Drug retention after intradiscal administration.

Intradiscal drug delivery is a promising strategy for treating intervertebral disk degeneration (IVDD). Local degenerative processes and intrinsically low fluid exchange are likely to influence drug retention. Understanding their connection will enable the optimization of IVDD therapeutics.

Understanding the Optical Properties of Doped and Undoped 9-Armchair Graphene Nanoribbons in Dispersion.

Graphene nanoribbons are one-dimensional stripes of graphene with width- and edge-structure-dependent electronic properties. They can be synthesized bottom-up in solution to obtain precise ribbon geometries. Here we investigate the optical properties of solution-synthesized 9-armchair graphene nanoribbons (9-aGNRs) that are stabilized as dispersions in organic solvents and further fractionated by liquid cascade centrifugation (LCC).

NMR Methods to Study the Dynamics of SH2 Domain-Phosphopeptide Complexes.

Nuclear magnetic resonance (NMR) spectroscopy is the method of choice for studying the dynamics of biological macromolecules in solution. By exploiting the intricate interplay between the effects of protein motion (both overall rotational diffusion and internal mobility) and nuclear spin relaxation, NMR allows molecular motion to be probed at atomic resolution over a wide range of timescales, including picosecond (bond vibrations and methyl-group rotations), nanosecond (loop motions and rotational diffusion), and microsecond-millisecond (ligand binding, allostery). In this chapter, we describe different NMR pulse schemes (R, R, heteronuclear NOE, and CPMG relaxation dispersion) to characterize the dynamics of SH2 domains.

Methods for Structure Determination of SH2 Domain-Phosphopeptide Complexes by NMR.

Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique to solve the structure of biomolecular complexes at atomic resolution in solution. Small proteins such as Src-homology 2 (SH2) domains have fast tumbling rates and long-lived NMR signals, making them particularly suited to be studied by standard NMR methods. SH2 domains are modular proteins whose function is the recognition of sequences containing phosphotyrosines.

An NMR Study of a 300-kDa AAA+ Unfoldase.

AAA+ ATPases are ubiquitous hexameric unfoldases acting in cellular protein quality control. In complex with proteases, they form protein degradation machinery (the proteasome) in both archaea and eukaryotes. Here, we use solution-state NMR spectroscopy to determine the symmetry properties of the archaeal PAN AAA+ unfoldase and gain insights into its functional mechanism.

The EJC disassembly factor PYM is an intrinsically disordered protein and forms a fuzzy complex with RNA.

The discovery of several functional interactions where one or even both partners remain disordered has demonstrated that specific interactions do not necessarily require well-defined intermolecular interfaces. Here we describe a fuzzy protein-RNA complex formed by the intrinsically unfolded protein PYM and RNA. PYM is a cytosolic protein, which has been reported to bind the exon junction complex (EJC).

Lipase-Mediated Mechanoenzymatic Synthesis of Sugar Esters in Dissolved Unconventional and Neat Reaction Systems.

Mechanochemical and biocatalytic approaches in modern research are two major assets to develop greener processes. In the present study, these modular tools of sustainability are pointed toward the production of versatile and daily employed compounds such as surfactants. Toward this aim, glycolipids, a class of nonionic surfactants composed of ubiquitous and primary metabolites such as sugar and fatty acid moieties, represent a promising alternative to petroleum-derived surface-active agents.

A photoresponsive palladium complex of an azopyridyl-triazole ligand: light-controlled solubility drives catalytic activity in the Suzuki coupling reaction.

Herein, the design and synthesis of a click-derived Pd-complex merged with a photoswitchable azobenzene unit is presented. While in the -form of the switch the complex showed limited solubility, the photogenerated -form rendered the molecule soluble in polar solvents. This light-controllable solubility was exploited to affect the catalytic activity in the Suzuki coupling reaction.

Unsymmetrical Thienopentalenes: Synthesis, Optoelectronic Properties, and (Anti)aromaticity Analysis.

The synthesis and properties of a series of unsymmetrical thienopentalenes are explored, including both monoareno and diareno derivatives. For the synthesis of monoareno pentalenes, a carbopalladation cascade reaction between alkynes and -dibromoolefins was applied. Diareno pentalene derivatives were accessed via gold-catalyzed cyclization of diynes.

Friction-directed self-assembly of Janus lithographic microgels into anisotropic 2D structures.

We present a method for creating ordered 2D structures with material anisotropy from self-assembling micro-sized hydrogel particles (microgels). Microgel platelets of polygonal shapes (hexagon, square, and rhombus), obtained by a continuous scalable lithographic process, are suspended in an aqueous environment and sediment on an inclined plane. As a consequence of gravitational pull, they slide over the plane.

Lipase-Catalyzed Production of Sorbitol Laurate in a "2-in-1" Deep Eutectic System: Factors Affecting the Synthesis and Scalability.

Surfactants, such as glycolipids, are specialty compounds that can be encountered daily in cleaning agents, pharmaceuticals or even in food. Due to their wide range of applications and, more notably, their presence in hygiene products, the demand is continuously increasing worldwide. The established chemical synthesis of glycolipids presents several disadvantages, such as lack of specificity and selectivity.

Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications.

The highly infectious disease COVID-19 caused by the SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail.

Half-sandwich organometallic Ru and Rh complexes of (N,N) donor compounds: effect of ligand methylation on solution speciation and anticancer activity.

A series of half-sandwich polypyridyl complexes was synthesized and compared focusing on structural, cytotoxic and aqueous solution behaviour. The formula of the synthesized complexes is [M(arene)(N,N)Cl]Cl, where M: Ru or Rh, arene: p-cymene, toluene or C5Me5-, (N,N): 2,2'-bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (dmb), 1,10-phenanthroline (phen) or 2,9-dimethyl-1,10-phenanthroline (neo). The structures of five half-sandwich complexes were determined by X-ray crystallography.

