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Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Despite this, current diagnostic tools are still not satisfactory, lacking sensitivity for early-stage or single-cell diagnosis. This study describes the development of small-molecule tracers for the well-known tumor marker prostate-specific membrane antigen (PSMA). These tracers contain a urea motif for PSMA-targeting and iodinated aromatic moieties to allow detection via X-ray fluorescence imaging (XFI). Tracers with a triiodobenzoyl moiety allowed the specific targeting and successful imaging of PSMA+ cell lines with XFI. The XFI-measured uptake of 7.88 × 10 -18 mol iodine (I) per cell is consistent with the uptake of known PSMA tracers measured by other techniques such as inductively coupled plasma mass spectrometry (ICP-MS). This is the first successful application of XFI to tumor cell targeting with a small-molecule tracer. In addition, iodinated tracers were used for the characterization of quantum dots (QDs) conjugated to PSMA-targeting urea motifs. The resulting targeted QD conjugates were shown to selectively bind PSMA+ cell lines via confocal microscopy. The immobilized iodinated targeting vectors allowed the determination of the tracer/QD ratio via XFI and ICP-MS. This ratio is a key property of targeted particles and difficult to measure by other techniques.

Supraparticles (SPs) consisting of superparamagnetic iron oxide nanoparticles (SPIONs) are of great interest for biomedical applications and magnetic separation. To enable their functionalization with biomolecules and to improve their stability in aqueous dispersion, polymer shells are grown on the SPs' surface. Robust polymer encapsulation and functionalization is achieved via atom transfer radical polymerization (ATRP), improving the reaction control compared to free radical polymerizations. This study presents the emulsion-based assembly of differently sized cubic SPIONs (12-30 nm) into SPs with diameters ranging from ∼200 to ∼400 nm using dodecyltrimethylammonium bromide (DTAB) as the surfactant. The successful formation of well-defined spherical SPs depends upon the method used for mixing the SPION dispersion with the surfactant solution and requires the precise adjustment of the surfactant concentration. After purification, the SPs are encapsulated by growing surface-grafted polystyrene shells via activators generated by electron transfer (AGET) ATRP. The polymer shell can be decorated with functional groups (azide and carboxylate) using monomer blends for the polymerization reaction. When the amount of the monomer is varied, the shell thickness as well as the interparticle distances between the encapsulated SPIONs can be tuned with nanometer-scale precision. Small-angle X-ray scattering (SAXS) reveals that cubic SPIONs form less ordered assemblies within the SPs than spherical SPIONs. As shown by vibrating sample magnetometer measurements, the encapsulated SPs feature the same superparamagnetic behavior as their SPION building blocks. The saturation magnetization ranges between 10 and 30 emu/g and depends upon the nanocubes' size and phase composition.

The influence of the electron density of a bridge connecting two redox centers on both the intervalence hole transfer and the magnetic superexchange was investigated in a series of bridged bis-triarylamine mono- and dications. In this series, the bridge was 2,7-fluorenyl, where the bridge electron density was modified by substituents at the 9-position. For the mixed-valence monocations, the observation of both an intervalence charge transfer (IVCT) band and an absorption band associated with an electron transfer from the bridging fluorene to the triarylamine radical cation centers allowed determination of the electron transfer couplings in the framework of the three-state generalized Mulliken-Hush theory. Comparison of the derived couplings with those obtained from a classical two-state approach demonstrates an enhancement of the electronic coupling which increases with decreasing bridge state energy. For the dicationic diradical counterparts, the singlet-triplet gap (exchange interaction) was determined both experimentally and by quantum chemical methods. Hereby, an increase of antiferromagnetic coupling with a lowering of the bridge state energy by electron donating substituents was observed. Analysis of the involved molecular orbitals suggests that the ferromagnetic coupling is inversely proportional to the square of the bridge energy, which is also supported by the experimental findings. This influence of the bridge state energy on both types of interactions, electron transfer and magnetic exchange, provides a design guideline for fine-tuning the properties of electronically coupled organic redox dyads by variation of the bridge electron density.

