Complexation Research Articles

Antibacterial potential of queen pineapple (Ananas comosus (L.) Merr Var. Queen) peel extract on the growth of Lactobacillus acidophilus bacteria

Based on the Global Burden of Disease Study in 2017, the prevalence of caries in each country reached 20% to more than 50%. Caries is formed due to the role of several factors including host, agent (microorganisms), substrate, and time. Bacteria involved in the origin of caries formation such as Lactobacillus group bacteria found in the oral cavity which can cause dental caries, one of which is Lactobacillus acidophilus. The use of natural cleansers is highly recommended to remove residual bacteria as an effort to prevent caries. Queen Pineapple (Ananas comosus (L.) Merr Var. Queen) is a fruit that contains very complex compounds that can act as anticarcinogenic and antibacterial. This study aims to determine the Minimum Bactericidal Concentration (MBC) and Minimum Inhibitory Concentration (MIC) against the growth of Lactobacillus acidophilus bacteria. This type of research was a laboratory experimental type with posttest only control group design. This study used the dilution method of the number of samples, namely concentrations of 0.781%, 1.56%, 3.125%, 6.25%, 12.5%, 25%, 50%, 100%, positive controls and negative controls. This study was conducted 3 times repetition. Manual calculation of the number of bacterial colonies that grow on nutrient agar media and expressed in colony forming units (CFU) which will determine the MBC and MIC. The Shapiro-Wilk test showed a p value> 0.05 at all concentrations and normally distributed data, but when tested for homogeneity the data was not homogeneous so that the non-parametric statistical test continued using the Kruskal Wallis test showing a value of p < 0.05. Conclusion: Colony count results showed that the concentration of 3.12% can inhibit the visible growth of Lactobacillus acidophilus bacteria which is stated as the Minimum Inhibitory Concentration (MIC) and can prevent growth after subculture to antibiotic-free medium at a concentration of 6.25% which is stated as the Minimum Bactericidal Concentration (MBC).

Key Ingredients for the Modeling of Single‐Atom Electrocatalysts

AbstractSingle‐atom catalysis is gaining interest also because of its potential applications in a broad spectrum of electrochemical reactions. The reactivity of single‐atom catalysts (SACs) is typically modeled with first principles approaches taking insight from heterogenous catalysis. An increasing number of studies show that the chemistry of SACs is more complex than often assumed, and shares many aspects in common with coordination chemistry. This evidence raises challenges for computational electrocatalysis of SACs. In this perspective we highlight a few fundamental ingredients that one need to consider to provide reliable predictions on the reactivity of SACs for electrochemical applications. We discuss the role of the local coordination of the metal active phase, the need to use self‐interaction corrected functionals, in particular when systems have magnetic ground states. We highlight the formation of unconventional intermediates with respect to classical metal electrodes, the need to include the stability of SACs in electrochemical conditions and the role of solvation in the analysis of new potential catalytic systems. This brief account can be considered as a tutorial underlining the importance of treating the reactivity of SACs. In fact, neglecting some of these aspects could lead to unreliable predictions failing in the design of new electrocatalysts.

Enantioselective Cascade Reactions of Aminocatalytic Dienamines and Trienamines Initiated by a Cycloaddition Reaction.

Cycloadditions are widely accepted as a group of reactions that rapidly generate molecular complexity. Being highly atom economic and often predictable, these reactions can generate up to four stereogenic centers and two C-C (or C-X) bonds in one reaction step. During the last two decades, asymmetric aminocatalysis has shown to be a successful strategy for controlling stereoselectivity and enabling reactivity of cycloaddition reactions. By increasing the conjugation of the carbonyl species employed, dienamines and trienamines can be catalytically formed. Not only can these facilitate the cycloaddition, often accompanied by high levels of stereocontrol, but they also leave a residual enamine or carbonyl (by hydrolysis) in the cycloadduct. This residual functionality can engage in further intramolecular reactions generating complex cyclic systems in a one-pot cascade manner. In this regard, asymmetric aminocatalysis can add another layer of complexity to the already complex nature of cycloadditions. In this review, we will present the general concept of such reactivity patterns of dienamines and trienamines, and hereafter showcase examples in the literature. We aspire that the chemical community can use these concepts to design new enantioselective aminocatalytic cascade reactions to access enantioenriched, complex compounds, and perhaps use these in complex molecule synthesis.

