Formation of intermetallic PdIn nanoparticles: influence of surfactants on nanoparticle atomic structure.

Bimetallic nanoparticles have been extensively studied as electrocatalysts due to their superior catalytic activity and selectivity compared to their monometallic counterparts. The properties of bimetallic materials depend on the ordering of the metals in the structure, and to tailor-make materials for specific applications, it is important to be able to control the atomic structure of the materials during synthesis. Here, we study the formation of bimetallic palladium indium nanoparticles to understand how the synthesis parameters and additives used influence the atomic structure of the obtained product. Specifically, we investigate a colloidal synthesis, where oleylamine was used as the main solvent while the effect of two surfactants, oleic acid (OA) and trioctylphosphine (TOP) was studied. We found that without TOP included in the synthesis, a Pd-rich intermetallic phase with the Pd3In structure initially formed, which transformed into large NPs of the CsCl-structured PdIn phase. When TOP was included, the syntheses yielded both In2O3 and Pd3In. In situ X-ray total scattering with Pair Distribution Function analysis was used to study the formation process of PdIn bimetallic NPs. Our results highlight how seemingly subtle changes to material synthesis methods can have a large influence on the product atomic structure.

Heterocyclic [9]Helicenes Exhibiting Bright Circularly Polarized Luminescence.

We describe a concise synthetic strategy for the preparation of heterocyclic [9]helicenes and a simple preparative-scale protocol for the optical resolution of the resulting M- and P-enantiomers. The helicenes were characterized by single-crystal X-ray diffraction along with a range of spectroscopic and computational techniques. A fluorescence quantum yield of up to 65 % was observed, and the chiroptical properties of both M- and P-helicenes revealed large dissymmetry factors. The circularly polarized luminescence brightness reaches up to 17 M-1 cm-1 , as measured experimentally and verified computationally, which makes this the highest circularly polarized luminescence brightness among heterocyclic helicenes. We describe how chiroptical properties (both circular dichroism and circularly polarized luminescence) can be described and predicted using quantum chemical calculations. The synthetic approach also reveals by-products that originate from internal oxidation reactions, presumably mediated by the close proximity of the π-surfaces in the helicene structure.

Molecular Representations in Machine-Learning-Based Prediction of PK Parameters for Insulin Analogs.

Therapeutic peptides and proteins derived from either endogenous hormones, such as insulin, or de novo design via display technologies occupy a distinct pharmaceutical space in between small molecules and large proteins such as antibodies. Optimizing the pharmacokinetic (PK) profile of drug candidates is of high importance when it comes to prioritizing lead candidates, and machine-learning models can provide a relevant tool to accelerate the drug design process. Predicting PK parameters of proteins remains difficult due to the complex factors that influence PK properties; furthermore, the data sets are small compared to the variety of compounds in the protein space. This study describes a novel combination of molecular descriptors for proteins such as insulin analogs, where many contained chemical modifications, e.g., attached small molecules for protraction of the half-life. The underlying data set consisted of 640 structural diverse insulin analogs, of which around half had attached small molecules. Other analogs were conjugated to peptides, amino acid extensions, or fragment crystallizable regions. The PK parameters clearance (CL), half-life (T1/2), and mean residence time (MRT) could be predicted by using classical machine-learning models such as Random Forest (RF) and Artificial Neural Networks (ANN) with root-mean-square errors of CL of 0.60 and 0.68 (log units) and average fold errors of 2.5 and 2.9 for RF and ANN, respectively. Both random and temporal data splittings were employed to evaluate ideal and prospective model performance with the best models, regardless of data splitting, achieving a minimum of 70% of predictions within a twofold error. The tested molecular representations include (1) global physiochemical descriptors combined with descriptors encoding the amino acid composition of the insulin analogs, (2) physiochemical descriptors of the attached small molecule, (3) protein language model (evolutionary scale modeling) embedding of the amino acid sequence of the molecules, and (4) a natural language processing inspired embedding (mol2vec) of the attached small molecule. Encoding the attached small molecule via (2) or (4) significantly improved the predictions, while the benefit of using the protein language model-based encoding (3) depended on the used machine-learning model. The most important molecular descriptors were identified as descriptors related to the molecular size of both the protein and protraction part using Shapley additive explanations values. Overall, the results show that combining representations of proteins and small molecules was key for PK predictions of insulin analogs.