A series of triads, consisting of a triarylamine electron donor and a perylene diimide electron acceptor which were attached to two different wings of a triptycene bridging unit, was investigated concerning the dynamics of photoinduced charge separation and charge recombination processes with a particular focus on the involved spin-chemical aspects. Attaching electron-donating or electron-withdrawing substituents to the third wing of the triptycene bridge allowed tuning the electron transfer processes. These processes were investigated via fs-transient absorption spectroscopy and ns-transient absorption spectroscopy in an external magnetic field. The resulting magnetic field-dependent decay dynamics were analysed and modelled using the stochastic Liouville equation which yielded rate constants for the charge recombination and the exchange energy. In combination with a diabatic rate theory and Anderson's perturbative treatment of the exchange energy, these data gave a complete set of rate constants for charge separation and charge recombination from which the diverse electronic couplings between the involved states were derived. These couplings depend linearly on the inverse energy of virtual triptycene bridge states which allows tuning the electron transfer dynamics by modifying the triptycene bridge.

High complex stability and longitudinal relaxivity of Gd-based contrast agents are important requirements for magnetic resonance imaging (MRI) because they ensure patient safety and contribute to measurement sensitivity. Charged and zwitterionic Gd 3+ -complexes of the well-known chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) provide an excellent basis for the development of safe and sensitive contrast agents. In this report, we describe the synthesis of DOTA-NOx, a DOTA derivative with four N-oxide functionalities via "click" functionalization of the tetraazide DOTAZA. The resulting complexes Gd-DOTA-NOx and Eu-DOTA-NOx are stable compounds in aqueous solution. NMR-spectroscopic characterization revealed a high excess of the twisted square antiprismatic (TSAP) coordination geometry over square antiprismatic (SAP). The longitudinal relaxivity of Gd-DOTA-NOx was found to be r 1 =7.7 mm -1  s -1 (1.41 T, 37 °C), an unusually high value for DOTA complexes of comparable weight. We attribute this high relaxivity to the steric influence and an ordering effect on outer sphere water molecules surrounding the complex generated by the strongly hydrated N-oxide groups. Moreover, Gd-DOTA-NOx was found to be stable against transchelation with high excess of EDTA (200 eq) over a period of 36 h, and it has a similar in vitro cell toxicity as clinically used DOTA-based GBCAs., (© 2023 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

Icosahedral carboranes, C 2 B 10 H 12 , have long been considered to be aromatic but the extent of conjugation between these clusters and their substituents is still being debated. m- and p-Carboranes are compared with m- and p-phenylenes as conjugated bridges in optical functional chromophores with a donor and an acceptor as substituents here. The absorption and fluorescence data for both carboranes from experimental techniques (including femtosecond transient absorption, time-resolved fluorescence and broadband fluorescence upconversion) show that the absorption and emission processes involve strong intramolecular charge transfer between the donor and acceptor substituents via the carborane cluster. From quantum chemical calculations on these carborane systems, the charge transfer process depends on the relative torsional angles of the donor and acceptor groups where an overlap between the two frontier orbitals exists in the bridging carborane cluster., (© 2024. The Author(s).)

