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The crystal structure of the title compound, [Ni(C8H20N4)(NO3)]NO3, at room temperature, has monoclinic (P21/n) symmetry. The structure displays intermolecular hydrogen bonding. The nickel displays a distorted bipyramidal geometry with the symmetric bidentate bonded nitrate occupying an equatorial site. The 1,4,7,10-tetraazacyclododecane (cyclen) backbone has the [4,8] configuration, with three nitrogen-bound H atoms directed above the plane of the nitrogen atoms towards the offset nickel atom with the fourth nitrogen-bound hydrogen directed below from the plane of the nitrogen atoms. The nitrate anion O atoms are seen to hydrogen bond to the H atoms bound to the N atoms of the ligand.

In the title salt, [ZnCl(C23H30N4)]NO3, the central ZnII atom of the complex cation is coordinated in a square-pyramidal arrangement by four nitrogen atoms from cyclen (1,4,7,10-tetraazacyclododecane) in the basal plane and one chlorido ligand in the apical position. The anthracene group attached to cyclen contributes to the crystal packing through intermolecular T-shaped π interactions. Additionally, the nitrate anion participates in intermolecular N—H...O hydrogen bonds with cyclen.

In the title dinuclear CuII complex, [Cu2(NO3)(C24H46N8)(H2O)](NO3)3·3H2O, the two CuII molecules both have a square-pyramidal geometry, but the ligands in the axial positions are different: a water molecule and a nitrate ion. All nitrate ions, water molecules, and N—H groups are involved in an intermolecular hydrogen-bond network.

Abstract Background Lead-212 (212Pb, t1/2 = 10.6 h) and lead-203 (203Pb, t1/2 = 51.9 h) are an element-equivalent, or a matched theranostic radioisotope pair that show great potential for application in targeted radionuclide therapy (TRT) and single-photon emission computed tomography (SPECT), respectively. At TRIUMF we have produced both 203Pb and 212Pb using TRIUMF’s TR13 (13 MeV) and 500 MeV cyclotrons, and subsequently purified and evaluated both radioisotopes using a series of pyridine-modified DOTA analogues in comparison to the commercially available chelates DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and TCMC (1,4,7,10-tetraaza-1,4,7,10-tetra(2-carbamoylmethyl)cyclododecane). Results Proton irradiation (12.8 MeV) of natural and enriched thallium-203 (203Tl) targets gave 203Pb saturation yields of 134 ± 25 and 483 ± 3 MBq/μA, respectively. Thorium-228 (228Th, t1/2 = 1.9 y), a by-product of 232Th proton spallation on TRIUMF’s main 500 MeV beamline (beamline 1A, BL1A), was recovered to build a 228Th/212Pb generator with the ability to deliver up to 9–10 MBq of 212Pb daily. Both lead isotopes were purified via solid phase extraction chromatography (Pb resin), and isolated in an acetate form ([203/212Pb]Pb(OAc)2) suitable for direct radiolabeling of chelators and bioconjugates. A series of cyclen-based chelators (herein referred to as DOTA-1Py, -2Py, and -3Py) along with established chelates DOTA and TCMC were evaluated for their ability to complex both 203Pb and 212Pb. All chelates incorporated 212Pb/203Pb efficiently, with higher radiolabeling yields observed for the 212Pb-complexes. Conclusion The production of 203Pb and 212Pb was established using TRIUMF 13 MeV and 500 MeV cyclotrons, respectively. Both production methods provided radiometals suitable for subsequent radiolabeling reactions using known and novel chelates. Furthermore, the novel chelate DOTA-3Py may be a good candidate for biomolecule conjugation and further theranostic 212Pb/203Pb studies.

