate ligand that tightly coordinate the metal ion. Taking inspiration from the remarkable increase in kinetic inertness of [Mn(CDTA)] compared to [Mn(EDTA)] due to the cyclohexyl backbone rigidity, we devised that bicyclic ligands would further improve the kinetic inertness of the Mn(II) complexes. The length of the alkyl bridge on the cyclohexane ring was varied from methylene (BCH-DTA), ethylene (BCO-DTA) to propylene (BCN-DTA) to evaluate the influence of the different trans-diaminotetraacetate ligands on relaxometric, thermodynamic and kinetic properties of the Mn(II) complexes.

[Gd(HB-DO3A)]: Equilibrium, Dissociation Kinetic and Structural Differences in a Simple Homolog of [Gd(HP-DO3A)] (Prohance).

[Gd(HP-DO3A)] (gadoteridol) as an active compound of ProHance is a widely employed contrast agent in clinical MRI scans in the last 30 years. Recent concerns about the long-term retention of gadolinium-based contrast agents (GBCAs) led to a deeper investigation of the structural features underlying the integrity of the paramagnetic metal complex. Several human and nonclinical studies have noted marked differences among the macrocyclic GBCAs, with the least retention of Gd traces and most rapid elimination consistently being reported for [Gd(HP-DO3A)].

EHDTA: a green approach to efficient Ln-chelators.

The rich coordination chemistry of lanthanoid ions (Ln) is currently exploited in a vast and continuously expanding array of applications. Chelating agents are central in the development of Ln-complexes and in tuning their physical and chemical properties. Most chelators for Ln-complexation are derived from the macrocyclic DOTA or from linear DTPA platforms, both of which arise from fossil-based starting materials.

Radiolabeling of Platelets with Tc-HYNIC-Duramycin for In Vivo Imaging Studies.

Following the in vivo biodistribution of platelets can contribute to a better understanding of their physiological and pathological roles, and nuclear imaging methods, such as single photon emission tomography (SPECT), provide an excellent method for that. SPECT imaging needs stable labeling of the platelets with a radioisotope. In this study, we report a new method to label platelets with Tc, the most frequently used isotope for SPECT in clinical applications.

Thermodynamic and Kinetic Stabilities of Al(III) Complexes with NO Pentadentate Ligands.

Al(III) complexes have been recently investigated for their potential use in imaging with positron emission tomography (PET) by formation of ternary complexes with the radioisotope fluorine-18 (F). Although the derivatives of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) are the most applied chelators for [AlF] labelling and (pre)clinical PET imaging, non-macrocyclic, semi-rigid pentadentate chelators having two N- and three O-donor atoms such as RESCA1 and AMPDA-HB have been proposed with the aim to allow room temperature labelling of temperature-sensitive biomolecules. The paucity of stability data on Al(III) complexes used for PET imaging instigated a complete thermodynamic and kinetic solution study on Al(III) complexes with aminomethylpiperidine (AMP) derivatives AMPTA and AMPDA-HB and the comparison with a RESCA1-like chelator CD3A-Bn (-1,2-diaminocyclohexane--benzyl-,,-triacetic acid).

Characterization of the Fe(III)-Tiron System in Solution through an Integrated Approach Combining NMR Relaxometric, Thermodynamic, Kinetic, and Computational Data.

The Fe(III)-Tiron system (Tiron = 4,5-dihydroxy-1,3-benzenedisulfonate) was investigated using a combination of H and O NMR relaxometric studies at variable field and temperature and theoretical calculations at the DFT and NEVPT2 levels. These studies require a detailed knowledge of the speciation in aqueous solution at different pH values. This was achieved using potentiometric and spectrophotometric titrations, which afforded the thermodynamic equilibrium constants characterizing the Fe(III)-Tiron system.

AAZTA-Like Ligands Bearing Phenolate Arms as Efficient Chelators for Ga Labelling in vitro and in vivo.

The introduction of a phenolate pendant arm in place of an acetate on AAZTA- and DATA-like ligands resulted in hepta- and hexadentate chelators able to form Ga(III) complexes with thermodynamic stability and kinetic inertness higher than that of other Ga(III) complexes based on the parent 6-amino-6-methylperhydro-1,4-diazepine scaffold. In particular, the heptadentate AAZ3A-endoHB with a phenolate arm on an endocyclic N-atom shows a logK of 27.35 and a remarkable resistance to hydroxide coordination up to basic pH (pH>9).

Boosting Bismuth(III) Complexation for Targeted α-Therapy (TAT) Applications with the Mesocyclic Chelating Agent AAZTA.

Targeted α therapy (TAT) is a promising tool in the therapy of cancer. The radionuclide Bi shows favourable physical properties for this application, but the fast and stable chelation of this metal ion remains challenging. Herein, we demonstrate that the mesocyclic chelator AAZTA quickly coordinates Bi at room temperature, leading to a robust complex.

The Correlation Between Platelet Count and Survival in Prostate Cancer.

Purpose: A number of studies have confirmed that elevated platelet count accompanying various solid tumours is associated with worse survival. However, only meagre data are available on the relationship between thrombocytosis and survival in prostate cancer.