Invisible strings. The first single crystal of the cTSAP form of [Eu(DOTA)(H2O)]- has an electronic structure similar to one of the reported cSAP forms.

The coordination geometry of lanthanide(III) ions is extremely sensitive to perturbation from the surrounding environment. Changes in the crystal field can be observed as spectral variations in the emission spectra of luminescent lanthanide(III) ions. Europium(III) ions are commonly used to correlate luminescence properties to the crystal field. In solution, kinetically inert complexes as [Ln(DOTA)(H2O)]- can fluctuate and give rise to different diastereomers (H4DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The [Ln(DOTA)(H2O)]- complex adopts a capped square antiprism (cSAP) geometry but can rotate into a capped twisted square antiprism (cTSAP). The time scale of the solution dynamics in [Ln(DOTA)(H2O)]- is shorter than that of luminescence emission, thus, structural averages are observed in the emission spectra. For the first time, we were able to crystallise both forms of the [Eu(DOTA)(H2O)]- diastereomers. The single crystal structure was combined with single crystal luminescence spectroscopy to reveal the electronic structure of Eu(III) in each form of the complex. The coordination geometry of the crystallized cSAP and cTSAP forms of the complex was compared to ideal coordination polyhedra using a continuous symmetry measure in the AlignIt code. The diastereomers of [Eu(DOTA)(H2O)]- all demonstrate very little deviation from ideal geometries yet nearly identical electronic properties were observed from the two different forms.

Long story short: donor set symmetry in [Eu(DOTA)(H2O)]- crystals determines the electronic structure.

Lanthanide complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid DOTA have been studied in great detail due to their use as MRI contrast agents. Since the first report from Desreux in 1980, the Ln[DOTA]- complexes of gadolinium(III) in particular have been thoroughly investigated. The forms of the nine-coordinated [Ln(DOTA)(H2O)]- complexes are well known, and the ligand backbone has been used extensively to create functional MRI contrast agents, luminescent probes, and as a model system for studying the properties of lanthanide(III) ions. In solution, the photophysical properties have been mapped, but as the structures are not known, direct structure-property relationships have not been created. Here, the electronic properties of two Eu[DOTA] compounds (1 and 2) and a Eu[DOTA]-like compound (3) were studied using single-crystal luminescence spectroscopy. The donor set in the three compounds is identical (4N 4O 1O), and using the symmetry deviation value σideal it was shown that the coordination geometry is close to identical. Nevertheless, the electronic properties evaluated using the luminescence spectrum were found to differ significantly between the three compounds. The magnitude of the crystal field splitting was found not to scale with the symmetry of the coordination geometry. It was concluded that the donor set dictates the splitting, yet the structure-property relationships governing the electronic properties of europium(III) ions still elude us.

Health-Related Quality of Life in Colorectal Cancer Patients Treated With Liver Transplantation Compared to Chemotherapy.

Liver transplantation (LT) for patients with non-resectable colorectal liver metastases (CRLM) offers improved survival and has gained increased interest internationally the last years. The aim of this study was to describe the health-related quality of life (HRQoL) in patients with non-resectable CRLM receiving LT and how baseline HRQoL factors affect overall survival (OS). HRQoL data in the SECA (SEcondary CAncer) LT cohort was compared to data obtained from colorectal cancer patients starting first-line chemotherapy for metastatic disease in a clinical trial and data from a Norwegian normal population. HRQoL data from the QLQ-C30 questionnaire used in the SECA LT study and the NORDIC- VII study were reported. The relationship between patient-reported symptom burden at baseline and OS was investigated. In the SECA study longitudinal HRQoL assessment was used to describe the time until definitive deterioration as well as mean values at different time points. Patients in the SECA and NORDIC-VII studies reported similar baseline HRQoL. The median time until definitive deterioration in the transplanted patients was estimated to 36 months. In the SECA study appetite loss and pain at baseline had negative impact on OS (25.3 versus 71.7 months, p = 0.002 and 39.7 versus 71.7 months, p = 0.038, respectively). Despite a relapse in most of the LT patients the Global Health Score (GHS) remained good. Pain, and especially appetite loss at time of transplantation is associated with poor outcome after LT.

