Transition metal complexes of the (2,2,2-trifluoroethyl)phosphinate NOTA analogue as potential contrast agents for 19F magnetic resonance imaging.

A new hexadentate 1,4,7-triazacyclononane-based ligand bearing three coordinating methylene-(2,2,2-trifluoroethyl)phosphinate pendant arms was synthesized and its coordination behaviour towards selected divalent (Mg2+, Ca2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+) and trivalent (Cr3+, Fe3+, Co3+) transition metal ions was studied. The ligand forms stable complexes with late divalent transition metal ions (from Co2+ to Zn2+) and the complexes of these metal ions are formed above pH ∼3. A number of complexes with divalent metal ions were structurally characterized by means of single-crystal X-ray diffraction. The complex of the larger Mn2+ ion adopts a twisted trigonally antiprismatic geometry with a larger coordination cavity and smaller torsion of the pendant arms, whereas the smaller ions Ni2+, Cu2+ and Zn2+ form octahedral species with a smaller cavity and larger pendant arm torsion. In the case of the Co2+ complexes, both coordination arrangements were observed. The complexes with paramagnetic metal ions were studied from the point of view of potential utilization in 19F magnetic resonance imaging. A significant shortening of the 19F NMR longitudinal relaxation times was observed: a sub-millisecond range for complexes of Cr3+, Mn2+ and Fe3+ with symmetric electronic states (t2g3 and HS-d5), the millisecond range for the Ni2+ and Cu2+ complexes and tens of milliseconds for the Co2+ complex. Such short relaxation times are consistent with a short distance between the paramagnetic metal ion and the fluorine atoms (∼5.5-6.5 Å). Among the redox-active complexes (Mn3+/Mn2+, Fe3+/Fe2+, Co3+/Co2+, Cu2+/Cu+), the cobalt complexes show sufficient stability and a paramagnetic-diamagnetic changeover with the redox potential lying in a physiologically relevant range. Thus, the Co3+/Co2+ complex pair can be potentially used as a smart redox-responsive contrast agent for 19F MRI.

Influence of proline and hydroxyproline as antimicrobial and anticancer peptide components on the silver(I) ion activity: structural and biological evaluation with a new theoretical and experimental SAR approach.

Silver(I) complexes with proline and hydroxyproline were synthesized and structurally characterized and crystal structure analysis shows that the formulas of the compounds are {[Ag2(Pro)2(NO3)]NO3}n (AgPro) (Pro = L-proline) and {[Ag2(Hyp)2(NO3)]NO3}n (AgHyp) (Hyp = trans-4-hydroxy-L-proline). Both complexes crystallize in the monoclinic lattice with space group P21 with a carboxylate bidentate-bridging coordination mode of the organic ligands Pro and Hyp (with NH2+ and COO- groups in zwitterionic form). Both complexes have a distorted seesaw (C2v) geometry around one silver(I) ion with τ4 values of 58% (AgPro) and 51% (AgHyp). Moreover, the results of spectral and thermal analyses correlate with the structural ones. 1H and 13C NMR spectra confirm the complexes species' presence in the DMSO biological testing medium and their stability in the time range of the bioassays. In addition, molar conductivity measurements indicate complexes' behaviour like 1 : 1 electrolytes. Both complexes showed higher or the same antibacterial activity against Bacillus cereus, Pseudomonas aeruginosa and Staphylococcus aureus as AgNO3 (MIC = 0.063 mM) and higher than silver(I) sulfadiazine (AgSD) (MIC > 0.5 mM) against Pseudomonas aeruginosa. In addition, complex AgPro exerted a strong cytotoxic effect against the tested MDA-MB-231 and Jurkat cancer cell lines (IC50 values equal to 3.7 and 3.0 µM, respectively) compared with AgNO3 (IC50 = 6.1 (5.7) µM) and even significantly higher selectivity than cisplatin (cisPt) against MDA-MB-231 cancer cell lines (SI = 3.05 (AgPro); 1.16 (cisPt), SI - selectivity index). The binding constants and the number of binding sites (n) of AgPro and AgHyp complexes with bovine serum albumin (BSA) were determined at four different temperatures, and the zeta potential of BSA in the presence of silver(I) complexes was also measured. The in ovo method shows the safety of the topical and intravenous application of AgPro and AgHyp. Moreover, the complexes' bioavailability was verified by lipophilicity evaluation from the experimental and theoretical points of view.