Objectives. Chlorin and bacteriochlorin photosensitizers are effective agents for cancer photodynamic therapy and fluorescence imaging. They are also excellent chelators forming stable metal complexes. Besides, 64Cu and 109Pd isotopes can serve as emitters for nuclear medicine. Chelation of these metals with cyclen conjugates with chlorin and bacteriochlorin photosensitizers can become a simple and universal strategy for the synthesis of diagnostic and therapeutic radiopharmaceuticals for nuclear medicine. This article reports on the synthesis of similar Cu and Pd complexes of cyclen conjugates with pheophorbide and bacteriopheophorbide and the study of their photophysical properties.Methods. Metalation of cyclen conjugates was carried out with palladium and copper acetates. For bacteriochlorins, 6-O-palmitoyl-L-ascorbic acid was additionally used as a reducing agent. MALDI mass spectrometry, which was carried out on a time-of-flight mass spectrometer Bruker Ultraflex TPF/TOF and a Bruker Daltonics Autoflex II confirmed the structure of the compounds obtained Electronic absorption spectra were obtained on a Shimadzu 3101 spectrophotometer. Fluorescence and phosphorescence spectra were obtained on a FluoTime 300 PicoQuant spectrofluorometer.Results. Photophysical studies of metal complexes showed that the introduction of palladium cations quenches fluorescence and increases the quantum yield of singlet oxygen generation to 0.98 for the chlorin conjugate. Besides, it decreases the quantum yield of fluorescence to 0.10 and increases the quantum yield of singlet oxygen generation to 0.72 for the bacteriochlorin conjugate. Introducing a copper cation to cyclen conjugates with pheophorbide and bacteriopheophorbide leads to photophysical characteristics quenching.Conclusions. Due to the stability of the synthesized metal complexes in acidic media, as well as the short metalation time (5, 20, 10, and 15 minutes) it is reasonable to expect the successful development of effective imaging agents for positron emission tomography and radionuclide therapy. In addition, the residual fluorescence of bacteriochlorins makes it possible to use fluorescence diagnostics in combination with these methods.

Wormlike micelles, which are linear aggregates created by the self-assembly of surfactants, may entangle to form dynamic three-dimensional network-like structures, endowing solutions with considerable macroscopic viscoelasticity. Recently, a pressing need has arisen to research a novel stimuli-responsive worm-like micelle that is efficient and environmentally friendly. CO2 is an inexpensive, abundant, non-toxic, biocompatible, and non-combustible gas, and it is anticipated that CO2 may serve as the trigger for stimuli-responsive worm-like micelles. In this paper, the formation of CO2-switchable pseudo-tetrameric surfactants, which subsequently self-assemble into CO2-switched wormlike micelles, is accomplished using a simple mixing of two commercial reagents, such as stearic acids and cyclen. The rheological characteristics switched by the use of CO2 are cycled between that of a low-viscosity (1.2 mPa·s) fluid and a viscoelastic fluid (worm-like micelles, 3000 mPa·s). This article expands the field of study on stimuli-responsive worm-like micelles.

Abstract Introduction An efficient and cost-effective synthesis of the metal chelating agents that couple to tumor-targeting peptides is required to enhance the process of preclinical research toward the clinical translation of molecular imaging agents. DOTA is one of the most widely used macrocyclic ligands for the development of new metal-based imaging and therapeutic agents owing to its ability to form stable and inert complexes under physiological conditions. Although solid-phase synthesis compatible DOTA-tris-(t-Bu ester) is a commercial product, it is expensive and contain chemical impurities. There is a need to explore new and cost-effective methods for the preparation of metal chelating agents, i.e., DOTA, directly on solid support to facilitate rapid, cost-effective, and high purity preparation of DOTA-linked peptides for imaging and therapy. In the present study, we describe a facile synthetic strategy of DOTA preparation and its linkage to peptides directly on solid-phase support. Methods Bombesin (BN) peptides were functionalized with DOTA chelator prepared from cyclen precursor on solid-phase and from commercial DOTA-tris and radiolabeled with 68Ga. In vitro BN/GRP receptor binding affinities of the corresponding radiolabeled peptides were determined by saturation binding assays on human breast MDA-MB-231, MCF7, T47D, and PC3 prostate cancer cells. Pharmacokinetics were studied in Balb/c mice and in vivo tumor targeting in MDA-MB-231 tumor-bearing nude mice. Results DOTA was prepared successfully from cyclen on solid-phase support, linked specifically to BN peptides and resultant DOTA-coupled peptides were radiolabeled efficiently with 68Ga. The binding affinities of all the six BN peptides were comparable and in the low nanomolar range. All 68Ga-labeled peptides showed high metabolic stability in plasma. These radiopeptides exhibited rapid pharmacokinetics in Balb/c mice with excretion mainly through the urinary system. In nude mice, MDA-MB-231 tumor uptake profiles were slightly different; the BN peptide with Ahx spacer and linked to DOTA through cyclen exhibited higher tumor uptake (2.32% ID/g at 1 h post-injection) than other radiolabeled BN peptides investigated in this study. The same leading BN peptide also displayed favorable pharmacokinetic profile in Balb/c mice. The PET images clearly visualized the MDA-MB-231 tumor. Conclusions DOTA prepared from cyclen on solid-phase support showed comparable potency and efficiency to DOTA-tris in both in vitro and in vivo evaluation. The synthetic methodology described here allows versatile, site-specific introduction of DOTA into peptides to facilitate the development of DOTA-linked molecular imaging and therapy agents for clinical translation.