Delicate, a study of the structural changes in ten-coordinated La(III), Ce(III), Pr(III), Nd(III), Sm(III) and Eu(III) sulfates.

We recently presented a new method that allows for a direct structural comparison of coordination complexes. The main difference from other methods is that our AlignIt approach uses common scaling and orientation of the complexes when computing the symmetry deviation, σideal, values. Here, six apparently isostructural lanthanide(III) sulfates K6[(Ln)2(SO4)6]/K5Na[(Ln)2(SO4)6] with ten-coordinated lanthanide(III) sites (Ln(O)10) were prepared, and single-crystal structures were determined and compared using the symmetry deviation (σideal) values. The six structures were shown to fall into two groups: Pr(III) and Eu(III) are identical (σideal = 0.04) bar in size. With a maximum σideal of 0.07, the same was found to be true for La(III), Ce(III), Nd(III), Sm(III) structures. The two groups are shown to be significantly different (σideal > 2.7), yet the coordination geometries of all six are best described as bicapped square antiprisms (σideal = 1.15-1.68). The structures differ in more than symmetry as the smaller lanthanides are shown to crystallize with one sodium and five potassium ions, while the larger lanthanides crystallize with six potassium ions. This does not change the structure and we postulate that the structural variation is due to delicate size matching between alkali and lanthanide ions. For the first six lanthanides, this structure is very robust, which is confirmed as seven doped systems readily crystallized. These doped systems were prepared in order to use europium(III) luminescence as a structural probe. Unsurprisingly, only the doped Eu-La and Eu-Ce systems were found to be luminescent. Between these two and all the europium(III) systems, the intricate structural differences were shown to be enough to change both crystal field splitting and luminescence lifetime. We conclude that even in simple dilution experiments, where luminescent lanthanide(III) ions are introduced in 'innocent' hosts materials, the structure can act as a modulator for the observed properties.

We are never ever getting (back to) ideal symmetry: structure and luminescence in a ten-coordinated europium(III) sulfate crystal.

Our theoretical treatment of electronic structures in coordination complexes often rests on assumptions of symmetry. Experiments rarely provide fully symmetric systems to study. In solutions, fluctuations in solvation, variations in conformations, and even changes in constitution occur and complicate the picture. In crystals, lattice distortion, energy transfer, and phonon quenching play a role, but we are able to identify distinct symmetries. Yet the question remains: How is the real symmetry in a crystal compared to ideal symmetries?

[Use of the sentinel lymph node procedure in colorectal cancer].

The use of a sentinel lymph node procedure (SN) in various cancer treatments including breast cancer is well examined. Little is known however, regarding the use of SN in colorectal cancer treatment. In this review, we explain the use of SN and its implications for future colorectal cancer treatment.

Revisiting the assignment of innocent and non-innocent counterions in lanthanide(III) solution chemistry.

Lanthanides are found in critical applications from display technology to renewable energy. Often, these rare earth elements are used as alloys or functional materials, yet access to them is through solution processes. In aqueous solutions, the rare earths are found predominantly as trivalent ions and charge balance dictates that counterions are present. The fast ligand exchange and lack of directional bonding in lanthanide complexes have led to questions regarding the speciation of Ln3+ solvates in the presence of various counterions and the distinction between innocent = non-coordinating and non-innocent = coordinating counterions. There is limited agreement as to which group counterions belong to, which led to this report. By using Eu3+ luminescence, it was possible to clearly distinguish between coordinating and non-coordinating ions. To interpret the results, it was required to bridge the descriptions of ion pairing and coordination. The data-in the form of Eu3+ luminescence spectra and luminescence lifetimes from solutions with varying concentrations of acetate, chloride, nitrate, sulfate, perchlorate and triflate-was contrasted to those obtained with ethylenediaminetetraacetic acid (EDTA4-), which allowed for the distinction between three Ln3+-anion interaction types. It was possible to conclude which counterions are truly innocent (e.g. ClO4- and OTf-) and which clearly coordinate (e.g. NO3- and AcO-). Finally, a considerable amount of data from systems studied under similar conditions allowed the minimum perturbation arising from the inner sphere or outer sphere coordination in Eu3+ complexes to be identified.