Designing Powerful Biindole-Based Inherently Chiral Selectors: Enhancing Enantiodiscrimination by Core Functionalization with Additional Coordination Elements.

Among inherently chiral selectors of axial stereogenicity, usually resulting in very good enantiodiscrimination performances, the biindole-based family has the additional advantage of very easy functionalization of the two nitrogen atoms with a variety of substituents with desirable properties. Aiming to evaluate the possibility of exploiting such feature to enhance the enantiodiscrimination ability of the archetype structure, a series of three inherently chiral monomers were designed and synthesized, characterised by a 2,2'-biindole atropisomeric core conjugated to bithiophene wings enabling fast and regular electrooligomerization, and functionalised at the nitrogen atoms with an ethyl, a methoxyethyl, or a hydroxyethyl substituent. Nitrogen alkylation was also exploited to obtain for the first time the chemical resolution of the biindole selectors without employing chiral HPLC. The enantiodiscrimination ability of the selector series was comparatively evaluated in proof-of-concept chiral voltammetry experiments with a "benchmark" chiral ferrocenyl probe as well as with chiral non-steroidal anti-inflammatory drugs naproxen and ketoprofen. The large enantiomer potential differences for all probes increased in the ethyl < methoxyethyl ≪ hydroxyethyl sequence of selector substituents, supporting our assumption on the beneficial role of an additional coordination element. The powerful hydroxyethyl selector was also applied to ketoprofen in a commercial drug matrix.

Propyl-phthalimide Cyclotricatechylene-Based Chemosensor for Sulfosulfuron Detection: Hybrid Computational and Experimental Approach.

The detection of trace amounts of sulfosulfuron, a pesticide of increasing importance, has become a pressing issue, prompting the development of effective chemosensors. In this study, we functionalized cyclotricatechylene (CTC) with propyl-phthalimide due to the presence of electronegative oxygen and nitrogen binding sites. Our optimized ligand displayed the highest docking score with sulfosulfuron, and experimental studies confirmed a significant fluorescence enhancement upon its interaction with sulfosulfuron. To gain a deeper understanding of the binding mechanism, we introduced density functional theory (DFT) studies. We carried out binding constant, Job's plot, and limit of detection (LOD) calculations to establish the effectiveness of our chemosensor as a selective detector for sulfosulfuron. These findings demonstrate the potential of our chemosensor for future applications in the field of pesticide detection.

Phenyl-Substituted Cibalackrot Derivatives: Synthesis, Structure, and Solution Photophysics.

Three symmetrically and three unsymmetrically substituted cibalackrot (7,14-diphenyldiindolo[3,2,1-de:3',2',1'-ij][1,5]naphthyridine-6,13-dione, 1) dyes carrying two derivatized phenyl rings have been synthesized as candidates for molecular electronics and especially for singlet fission, a process of interest for solar energy conversion. Solution measurements provided singlet and triplet excitation energies and fluorescence yields and lifetimes; conformational properties were analyzed computationally. The molecular properties are close to ideal for singlet fission. However, crystal structures, obtained by single-crystal X-ray diffraction (XRD), are rather similar to those of the polymorphs of solid 1, in which the formation of a charge-separated state followed by intersystem crossing, complemented with excimer formation, outcompetes singlet fission. Results of calculations by the approximate SIMPLE method suggest which ones among the solid derivatives are the best candidates for singlet fission, but it appears difficult to change the crystal packing in a desirable direction. We also describe the preparation of three specifically deuteriated versions of 1, expected to help sort out the mechanism of fast intersystem crossing in its charge-separated state.

Luminescent Cationic Group 4 Metallocene Complexes Stabilized by Pendant N-Donor Groups.