The cationic ZnII part of aqua(1,4,7,10-tetraazacyclododecane)zinc(II) bis(perchlorate), [Zn(C8H20N4)(H2O)](ClO4)2, exhibits a slightly distorted square-pyramidal coordination environment with a water molecule in the apical position. In the crystal, the macrocyclic ring alternates between two conformations with equal occupancies. Two of the three perchlorate anions are situated about a twofold rotation axis, and one of them shows disorder of the O atoms with occupancies of 0.62 (7) and 0.38 (7). In the crystal, the complexes are connected by intermolecular hydrogen bonding via the perchlorate anions.

Oligonucleotides with the sequences 5′-GTG AUPA TGC, 5′-GCA TAUP CAC and 5′-GUPG ATA UPGC, where UP is 2′-O-propargyl uridine, were subjected to post-synthetic Cu(I)-catalyzed azide–alkyne cycloaddition to attach 1,4,7,10-tetraazacyclododecane (cyclen) and two well-known DNA intercalating dyes: thioxanthone and 1,8-naphthalimide. We propose a convenient cyclen protection–deprotection strategy that allows efficient separation of the resulting polyamine–oligonucleotide conjugates from the starting materials by RP-HPLC to obtain high-purity products. In this paper, we present hitherto unknown macrocyclic polyamine–oligonucleotide conjugates and their hybridization properties reflected in the thermal stability of thirty-two DNA duplexes containing combinations of labeled strands, their unmodified complementary strands, and strands with single base pair mismatches. Circular dichroism measurements showed that the B-conformation is retained for all dsDNAs consisting of unmodified and modified oligonucleotides. An additive and destabilizing effect of cyclen moieties attached to dsDNAs was observed. Tm measurements indicate that placing the hydrophobic dye opposite to the cyclen moiety can reduce its destabilizing effect and increase the thermal stability of the duplex. Interestingly, the cyclen-modified U showed significant selectivity for TT mismatch, which resulted in stabilization of the duplex. We conclude the paper with a brief review and discussion in which we compare our results with several examples of oligonucleotides labeled with polyamines at internal strand positions known in the literature.

A 1,4,7,10-tetraazacyclododecane (cyclen) variant bearing two thiosemicarbazone pendant groups has been prepared. The ligand forms complexes with Mn2+, Co2+ and Zn2+. X-ray crystallography of the Mn2+, Co2+ and Zn2+ complexes showed that the ligand provides a six-coordinate environment for the metal ions. The Mn2+ and Zn2+ complexes exist in the solid state as racemic mixtures of the Δ(δ,δ,δ,δ)/Λ(λ,λ,λ,λ) and Δ(λ,λ,λ,λ)/Λ(δ,δ,δ,δ) diastereomers, and the Co2+ complex exists as the Δ(δ,δ,δ,δ)/Λ(λ,λ,λ,λ) and Δ(λ,λ,λ,δ)/Λ(δ,δ,δ,λ) diastereomers. Density functional theory calculations indicated that the relative energies of the diastereomers are within 10 kJ mol−1. Magnetic susceptibility of the complexes indicated that both the Mn2+ and Co2+ ions are high spin. The ligand was radiolabelled with gallium-68, in the interest of developing new positron emission tomography imaging agents, which produced a single species in high radiochemical purity (>95%) at 90 °C for 10 min.

The crystal structure of the title salt, [Cu(ClO4)(C8H20N4)]ClO4, is reported. The CuII ion exhibits a square-pyramidal geometry and is coordinated by the four N atoms of the neutral 1,4,7,10-tetraazacyclododecane (cyclen) ligand and an O atom from one perchlorate anion, with the second perchlorate ion hydrogen-bonded to one of the amine N atoms of the cyclen ligand. Additional N—H...O hydrogen bonds between the amine H atoms and the coordinating and non-coordinating perchlorate groups create a three-dimensional network structure. Crystals were grown from a concentrated methanol solution at ambient temperature, resulting in no co-crystallization of solvent.