The study focuses on the structural and photophysical characteristics of neutral and oxidized forms of N-tolanyl-phenochalcogenazines PZX-tolan with X=O, S, Se, and Te. X-ray crystal structure analyses show a pseudo-equatorial (pe) structure of the tolan substituent in the O, S, and Se dyads, while the Te dyad possesses a pseudo-axial (pa) structure. DFT calculations suggest the pe structure for O and S, and the pa structure for Se and Te as stable forms. Steady-state and femtosecond-time resolved optical spectroscopy in toluene solution indicate that the O and S dyads emit from a CT state, whereas the Se and Te dyads emit from a tolan-localized state. The T 1 state is tolan-localized in all cases, showing phosphorescence at 77 K. The heavy atom effect of chalcogens induces intersystem crossing from S 1 to T x , resulting in a decreasing S 1 lifetime from 2.1 ns to 0.42 ps. The T 1 states possess potential for singlet oxygen sensitization with a high quantum yield (ca. 40 %) for the O, S, and Se dyads. Radical cations exhibit spin density primarily localized at the heterocycle. EPR measurements and quasirelativistic DFT calculations reveal a very strong g-tensor anisotropy, supporting the pe structure for the S and Se derivatives., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Stretched electron-donor-bridge-acceptor triads that exhibit intramolecular twisting degrees of freedom are capable of modulating exchange interaction ( J ) as well as electronic couplings through variable π-overlap at the linear bond links, affecting the rate constants of photoinduced charge separation and recombination. Here we present an in-depth investigation of such effects induced by methyl substituents leading to controlled steric hindrance of intramolecular twisting around biaryl axes. Starting from the parent structure, consisting of a triphenyl amine donor, a triptycene (TTC) bridge and a phenylene-perylene diimide acceptor (Me0), one of the two phenylene linkers attached to the TTC was ortho -substituted by two methyl groups (Me2, Me3), or both such phenylene linkers by two pairs of methyl groups (Me23). Photoinduced charge separation ( k CS ) leading to a charge-separated (CS) state was studied by fs-laser spectroscopy, charge recombination to either singlet ground state ( k S ) or to the first excited local triplet state of the acceptor ( k T ) by ns-laser spectroscopy, whereby kinetic magnetic field effects in an external magnetic field were recorded and analysed using quantum dynamic simulations of the spin dependent kinetics of the CS state. Kinetic spectra of the initial first order rate constants of charge recombination ( k ( B )) exhibited characteristic J -resonances progressing to lower fields in the series Me0, Me2, Me3, Me23. From the quantum simulations, the values of the parameters J , k S , k T and k STD , the singlet/triplet dephasing constant, were obtained. They were analysed in terms of molecular dynamics simulations of the intramolecular twisting dynamics based on potentials calculated by density functional theory. Apart from k T , all of the parameters exhibit a clear correlation with the averaged cosine square products of the biaryl angles.

Collaborative manual image analysis by multiple experts in different locations is an essential workflow in biomedical science. However, sharing the images and writing down results by hand or merging results from separate spreadsheets can be error-prone. Moreover, blinding and anonymization are essential to address subjectivity and bias. Here, we propose a new workflow for collaborative image analysis using a lightweight online tool named Tyche. The new workflow allows experts to access images via temporarily valid URLs and analyze them blind in a random order inside a web browser with the means to store the results in the same window. The results are then immediately computed and visible to the project master. The new workflow could be used for multi-center studies, inter- and intraobserver studies, and score validations.

In this communication we describe a helically chiral push-pull molecule named 9,10-dimethoxy-[7]helicene diimide, displaying fluorescence (FL) and circularly polarised luminescence (CPL) over nearly the entire visible spectrum dependent on solvent polarity. The synthesised molecule exhibits an unusual solvent polarity dependence of FL quantum yield and nonradiative rate constant, as well as remarkable g abs and g lum values along with high configurational stability.

Five chiral squaraine dimers were synthesized by fusing chiral indolenine semisquaraines with three different benzobisthiazole bridges. The thereby created squaraine dimers show a strong splitting of the lowest energy absorption bands caused by exciton coupling. The intensities of the two exciton transitions and the energetic splitting depend on the angle of the two squaraine moieties within the chromophore dimer. The electric circular dichroism spectra of the dimers show intense Cotton effects whose sign depends on the used squaraine chromophores. Sizable anisotropies g abs of up to 2.6 × 10 -3 could be obtained. TD-DFT calculations were used to partition the rotational strength into the three Rosenfeld terms where the electric-magnetic coupling turned out to be the dominant contribution while the exciton chirality term is much smaller. This is because the chromophore dimers are essentially planar but the angle between the electric transition dipole moment of one squaraine and the magnetic transition dipole moment of the other squaraine strongly deviates from 90°, which makes the dot product between the two moment vectors and, thus, the rotational strength substantial.