Methods: We conducted a retrospective analysis on clinical-pathological data accumulated from 316 patients during on average 51 months of follow-up after laparoscopic prostatectomy performed for prostate cancer.

Host cell targeting of novel antimycobacterial 4-aminosalicylic acid derivatives with tuftsin carrier peptides.

Mycobacterium tuberculosis is an intracellular pathogen and the uptake of the antimycobacterial compounds by host cells is limited. Novel antimycobacterials effective against intracellular bacteria are needed. New N-substituted derivatives of 4-aminosalicylic acid have been designed and evaluated.

Semi-Rigid (Aminomethyl) Piperidine-Based Pentadentate Ligands for Mn(II) Complexation.

Two pentadentate ligands built on the 2-aminomethylpiperidine structure and bearing two tertiary amino and three oxygen donors (three carboxylates in the case of AMPTA and two carboxylates and one phenolate for AMPDA-HB) were developed for Mn(II) complexation. Equilibrium studies on the ligands and the Mn(II) complexes were carried out using pH potentiometry, H-NMR spectroscopy and UV-vis spectrophotometry. The Mn complexes that were formed by the two ligands were more stable than the Mn complexes of other pentadentate ligands but with a lower pMn than Mn(EDTA) and Mn(CDTA) (pMn for Mn(AMPTA) = 7.

[Treatment of neglected gastric bands – review of the literature in relation to a case].

Introduction: Extreme obese (BMI: 50.1) 70 year old male patient after LAGB procedure in 2005, with abdominal wall and port infection underwent subcutaneous incision drainage of the area in December 2020. CT and Gastroscopy confirmed gastric penetration and intramural position of the Band.

Defining the conditions for the development of the emerging class of Fe-based MRI contrast agents.

Fe(iii) complexes are attracting growing interest in chemists developing diagnostic probes for Magnetic Resonance Imaging because they leverage on an endogenous metal and show superior stability. However, in this case a detailed understanding of the relationship between the chemical structure of the complexes, their magnetic, thermodynamic, kinetic and redox properties and the molecular parameters governing the efficacy (relaxivity) is still far from being available. We have carried out an integrated H and O NMR relaxometric study as a function of temperature and magnetic field, on the aqua ion and three complexes chosen as reference models, together with theoretical calculations, to obtain accurate values of the parameters that control their relaxivity.

[Investigation of IL6 expression in patients with colorectal adenocarcinoma].

Unlabelled: Összefoglaló. Bevezetés: A gyulladásos folyamatok és a tumorok kialakulása, illetve progressziója közötti összetett kapcsolat ismert. Az interleukin-6 (IL6) egy pleiotrop gyulladásos citokin, melynek tumorstimuláló és -gátló tulajdonsága is van.

Underlining the Importance of Peripheral Protic Functional Groups to Enhance the Proton Exchange of Gd-Based MRI Contrast Agents.

In this study, we report the synthesis and the equilibrium, kinetic, relaxation, and structural properties of two new Gd complexes based on modified 10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (HPDO3A) designed to modulate the relaxivity at acidic and basic pH due to intra- and intermolecular proton exchange. The presence of a carboxylic or ester moieties in place of the methyl group of HPDO3A allowed differentiation of a protic and nonprotic functional group, highlighting the importance of the formation of an intramolecular hydrogen bond between the coordinated hydroxyl and the carboxylate groups for proton exchange ( = 1.5 × 10 M s, = 1.

Acid-catalyzed proton exchange as a novel approach for relaxivity enhancement in Gd-HPDO3A-like complexes.

A current challenge in medical diagnostics is how to obtain high MRI relaxation enhancement using Gd-based contrast agents (CAs) containing the minimum concentration of Gd ions. We report that in GdHPDO3A-like complexes a primary amide group located in close proximity to the coordinated hydroxyl group can provide a strong relaxivity enhancement at slightly acidic pH. A maximum relaxivity of = 9.

[Elevated platelet count as a possible prognostic marker of survival in patients with head and neck tumours].

Unlabelled: Összefoglaló. Bevezetés: Régóta ismert, hogy a daganatokhoz társuló emelkedett vérlemezkeszám rosszabb túléléssel társul. Fej-nyak tumoros betegek esetében kevés információ áll rendelkezésünkre ezzel az összefüggéssel kapcsolatban.

Cellular Internalization and Inhibition Capacity of New Anti-Glioma Peptide Conjugates: Physicochemical Characterization and Evaluation on Various Monolayer- and 3D-Spheroid-Based Platforms.

Most therapeutic agents used for treating brain malignancies face hindered transport through the blood-brain barrier (BBB) and poor tissue penetration. To overcome these problems, we developed peptide conjugates of conventional and experimental anticancer agents. SynB3 cell-penetrating peptide derivatives were applied that can cross the BBB.

H-Bonding and intramolecular catalysis of proton exchange affect the CEST properties of Eu complexes with HP-DO3A-like ligands.

Eu(HP-DO3A) is present in solution as a mixture of two diastereoisomers whose alcoholic groups are the source of the mobile protons for the CEST effect. The exchange is base catalyzed. Two novel Eu complexes of HP-DO3A-like ligands containing an amino or a carboxylate functionality in the proximity of the -OH groups showed the occurrence of intramolecular catalysis of the prototropic exchange.