The supramolecular networks derived from the complexation of polyazamacrocycles with halide anions constitute fundamental building blocks of a broad range of modern materials. This study provides insights into the conformational framework that supports the binding of protonated cyclen macrocyles (1,4,7,10-Tetraazacyclododecane) by chloride anions through NHδ+···Cl− interactions. The isolated complex comprised of two cyclen hosts linked by one Cl− anion is characterized by means of infrared action spectroscopy and ion mobility mass spectrometry, in combination with quantum chemical computations. The Cl− anion is found to act as a hinge that bridges the protonated NH2+ moieties of the two macrocycles leading to a molecular tweezer configuration. Different types of conformations emerge, depending on whether the trimer adopts an open arrangement, with significant freedom for internal rotation of the cyclen moieties, or it locks in a folded conformation with intermolecular H-bonds between the two cyclen backbones. The ion mobility collision cross section supports that folded configurations of the complex are dominant under isolated conditions in the gas phase. The IRMPD spectroscopy experiments suggest that two qualitatively different families of folded conformations coexist at room temperature, featuring either peripheral or inner positions of the anion with respect to the macrocycle cavities, These findings should have implications in the growth of extended networks in the nanoscale and in sensing applications.

The development of lanthanide-based luminescent probes with a long emission lifetime has the potential to revolutionize imaging-based diagnostic techniques. By a rational design strategy taking advantage of computational predictions, a novel, water-soluble Eu3+ complex from a cyclen-based ligand bearing 1,3-disubstituted benzo[h]isoquinoline arms was realized. The ligand has been obtained overcoming the lack of reactivity of position 3 of the isoquinoline moiety. Notably, steric hindrance of the heteroaromatic chromophore allowed selective and stoichiometry-controlled insertion of two or three antennas on the cyclen platform without any protection strategy. The complex bears a fourth heptanoic arm for easy conjugation to biomolecules. This new chromophore allowed the sensitization of the metal center either with one or two photons excitation. The suitability as a luminescent bioprobe was validated by imaging BMI1 oncomarker in lung carcinoma cells following an established immunofluorescence approach. The use of a conventional epifluorescence microscope equipped with a linear structured illumination module disclosed a simple and inexpensive way to image confocally Ln-bioprobes by single photon excitation in the 350–400 nm window, where ordinary confocal systems have no excitation sources.

An efficient protocol for the direct synthesis of N-tetraalkylated derivatives of the azamacrocycles cyclam and cyclen has been developed, using a partially miscible aqueous–organic solvent system with propargyl bromide, benzyl bromide, and related halides. The method works most effectively when the reaction mixture is shaken, not stirred. A crystal structure of the N-tetrapropargyl cyclam derivative 1,4,8,11-tetra(prop-2-yn-1-yl)-1,4,8,11-tetraazacyclotetradecane diperchlorate is reported.

Hybrid complexes with N,N′-bis(2-benzimidazolylmethyl)amine and cyclen moieties are novel enzyme mimics and controlled DNA release materials, which could interact with DNA through three models under different conditions. In this paper, the interactions between plasmid DNA and seven different complexes were investigated, and the methods to change the interaction patterns by graphene oxide (GO) or concentrations were also investigated. The cleavage of pUC19 DNA promoted by target complexes were via hydrolytic or oxidative mechanisms at low concentrations ranging from 3.13 × 10−7 to 6.25 × 10−5 mol/L. Dinuclear complexes 2a and 2b can promote the cleavage of plasmid pUC19 DNA to a linear form at pH values below 7.0. Furthermore, binuclear hybrid complexes could condense DNA as nanoparticles above 3.13 × 10−5 mol/L and partly release DNA by graphene oxide with π-π stacking. Meanwhile, the results also reflected that graphene oxide could prevent DNA from breaking down. Cell viability assays showed dinuclear complexes were safe to normal human hepatic cells at relative high concentrations. The present work might help to develop novel strategies for the design and synthesis of DNA controllable releasing agents, which may be applied to gene delivery and also to exploit the new application for GO.