The Pyrenean Platform for Observation of the Atmosphere: site, long-term dataset, and science

Abstract. The Pyrenean Platform for Observation of the Atmosphere (P2OA) is a coupled plain–mountain instrumented platform in southwestern France. It is composed of two physical sites: the “Pic du Midi” mountaintop observatory (2877 m a.s.l.) and the “Centre de Recherches Atmosphériques” (600 m a.s.l). Both sites are complementarily instrumented for the monitoring of climate-relevant variables and the study of meteorological processes in a mountainous region. The scientific topics covered by P2OA include surface–atmosphere interactions in heterogeneous landscapes and complex terrain, the physics and chemistry of atmospheric trace species at a large scale, the influence of local- and regional-scale emissions and transport on the atmospheric composition, and transient luminous events above thunderstorms. With a large number of instruments and a high hosting capacity, P2OA contributes to atmospheric sciences through (i) building long-term series of atmospheric observations, (ii) hosting experimental field campaigns and instrumental tests, and (iii) educational training in atmospheric observation techniques. In this context, P2OA is part of the French component of the Aerosol, Clouds and Trace Gases Research Infrastructure (ACTRIS-Fr) and also contributes to the Integrated Carbon Observation System (ICOS) research infrastructure and to several European or international networks. Here, we present the complete instrumentation of P2OA and the associated datasets, give a meteorological characterization of the platform, and illustrate the potential of P2OA and its dataset with past or ongoing studies and projects.

Procollagen-lysine 2-oxoglutarate 5-dioxygenases are responsible for 5R-hydroxylysine modification of therapeutic T-cell bispecific monoclonal antibodies produced by Chinese hamster ovary cells

We present a detailed mass spectrometric analysis of three 2 + 1 T-cell bispecific monoclonal antibodies (TCB mAbs), where an unexpected +15.9950 Da mass shift in tryptic peptides was observed. This modification was attributed to the occurrence of 5R-hydroxylysine (Hyl) using a hybrid LC–MS/MS molecular characterization and CRISPR/Cas9 gene deletion approach. The modification was found at various sites within TCB mAbs, with a conspicuous hot spot motif mirroring a prior observation where Hyl was mapped to the CH1–VH Fab domain interface of IgGs. In contrast to the preceding report, our structural modeling analysis on TCB mAbs unveiled substantial differences in the orientation and flexibility of motifs in immediate proximity and across the artificial CH1–VL cross Fab interface and upstream elbow segment. Utilizing a hybrid database search, RNAseq, and a CRISPR/Cas9 knockout methodology in Chinese hamster ovary (CHO) production cell lines, procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) were conclusively identified as the catalyzing enzymes accountable for the 5R-Hyl modification in TCB mAbs. To quantitatively inhibit Hyl formation in TCB mAbs, the activity of all three Chinese hamster PLOD isoenzymes needs to be depleted via CRISPR/Cas9 gene knockout. Moreover, our investigation identified cell culture iron availability, process duration, and clonal variability in CHO cells as elements influencing the levels of Hyl formation in TCB mAbs. This research offers a solution for circumventing Hyl formation in therapeutic complex mAb formats, such as TCB mAbs, produced in CHO cell culture processes, thereby addressing potential technical and biological challenges associated with unintended Hyl modification.