A cavity-shaped linear gold(I) hydroxide complex acts as a platform to access unusual gold monomeric species. Notably, this sterically crowded gold fragment enables the trapping of CO 2 via insertion into Au-OH and Au-NH bonds to form unprecedented monomeric gold(I) carbonate and carbamate complexes. In addition, we succeeded in the identification of the first gold(I) terminal hydride bearing a phosphine ligand. The basic nature of the Au(I)-hydroxide moiety is also explored through the reactivity toward other molecules containing acidic protons such as trifluoromethanesulfonic acid and terminal alkynes.

A cavity-shaped gold(I) complex derived from a bulky tri-(ortho-biaryl)-phosphine ligand shows preferred selectivity towards terminal functionalities in the gold(I)-catalysed hydration of alkynes under mild heating due to a well-defined pocket as catalytic active site. The confinement-induced size-exclusion selectivity investigated for eight alkynes contrasts with other gold(I) complexes bearing bulky phosphine ligands that show reduced selectivity or even similar behaviour towards both internal and terminal alkynes. We also interrogate the potential of gold(III) derivatives for the same catalytic process., (© 2023 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

While spin-orbit coupling does not play a decisive role in the photophysics of unsubstituted perylene diimides (PDI), this changes dramatically when two phenylselenyl or phenyltelluryl substituents were attached to the PDI bay positions. In the series of PhO-, PhS-, PhSe-, and PhTe-substituted PDIs we observed strongly decreasing fluorescence quantum yield as a consequence of strongly increasing intersystem crossing (ISC) rate, measured by transient absorption spectroscopy with fs- and ns-time resolution as well as by broadband fluorescence upconversion. Time-dependent density functional calculations suggest increasing spin-orbit coupling due to the internal heavy-atom effect as the reason for fast ISC. In case of the selenium PDI derivative we found significant singlet oxygen sensitization via the PDI triplet state. The corresponding radical anions of the chalcogen substituted PDIs were also prepared and investigated by optical and EPR spectroscopy. Here, the increasing SOC results in an increase of the g -tensor anisotropy, and of the isotropic g -value in solution, albeit quasirelativistic density functional calculations show only a relatively small fraction of the spin density to be located on the chalcogen atom.