Cationic group 4 metallocene complexes with pendant imine and pyridine donor groups were prepared as stable crystalline [B(C6F5)4]- salts either by protonation of the intramolecularly bound ketimide moiety in neutral complexes [(η5-C5Me5){η5-C5H4CMe2CMe2C(R)═N-κN}MCl] (M = Ti, Zr, Hf; R = t-Bu, Ph) by PhNMe2H+[B(C6F5)4]- to give [(η5-C5Me5){η5-C5H4CMe2CMe2C(R)═NH-κN}MCl]+[B(C6F5)4]- or by chloride ligand abstraction from the complexes [(η5-C5Me5)(η5-C5H4CMe2CH2C5H4N)MCl2] (M = Ti, Zr) by Li[B(C6F5)4]·2.5Et2O to give [(η5-C5Me5)(η5-C5H4CMe2CH2C5H4N-κN)MCl]+[B(C6F5)4]-. Solid state structures of the new compounds were established by X-ray diffraction analysis, and their electrochemical behavior was studied by cyclic voltammetry. The cationic complexes of Zr and Hf, compared to the corresponding neutral species, exhibited significantly enhanced luminescence predominantly from triplet ligand-to-metal (3LMCT) excited states with lifetimes up to 62 µs and quantum yields up to 58% in the solid state. DFT calculations were performed to explain the structural features and optical and electrochemical properties of the complexes.

The cone-tetranitrocalix[4]arene tetraradical tetraanion as an electrochemically generated ligand for heavier alkali metal cations.

Four-electron electrochemical reduction of the cone-tetranitrocalix[4]arene in DMF results in the stable tetraradical tetraanion. The positive shift of the reduction potential of the title compound with an increasing concentration of alkali metal ions is caused by complex formation. The tetranitrocalix[4]arene thus represents an electrochemically generated ligand - a promising receptor/sensor - for alkali metal ions. Observed stoichiometries and corresponding stability constants for individual complexes of potassium, rubidium and caesium were determined. The immobilization and reduction of nitrocalixarenes on the electrode surface offers new applications in electroseparation of alkali metal ions in analytical chemistry.

A study of the planarity of the pyrrolone fragment in 2-isopropyl-2,3-dihydro-1H-isoindol-1-one.

Orthophthalaldehyde (o-phthalaldehyde, OPA) is an aromatic dialdehyde bearing two electron-withdrawing carbonyl groups. The reactions of OPA with primary amines are broadly applied for the synthesis of important heterocyclic compounds with biological relevance. A number of such reactions have been investigated recently and several structures of condensation products have been reported, however, the complex reaction mechanism is still not fully understood and comprises concurrent as well as consecutive reactions. The reaction products depend on the primary amine which reacts with OPA, the reaction environment (solvent) and the proportion of the reactants. The title molecule, C11H13NO, the product of the reaction of OPA with isopropylamine, contains a five-membered pyrrole C4N ring with a carbonyl substituent, which forms part of the isoindolinone unit. Though this pyrrole ring contains one C atom in the sp(3)-hybridized state, it is fairly planar. The title molecule has been compared with similar structures retrieved from the Cambridge Structural Database in order to study this phenomenon. The planarity of this fragment has been explained by the presence of partially delocalized C-C, C-N and C-O bonds, and by an inner angle in the planar pentagonal ring (∼108°), which is close to the ideal tetrahedral value for the sp(3)-hybridized state of the constituent C atom. Due to this propitious angle, this C atom can be present in states intermediate between sp(3)- and sp(2)-hybridized in different structures, while still maintaining the planarity of the ring. There are only weak intermolecular C-H...O hydrogen bonds and C-H...π-electron ring interactions in the structure. In particular, it is the pyrrole ring which is involved in these interactions.

Electrochemical and quantum chemical investigation of tetranitrocalix[4]arenes: molecules with multiple redox centers.

The calix[4]arene skeleton is electrochemically inactive, but it is a useful stable frame for building "smart" molecules and supramolecular assemblies. Suitable substitution on the upper (and/or lower) rim leads to unusual and surprising properties in this system. Polynitrocalix[4]arenes with reducible nitro groups located at the upper rim represent molecules with multiple redox centers where the potential for interactions between them is the focus of interest. The title compounds are promising precursors, e.g., for design and synthesis of sensors. In this work, the stepwise reduction of two tetranitrocalixarenes was investigated electrochemically, and the results were correlated with quantum chemical calculations. The order of individual electron transfers was described as a consequence of molecular geometry. Two independent pairs of equivalent nitro groups were identified whose reduction potential depends upon their respective locations in the molecule. All nitro groups are electronically isolated and thus are reduced independently yielding poly radical ions. The increasing charge has negligible impact on the geometry of the calixarene, which maintains its pinched shape even when carrying an overall molecular charge of -4.