Soil viral–host interactions regulate microplastic-dependent carbon storage

Microplastic is globally regarded as an important factor impacting biogeochemical cycles, yet our understanding of such influences is limited by the uncertainties of intricate microbial processes. By multiomics analysis, coupled with soil chemodiversity characterization and microbial carbon use efficiency (CUE), we investigated how microbial responses to microplastics impacted soil carbon cycling in a long-term field experiment. We showed that biodegradable microplastics promoted soil organic carbon accrual by an average of 2.47%, while nondegradable microplastics inhibited it by 17.4%, as a consequence of the virus-bacteria coadaptations to the microplastics disturbance. In the relevant functional pathways, nondegradable microplastics significantly (P < 0.05) enhanced the abundance and transcriptional activity related to complex carbohydrate metabolism, whereas biodegradable microplastics significantly (P < 0.05) promoted functions involved in amino acid metabolism and glycolysis. Accordingly, viral lysis enhanced in nondegradable microplastics treatments to introduce more complex organic compounds to soil dissolved organic matters, thus benefiting the oligotrophs with high carbon metabolic capabilities in exploitation competition. In contrast, biodegradable microplastics enriched viral auxiliary metabolic genes of carbon metabolism through "piggyback-the-winner" strategy, conferring to dominant copiotrophs, enhanced substrate utilization capabilities. These virus-host interactions were also demonstrated in the corresponding soil plastisphere, which would alter microbial resource allocation and metabolism via CUE, affecting carbon storage consequently. Overall, our results underscore the importance of viral-host interactions in understanding the microplastics-dependent carbon storage in the soil ecosystem.

Synthesis, Characterization, and Therapeutic Potential of Novel Schiff Base Metal Complexes: Nickel(II) and Copper(II) Complexes Based 2‐[(2‐Chloroquinolin‐3‐yl)methylidene]aminobenzenethiol (CQAT)

ABSTRACTThis research focused on the design and comprehensive characterization of two novel transition metal complexes derived from the symmetrical Schiff base 2‐[(2‐chloroquinolin‐3‐yl)methylidene]aminobenzenethiol (CQAT), coordinated with nickel(II) (NiCQAT) and copper(II) (CuCQAT) ions. The structural elucidation of these complexes was achieved through a range of advanced analytical techniques. Thermal analysis revealed the stability and decomposition patterns of the complexes, supporting the identification of their coordination geometries. The collective data indicated that both NiCQAT and CuCQAT complexes adopt octahedral coordination, with the specific formulas [Ni(CQAT)2(H2O)2] and [Cu(CQAT)2(H2O)2], respectively. To complement the experimental findings, density functional theory (DFT) calculations were employed. These theoretical calculations confirmed the proposed molecular structures and provided detailed insights into key quantum chemical parameters, such as HOMO–LUMO energies, molecular orbitals, and electronic distributions, which are crucial for understanding the complexes' reactivity and stability. Furthermore, extensive in vitro biological evaluations were conducted to assess the anti‐inflammatory and antioxidant properties of the synthesized complexes. These assays demonstrated that both NiCQAT and CuCQAT exhibited significantly enhanced bioactivity compared to the free CQAT ligand, suggesting a synergistic effect of metal coordination on the ligand's biological efficacy. To further explore the mode of action, molecular docking studies were performed targeting two key proteins—human cyclooxygenase‐2 (PDB ID: 5IKT) and human peroxiredoxin 2 (PDB ID: 5IJT). The docking simulations provided valuable insights into the binding affinities, interaction energies, and key amino acid residues involved in the binding process, offering a molecular‐level understanding of their potential biological mechanisms. The findings from these multidisciplinary studies highlight the therapeutic potential of CQAT and its nickel and copper complexes, positioning them as promising candidates for further development in the field of medicinal chemistry.

Synthesis, Structure, and Optical Property of Tris(biaryldiyl)metal Complexes Consisting of Group 9 Elements.

We report the synthesis and characterization of tris(biphenyl-2,2'-diyl)metal complexes of trivalent group 9 elements (1M, M = Co, Rh, Ir) and their nonplanarly π-extended analogs, tris(1,1'-binaphthyl-2,2'-diyl)metal complexes (2M, M = Rh, Ir). Single crystal X-ray crystallography reveals the distorted octahedral geometry with an approximate C3 symmetry of trianionic complexes 1M (M = Co, Rh, Ir) and 2M (M = Rh, Ir), which are contacted by three Li+ ions in the crystal. Complex 1Ir exhibits yellow luminescence in THF with a photoluminescence quantum yield (ΦPL) of up to 0.73, along with a distinctive photophysical property, namely, a concentration dependence of the emission wavelength from 530 to 580 nm. This is a characteristic property of 1Ir and has not been observed in its isoelectronic analog, tris(2-phenylpyridinato)iridium(III) (Ir(ppy)3). The concentration-dependent optical properties originate from the dissociation equilibria of Li+ ions from the anionic chromophore. Complex 2Ir also exhibits luminescence at 715 nm in THF, with a notable bathochromic shift from 1Ir through the π-extension. The findings offer insights into the photophysical properties of homoleptic organo-transition metal complexes, providing the foundation for the design of related transition metal complexes.