Phosphotyrosine couples peptide binding and SHP2 activation via a dynamic allosteric network.

SHP2 is a ubiquitous protein tyrosine phosphatase, whose activity is regulated by phosphotyrosine (pY)-containing peptides generated in response to extracellular stimuli. Its crystal structure reveals a closed, auto-inhibited conformation in which the N-terminal Src homology 2 (N-SH2) domain occludes the catalytic site of the phosphatase (PTP) domain. High-affinity mono-phosphorylated peptides promote catalytic activity by binding to N-SH2 and disrupting the interaction with the PTP.

Cosolute modulation of protein oligomerization reactions in the homeostatic timescale.

Protein oligomerization processes are widespread and of crucial importance to understand degenerative diseases and healthy regulatory pathways. One particular case is the homo-oligomerization of folded domains involving domain swapping, often found as a part of the protein homeostasis in the crowded cytosol, composed of a complex mixture of cosolutes. Here, we have investigated the effect of a plethora of cosolutes of very diverse nature on the kinetics of a protein dimerization by domain swapping.

UV-induced photolysis of polyurethanes.

Waste production associated with the use of non-degradable materials in packaging is a growing cause of environmental concern, with the polyurethane (PU) class being notorious for their lack of degradability. Herein, we incorporate photosensitive ortho-Nitrobenzyl units into PUs to achieve controllable photodegradability. We performed their photolysis in solution and thin films which can inform the design of degradable adhesives.

Tuning the UV spectrum of PAHs by means of different N-doping types taking pyrene as paradigmatic example: categorization valence bond theory and high-level computational approaches.

Tuning of the electronic spectra of carbon dots by means of inserting heteroatoms into the π-conjugated polycyclic aromatic hydrocarbon (PAH) system is a popular tool to achieve a broad range of absorption and emission frequencies. Especially nitrogen atoms have been used successfully for that purpose. Despite the significant progress achieved with these procedures, the prediction of specific shifts in the UV-vis spectra and the understanding of the electronic transitions is still a challenging task.

Chemistry in Times of Artificial Intelligence.

Chemists have to a large extent gained their knowledge by doing experiments and thus gather data. By putting various data together and then analyzing them, chemists have fostered their understanding of chemistry. Since the 1960s, computer methods have been developed to perform this process from data to information to knowledge.

Solid-state NMR spectroscopy for characterization of RNA and RNP complexes.

Ribonucleic acids are driving a multitude of biological processes where they act alone or in complex with proteins (ribonucleoproteins, RNP). To understand these processes both structural and mechanistic information about RNA is necessary. Due to their conformational plasticity RNA pose a challenge for mainstream structural biology methods.

Total synthesis of four stereoisomers of methyl 4,8,12-trimethylpentadecanoate, a major component of the sex pheromone of the stink bug Edessa meditabunda.

The male-produced sex pheromone of the stink bug Edessa meditabunda was previously identified as a mixture of the esters methyl 4,8,12-trimethylpentadecanoate (1) and methyl 4,8,12-trimethyltetradecanoate (2), produced in a ratio of 92 : 8, respectively. Bioassays showed that the synthetic major compound alone is sufficient to elicit a response from females, and that it is as attractive as the natural extract. Here we present a stereoselective synthesis of four stereoisomers of methyl 4,8,12-trimethylpentadecanoate.

Diarylethene moiety as an enthalpy-entropy switch: photoisomerizable stapled peptides for modulating p53/MDM2 interaction.

Analogs of the known inhibitor (peptide pDI) of the p53/MDM2 protein-protein interaction are reported, which are stapled by linkers bearing a photoisomerizable diarylethene moiety. The corresponding photoisomers possess significantly different affinities to the p53-interacting domain of the human MDM2. Apparent dissociation constants are in the picomolar-to-low nanomolar range for those isomers with diarylethene in the "open" configuration, but up to eight times larger for the corresponding "closed" isomers.

H, C, N chemical shift assignments of SHP2 SH2 domains in complex with PD-1 immune-tyrosine motifs.

Inhibition of immune checkpoint receptor Programmed Death-1 (PD-1) via monoclonal antibodies is an established anticancer immunotherapeutic approach. This treatment has been largely successful; however, its high cost demands equally effective, more affordable alternatives. To date, the development of drugs targeting downstream players in the PD-1-dependent signaling pathway has been hampered by our poor understanding of the molecular details of the intermolecular interactions involved in the pathway.

Branching effect on the linear and nonlinear optical properties of styrylpyrimidines.

This contribution aims at investigating the branching effect on the steady state, time resolved fluorescence and two-photon absorption (2PA) properties of dimethylamino and diphenylamino substituted styrylpyrimidine derivatives, by means of a combined experimental and theoretical study. In contrast to classical branched molecules with a triphenylamine central core and electron accepting groups at the periphery, here, branched molecules with reverse topology and different symmetries are examined, namely a styrylpyrimidine group is used as the electron withdrawing core and dimethylamino or diphenylamino donors are incorporated at the periphery. Besides, compared to the great majority of existing branched systems, the herein studied molecules do not have C3 symmetry.

Structure of a Protein-RNA Complex by Solid-State NMR Spectroscopy.

Solid-state NMR (ssNMR) is applicable to high molecular-weight (MW) protein assemblies in a non-amorphous precipitate. The technique yields atomic resolution structural information on both soluble and insoluble particles without limitations of MW or requirement of crystals. Herein, we propose and demonstrate an approach that yields the structure of protein-RNA complexes (RNP) solely from ssNMR data.