Yamamoto homocoupling of two chiral oxindoles led to the atropo-diastereoselective formation of an axially chiral oxindole dimer. This building block served as the starting material for the syntheses of axially chiral squaraine and merocyanine chromophore dimers. These dimers show pronounced chiroptical properties, this is, outstandingly high ECD signals (Δ ε up to ca. 1500 M -1 cm -1 ) as a couplet with positive Cotton effect for the P -configuration around the biaryl axis and a negative Cotton effect for the M -configuration. All investigated dimers also exhibit pronounced circularly polarised emission with anisotropy values of ca. 10 -3 cgs. Time-dependent density functional calculations were used to analyse the three contributions (local one electron, electric-magnetic coupling, and exciton coupling) to the rotational strength applying the Rosenfeld equation to excitonically coupled chromophores. While the exciton coupling term proves to be the dominant one, the electric-magnetic coupling possesses the same sign and adds significantly to the total rotational strength owing to a favourable geometric arrangement of the two chromophores within the dimer., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A single sub-anesthetic dose of ketamine produces a rapid and sustained antidepressant response, yet the molecular mechanisms responsible for this remain unclear. Here, we identified cell-type-specific transcriptional signatures associated with a sustained ketamine response in mice. Most interestingly, we identified the Kcnq2 gene as an important downstream regulator of ketamine action in glutamatergic neurons of the ventral hippocampus. We validated these findings through a series of complementary molecular, electrophysiological, cellular, pharmacological, behavioral, and functional experiments. We demonstrated that adjunctive treatment with retigabine, a KCNQ activator, augments ketamine's antidepressant-like effects in mice. Intriguingly, these effects are ketamine specific, as they do not modulate a response to classical antidepressants, such as escitalopram. These findings significantly advance our understanding of the mechanisms underlying the sustained antidepressant effects of ketamine, with important clinical implications., Competing Interests: Declaration of interests A.C. and J.P.L. are named on a patent pending for the combined use of retigabine (ezogabine) and ketamine to amplify antidepressant effects to treat depression and related conditions. F.J.T. reports receiving consulting fees from Roche Diagnostics GmbH and Cellarity Inc. and ownership interest in Cellarity, Inc. and Dermagnostix. All other authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A series of donor-acceptor (D-A) macrocyclic dyads consisting of an electron-poor perylene bisimide (PBI) π-scaffold bridged with electron-rich α-oligothiophenes bearing four, five, six and seven thiophene units between the two phenyl-imide substituents has been synthesized and characterized by steady-state UV/Vis absorption and fluorescence spectroscopy, cyclic and differential pulse voltammetry as well as transient absorption spectroscopy. Tying the oligothiophene strands in a conformationally fixed macrocyclic arrangement leads to a more rigid π-scaffold with vibronic fine structure in the respective absorption spectra. Electrochemical analysis disclosed charged state properties in solution which are strongly dependent on the degree of rigidification within the individual macrocycle. Investigation of the excited state dynamics revealed an oligothiophene bridge size-dependent fast charge transfer process for the macrocyclic dyads upon PBI subunit excitation., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Reversible conversion between excited-states plays an important role in many photophysical phenomena. Using 1-(pyren-2'-yl)- o -carborane as a model, we studied the photoinduced reversible charge-transfer (CT) process and the thermodynamic equilibrium between the locally-excited (LE) state and CT state, by combining steady state, time-resolved, and temperature-dependent fluorescence spectroscopy, fs- and ns-transient absorption, and DFT and LR-TDDFT calculations. Our results show that the energy gaps and energy barriers between the LE, CT, and a non-emissive 'mixed' state of 1-(pyren-2'-yl)- o -carborane are very small, and all three excited states are accessible at room temperature. The internal-conversion and reverse internal-conversion between LE and CT states are significantly faster than the radiative decay, and the two states have the same lifetimes and are in thermodynamic equilibrium., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Two macrocyclic architectures comprising oligothiophene strands that connect the imide positions of a perylene bisimide (PBI) dye have been synthesized via a platinum-mediated cross-coupling strategy. The crystal structure of the double bridged PBI reveals all syn-arranged thiophene units that completely enclose the planar PBI chromophore via a 12-membered macrocycle. The target structures were characterized by steady-state UV/Vis absorption, fluorescence and transient absorption spectroscopy, as well as cyclic and differential pulse voltammetry. Both donor-acceptor dyads show ultrafast Förster Resonance Energy Transfer and photoinduced electron transfer, thereby leading to extremely low fluorescence quantum yields even in the lowest polarity cyclohexane solvent., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Most studies about the interaction of nanoparticles (NPs) with cells have focused on how the physicochemical properties of NPs will influence their uptake by cells. However, much less is known about their potential excretion from cells. However, to control and manipulate the number of NPs in a cell, both cellular uptake and excretion must be studied quantitatively. Monitoring the intracellular and extracellular amount of NPs over time (after residual noninternalized NPs have been removed) enables one to disentangle the influences of cell proliferation and exocytosis, the major pathways for the reduction of NPs per cell. Proliferation depends on the type of cells, while exocytosis depends in addition on properties of the NPs, such as their size. Examples are given herein on the role of these two different processes for different cells and NPs., (© The Author(s) 2022.)