Solvent- and Concentration-Induced Topological Transformation of a Ruthenium(II)-Based Trigonal Prism to a Triply Interlocked [2] Catenane.

Synthesis of interlocked supramolecular cages has been a growing field of interest due to their structural diversity. Herein, we report the template-free synthesis of a Ru(II) triply interlocked [2] catenane using coordination-driven self-assembly. The self-assembly of a triazine-based tripyridyl donor L (2,4,6-tris(5-(pyridin-4-yl)thiophen-3-yl)-1,3,5-triazine) with a dinuclear Ru(II) acceptor M (Ru2(dhnq)(η6-p-cymene)2)(CF3SO3)2) yielded two distinct structures depending on the solvent and concentration. In methanol, a triply interlocked metalla [2] catenane (MC2) was formed, whereas in nitromethane, a non-interlocked cage (MC1) was obtained. The non-interlocked cage MC1 was gradually converted to MC2 in nitromethane by the increase in the concentration of cage MC1 from 0.5 to 9 mM. The interlocked cage (MC2) was stable after formation and was unaffected by the change in concentration. Notably, the free cage (MC1) exhibited host-guest interactions with polycyclic aromatic aldehydes, stabilizing the non-interlocked structure even at higher concentrations. In contrast, the triply interlocked [2] catenane (MC2) remains stable due to self-penetration and does not encapsulate guest molecules. This work showcases the stimuli-induced irreversible structural transformation of a triangular prismatic cage to its triply interlocked [2] catenane by employing metal-ligand coordination chemistry.

Wine Phenolic Compounds: Chemistry, Functionality and Health Benefits

Wine phenolic compounds, often known as polyphenols, are a diverse group of secondary bioactive compounds derived from grapes. They play a crucial role in defining the sensory characteristics, functionality, and health benefits of wine. This review explores the complex chemistry of these compounds, focusing on key classes such as flavonoids, which include flavanones, flavonols, anthocyanins, and flavan-3-ols, and non-flavonoids, such as hydroxycinnamic acids, hydroxybenzoic acids, and stilbenes. The health benefits of wine phenolics, particularly their antioxidant and anti-inflammatory properties, are also discussed in relation to preventing and reducing the risk of non-communicable diseases (NCDs) such as cardiovascular diseases, cancers, and neurodegenerative conditions. Furthermore, this review summarized the most current data from human population-based research that investigated the bioactivity of these red wine phytochemicals with relevant health benefits for NCDs. Finally, this review proposes some perspectives for future research to better understand the bioavailability, metabolism, and long-term health effects of these compounds.

The Influence of Fluoride Ions on the Forms of Lanthanide Migration in Natural and Polluted Waters of the Lovozero Massif (The Kola Peninsula)

A comprehensive study (monitoring, thermodynamic modeling) of natural and anthropogenically polluted waters of the Lovozero Massif has been carried out. A thermodynamic study of the weathering of the Lovozero Massif within the “water-rock-atmosphere” system at a temperature of 5 °C showed that the elements contained in the rocks of the studied massif influence the formation of the chemical composition of natural waters. It has been established that an increase in the degree of “water-rock” interaction leads to an increase in the concentrations of F−, Cl−, SO42−, and HCO3− in the solution. This affects the mobility of lanthanum, cerium, and other elements due to the formation of complex compounds with them. The relatively high content of fluorine, phosphorus, and HCO3− (weak and medium acids) in the solution promotes the dissolution of silicates while Si, Al, and P are released into the solution. Monitoring of water from a flooded mine in which there is an increase in the degree of interaction of water with rock showed higher pH values for the concentrations of Na, HCO3−, F−, P, Al, Si, V, U, La, and Ce. The conclusions are relevant in the context of the use of groundwater for drinking water supply purposes. The obtained information is useful to evaluate the health of the population of the region under study.

Synthesis, Electrochemistry and Density Functional Theory of Osmium(II) Containing Different 2,2′:6′,2″-Terpyridines

In coordination chemistry, 2,2′:6′,2″-terpyridine is a versatile and extensively studied tridentate ligand. Terpyridine forms stable complexes with a variety of metal ions through coordination sites provided by the three nitrogen atoms in its pyridine rings. This paper presents an electrochemical study on various bis(terpyridine)osmium(II) complexes, addressing the absence of a systematic investigation into their redox behavior. Additionally, a computational chemistry analysis was conducted on these complexes, as well as on eight previously studied osmium(II)-bipyridine and -phenanthroline complexes, to expand both the experimental and theoretical understanding. The experimental redox potentials, Hammett constants, and DFT-calculated energies show linear correlations due to the electron-donating or electron-withdrawing nature of the substituents, as described by the Hammett constants. These substituent effects cause shifts to lower or higher redox potentials, respectively.

The Key Role of Proton‐Responsive Groups in Electrochemical Hydrogen Evolution Reaction

AbstractThe much‐needed global shift from fossil fuels to sustainable energy is driving significant attention towards hydrogen (H2) as a promising alternative. Proton reduction, a process central to H2 production, is a key area of research for this transition. Naturally‐occurring [FeFe] and [NiFe]‐hydrogenase enzymes play vital roles in the reversible production and oxidation of H2. These enzymes feature a proton‐relay unit comprising of pendant amine and thiol groups in the secondary coordination sphere at the active site. This unit accelerates the rate of H2 production/oxidation, making it a focal point for scientific exploration. Efforts are concentrated on mimicking the active sites of these enzymes both structurally and functionally. In this pursuit, many synthetic transition metal complexes with proton‐responsive units at the secondary coordination sphere of the active site mimic the enzyme's behavior. These units facilitate intramolecular metal‐hydride (M−H) generation and H2‐elimination via H+/H−s coupling, leveraging the proton from the pendant functional group and the hydride from the M−H intermediate. This review delves into electrocatalysts featuring pendant proton‐responsive units and their roles in the electrochemical hydrogen evolution reaction (eHER).

Unveiling the Redox Noninnocence of Metallocorroles: Exploring K-Edge X-ray Absorption Near-Edge Spectroscopy with a Multiconfigurational Wave Function Approach.

X-ray absorption near-edge spectroscopy (XANES) is an advanced technique for probing the local electronic structure of catalysts, effectively identifying the noninnocent nature of ligands in transition-metal complexes. Metallocorroles with noninnocent corrole rings exhibit unusual electronic structures that challenge traditional density functional theory (DFT) methods, necessitating more rigorous approaches to describe electron correlation accurately. We explored K-edge XANES spectra of Fe, Mn, and Co metallocorroles using TDDFT and wave function-based methods. This is the first investigation employing multireference methods, specifically RASSCF, RASPT2, and MC-PDFT, to analyze the redox noninnocent nature of metallocorroles reflected in their XANES spectra. We quantified the noninnocent character of the corrole and the oxidation states of the metals, capturing more than singly excited excitations responsible for the pre-edge peak. Our findings demonstrate the importance of these advanced computational techniques for accurately predicting XANES spectra, providing a reliable understanding of the electronic properties of such complexes. This study offers a new strategy for investigating ligand redox noninnocence via integrated experimental and computational XANES.

The Value of Fractal Analysis in Ultrasound Imaging: Exploring Intricate Patterns

Fractal analysis is a mathematical approach employed to study and describe complex patterns and structures across various disciplines, including mathematics, physics, computer science, biology and finance. Introduced by mathematician Benoit Mandelbrot in the 1970s, fractals are intricate, self-similar patterns that repeat at different scales, exhibiting consistent structures upon magnification or reduction. This analysis involves generating fractals through iterative processes or recursive equations, resulting in highly detailed and complex formations. Fractal analysis enhances medical images by removing noise while preserving details and improving diagnostic quality in magnetic resonance and computed tomography scans. However, there is a lack of comprehensive studies on its application in ultrasound imaging, prompting this narrative review to investigate its use and methodology in this context. Selected papers on the use of fractal analysis in ultrasound imaging were analyzed. Out of 186 records screened, 60 duplicates were removed and 28 were discarded. The text content of 98 potentially eligible papers was checked, with 65 not meeting inclusion criteria. Finally, 33 studies were included in the review. Fractal analysis enhances ultrasound imaging by providing detailed tissue texture characterization, aiding in the diagnosis of conditions like breast and lung cancer, osteoporosis and hypertensive disorders in pregnancy. It quantifies biological structure complexity and improves diagnostic accuracy and reliability. This technique supports clinicians in making informed decisions by offering critical insights into various medical conditions.

Effect of the Introduction of ZnII and CdII Ions on EuIII and TbIII Emission in M2Ln2 Heterometallic Molecules With 2‐Furoic Acid Anions

ABSTRACTHeterometallic d‐4f coordination complexes are of paramount interest in modern coordination chemistry because of their potential applications in organic light‐emitting devices and spintronic materials. Here we report the synthesis and thorough investigation of Ln and MLn (M = Zn, Cd; Ln = Sm, Eu, Gd, Tb) molecular complexes based on 2‐furancarboxylic acid anion (Hfur): [Ln2(NO3)2(fur)4(DME)2] (Ln = Eu, Gd, Tb; DME is dimethoxyethane) and [M2Ln2(NO3)2(fur)8(bpy)2] (M = Zn, Cd; Ln = Eu, Gd, Tb, Sm; bpy is 2,2′‐bipyridyl). The structure and isostructural nature of compounds were determined based on the single‐crystal and powder X‐ray diffraction data. The photophysical properties of the obtained compounds were studied in detail: The energies of the triplet levels of the furoate anion and d‐blocks {M(fur)2(bpy)} (M = Zn, Cd), the relaxation times of the excited states, and the quantum yields were determined. Critical step from Ln complexes to ZnLn and CdLn (Ln = Eu, Tb) is accompanied by an increase in quantum yields, which correlates with a change in the energy of the triplet level of the aromatic part of the complexes and with the results of quantum chemical calculations indicating different schemes for the origination of triplet levels in MLn compounds.

A fundamental analysis on PAHs in food products to detect the toxicity index using fuzzy logic system

Polycyclic Aromatic Hydrocarbons (PAHs) are complex chemical compounds that occur naturally in unprocessed food when it is exposed to contaminated air during transportation, natural emission such as volcano, forest fire and through pesticides spray. It is reported by different agencies that there are 16 types of PAHs in which BaP (Benzo[a] pyrene), BaA (Benz[a]anthracene), BbF(Benzo [b] fluoranthene), Chr (Chrysene) are considered to be carcinogenic and it can occur due to different processes. In processed food it occurs due to various processing methods like overheating, incomplete burning, drying etc. The presence of PAH in food is conventionally found through analytical, traditional, and semi-automatic methods. These methods are found to be valuable but expensive and time-consuming. Further, these methods are used only for the detection of PAHs and the toxicity level is measured or identified based on expert knowledge of researchers and the Standards. Therefore, in this research, a simple harmfulness index system has been developed using Fuzzy Logic System(FLS). The proposed system has been designed based on the PAH values of different food and food products. Hence to initiate the study and to determine the significance of the results, PAH data have been collected from different articles that have investigated food products experimentally. These PAH data were analyzed using statistical measures such as Min, Mean, Max, Standard Deviation, Variance and Kurtosis method. Based on the observations from the results, the fuzzy sets were designed with four membership functions for each PAH and the rules were framed. The strength output from the inference engine has been associated with harmfulness index such as normal, low risk, medium risk, and high risk. From the evaluation, it can be observed that 89.72% of the food samples were recognized along with their degree of harmfulness. Also it can be inferred that 11% of the misclassified samples showed clear metrics of their harmfulness with PAH variations.

Synthesis of Methyl 2-((4R)-3-Acryloyl-4-phenyloxazolidin-2-yl)acetates

The chiral oxazolidine moiety is an important core in asymmetric synthesis due to its ability to participate in various stereoselective chemical reactions and because it forms part of more complex and important active compounds. Therefore, in this letter we report a convenient diastereoselective and practical strategy for the synthesis of chiral methyl 2-((4R)-3-acryloyl-4-phenyloxazolidin-2-yl)acetates, starting from (R)-(–)-2-phenylglycinol and methyl propiolate, which were obtained via two simple chemical and stereoselective reactions.

The H2Sxmacropa Series: Increasing the Chemical Softness of H2macropa with Sulfur Atoms to Chelate Radiometals [213Bi]Bi3+ and [203Pb]Pb2+ for Radiopharmaceutical Applications.

The effects of replacing nitrogen with sulfur atoms in the 18-membered macrocycle of the H2macropa chelator on the binding affinity and stability of "intermediate" (radio)metal [203Pb]Pb2+ and [213Bi]Bi3+ complexes are investigated. The 1,4,10,13-tetraoxo-7,16-diazacyclooctadecane backbone was replaced with derivatives containing sulfur in the 1,4- or the 1,4,10,13-positions to yield the novel chelators H2S2macropa (N4O4S2) and H2S4macropa (N4O2S4), respectively. Trends on the nat/203Pb- and nat/213Bi-complex stability constants, coordination chemistry, radiolabeling, and kinetic inertness were assessed via potentiometric titrations, UV-vis spectroscopy, NMR spectroscopy, X-ray crystallography and density functional theory (DFT) calculations. 1H-207Pb NMR spectroscopy confirmed the involvement of backbone S and/or O donors in the metal coordination sphere. Overall, the trend demonstrated that increasing the softness of the donor atoms within the ligand backbone decreased the thermodynamic stability and kinetic inertness of both the Pb2+ and Bi3+ complexes. Conversely, DFT calculations with mock compounds dimethyl ether (DME) and dimethyl sulfide (DMS) demonstrated enhanced affinity of the S atom to both Pb2+ and Bi3+ with DMS compared to DME evinced by large ΔG° values for both Pb2+ and Bi3+ complexes. The decreased stability of Pb/Bi-Sxmacropa (x = 0, 2, 4) upon increased sulfur atom incorporation may be a result of the increased steric strain within the macrocyclic backbone upon sulfur atom introduction. Nonetheless, [203Pb]Pb2+ and [213Bi]Bi3+ labeling (pH = 7, 30 min reaction time; 10-4-10-8 M chelator) resulted in both S2macropa2- and macropa2- attaining similarly high radiolabeling efficiency. Meanwhile, S4macropa2- only possessed the ability to complex [213Bi]Bi3+. Both [203Pb][Pb(macropa)] and [203Pb][Pb(S2macropa)] remained greater than 97% intact when challenged against human serum over 72 h. The results of this study reveal the effects of incorporating sulfur donor atoms into macrocyclic chelators for [203Pb]Pb2+ and [213Bi]Bi3+ radiopharmaceuticals.

Bimetallic Uranium Complexes with 2,6-Dipicolinoylbis(N,N-Dialkylthioureas)

2,6-Dipicolinoylbis(N,N-dialkylthioureas), H2LR, readily react with uranyl salts under formation of monomeric or dimeric complexes of the compositions [UO2(LR)(solv)] (solv = donor solvents such as H2O, MeOH or DMF) or [{UO2(LR)(µ-OMe)}2]2− (1). In such complexes, the uranyl ions are exclusively coordinated by the “hard” O,N,O or N,N,N donor atom sets of the central ligand unit and the lateral sulfur donor atoms do not participate in the coordination. Different conformations have been found for the dimeric anions. The bridging methanolato ligands and the four uncoordinated sulfur atoms can adopt different orientations with respect to the equatorial coordination spheres of the uranyl units. The presence of non-coordinated sulfur atoms offers the opportunity for the coordination of additional, preferably “soft” metal ions. Thus, reactions with [AuCl(PPh3)], lead acetate or acetates of transition metal ions such as Ni2+, Co2+, Fe2+, Mn2+, Zn2+, or Cd2+, were considered for the syntheses of bimetallic complexes. Various oligometallic complexes with uranyl units were prepared: [{UO2(LR)(μ-OMe)(Au(PPh3)}2] (2), [(UO2)3Pb2(LR)4(MeOH)2(μ-OMe)2] (3), [M{UO2(LR)(OAc)}2] (M= Zn, Ni, Co, Fe, Mn or Cd) (R = Et: 5, RR = morph: 6), or [(UO2)(NiI)2(LR)2] (7). The products were extensively studied spectroscopically and by X-ray diffraction.