Supramolecular hosts with flexible and controllable shapes offer the prospect of generating new technologies, for example in selective chemical purifications. However, balancing flexibility with the rigidity and fidelity required for successful assembly and guest recognition needed for purification applications remains challenging. Here we report a Zn4L4 tetrahedral cage that interconverts between four diastereomers, driven by binding different guest molecules. The truxene-based cage backbone features inward-pointing methyl groups that enclose guests and differentiate the cavities of otherwise similar diastereomers. The cage switches quantitatively between two T-symmetric diastereomers when exposed to adamantane in varying stoichiometry, and adopts C3-or C2-symmetric diastereomers in the presence of lower-symmetry guests. Cyclic ion-mobility mass spectrometry (cIMS-MS) provided insights into the structure and dynamics of these diastereomeric host-guest complexes, indicating that the cage can retain its stereochemistry following guest release. We leveraged this "shape-memory" effect to achieve the programmable binding of different guests from a mixture, as controlled by pre-programmed host stereochemistry.

Folding for energy storage: peptoid secondary structure influences azobenzene photoisomerization and thermal relaxation, providing a molecular strategy to optimize solar energy capture, storage, and on-demand heat release.

The development of efficient azobenzene-based chromophores for MOlecular Solar Thermal (MOST) energy storage requires improved visible-light absorption and enhanced Z-isomer proportion as well as lifetime. In this work, we investigated two complementary strategies: substitution of one phenyl ring with a thiazole unit to red shift the absorption and grafting the resulting phenylazothiazole (PAT) moiety onto a peptoid backbone to increase lifetime through structural cooperativity. By varying the position of the PAT unit along the peptoid sequence (N-terminal, central, and C-terminal), we assess the impact of molecular architecture on photo and back isomerization. All PAT-peptoids absorb at the edge of the visible region (375-390 nm). Grafting onto the peptoid scaffold enhances the thermal stability of the Z-isomer compared to non-grafted analogues, with C-terminal derivatives exhibiting the longest half-lives. Kinetic analyses reveal that the thermal back-isomerization pathway depends on the chromophore position and local environment. Additionally, solvent polarity and proticity markedly influence both the rate and mechanism of back isomerization. Overall, this study highlights the decisive role of chromophore positioning, sequence design, and solvent environment in tuning the performance of PAT-based MOST systems, providing key guidelines for the rational design of advanced solar thermal energy storage materials.

The development and commercialization of cyclic ion mobility spectrometry (cIMS) instruments has considerably expanded the level of structural details that can be accessed for gaseous ions. Commercial cIMS instruments rely on travelling wave ion mobility spectrometry (TWIMS), a technique that requires calibration of the measured arrival times to enable the determination of collisional cross sections (CCS). Most calibration strategies use peptide mixtures that span a CCS range of approximately 100 – 400 Å2, which can introduce significant inaccuracies when extrapolating to larger ion structures. In addition, TWIMS calibration remains a tedious data processing step that would greatly benefit from automation. Here, we introduce polycIMS, a command-line tool that automates cIMS calibration and generates charge-independent calibration curves covering a broad CCS range from 100 – 1500 Ų, within just 3 minutes on a standard laptop. Calibrated CCS can be determined in He or N 2 ( TW CCS N2→He , TW CCS N2→N2 ) using inexpensive, commercially-available polymer standards and are validated against reported values for more than 50 reference ions. Furthermore, the derived calibration parameters are largely insensitive to collisional activation, making it possible to calibrate multistage cIMS workflows such as slice collision induced unfolding (CIU n ). We anticipate that the simplicity and accessibility of polycIMS will encourage its adoption as a new standard for cIMS calibration.

Abstract Understanding and quantifying activation parameters associated with the gas-phase isomerization kinetics of stereoisomeric ions, such as Z- and E-azobenzene ions, remains a key challenge in modern mass spectrometry. Here, we explore collisional activation as a fast and efficient method to probe isomerization kinetics on QToF instruments equipped with traveling wave-ion mobility spectrometry (TWIMS), such as the Waters Synapt platform. Using sequence-defined peptoids bearing an azobenzene chromophore, we investigate the collision-induced isomerization (CII) of Z-isomer ions into stable E-isomer ions within the Trap Cell–IMS configuration. The extent of Z → E conversion is monitored as a function of the activation voltage (Trap CV), allowing the extraction of kinetic constants based on the known residence time of ions in the Trap Cell. By integrating previously determined gas-phase activation parameters (ΔH‡ and ΔS‡) into a modified Eyring framework, we derived effective temperatures (Teff) that characterize the internal energy distribution of activated ions. The dependence of Teff on Trap CV yields two critical parameters: α, describing the kinetic-to-internal energy conversion efficiency, and T0, the pre-activation ion population temperature. The measured α values are of the same order as those previously derived for protein ions. However, T0 values are found to be system-dependent, which is detrimental for establishing a universal temperature calibration. Ongoing work focuses on expanding the switchable molecule library to map α and T0 across diverse molecular architectures and decipher at the molecular level the origin of these two parameters.

The extraction of phenolic compounds from Cymbopogon citratus (DC.) Stapf (C. citratus) leaves was optimized by applying a response surface methodology (RSM). A centered composite design (CCD) was carried out to analyze the influences of liquid-solid ratio (mL/g), temperature (°C) and extraction time (min) on the extraction yields (EY), the total phenolic contents (TPC), the total flavonoid contents (TFC) and the antioxidant activity (DPPH and FRAP). The aging of the optimized extract was tracked over 150 days under various storage conditions by assessing the reduction in TPC and major flavonoids using colorimetric assays with a UV-vis spectrophotometer and HPLC–ESI–MS quantification, respectively. The optimization results showed that the extraction condition corresponding to 12.4 mL/g of powder at 49.1°C for 157.1 min was the best condition for this combination of variables. Under this condition, extraction yields, TPC, TFC, DPPH and FRAP were 16.5%, 238.8 mg GAE/g, 223.5 mg QE/g, 96.8 µg/mL and 371.2 mg TE/g, respectively. Ten major flavonoids were identified and quantified, of which luteolin 6-C-glucosyl-2"-O-rhamnose and luteolin 7-O-neohesperidoside were the most abundant with 9.7 and 8.3 mg/g of extract, respectively. After 150 days, TPC, flavonoids and antioxidant properties of the dry extract were better preserved (over 75%) than those stored in aqueous and hydroalcoholic solvents at –20°C and 4°C. The results showed that increasing the storage temperature to 25 and 50°C reduced the storage time to 90 and 60 days, respectively. It was also found that di-C-glycosyl flavonoids in the extracts were the most stable compounds compared to O-glycosyl flavonoids. This study highlights the high phenolic compound content of C. citratus extracts, an indicator of its pesticidal potential and a promising source for the biopesticide development.

SUMO1 (small ubiquitin-like modifier 1) is a central feature of post-translational SUMOylation, modifying a broad range of substrate proteins. SUMO1 itself is prone to succination, i.e., a post-translational Michael addition of cysteine onto fumarate, which results in the formation of succinated SUMO1 with modified properties. The present study assesses the structural and gas-phase stability modifications in SUMO1 induced by diethyl fumarate succination using advanced ion mobility spectrometry-mass spectrometry (IMS-MS) techniques. Among them, collision-induced unfolding (CIU) and slice-CIU highlight a modified unfolding process resulting from the creation of specific charge-dipole interactions involving the appended dicarbonyl moiety. The experimental results are further supported by molecular dynamics simulations to understand, at the atomistic level, the mechanisms underlying the CIU of gaseous (derivatized) SUMO1 ions.

SUMO1 (small ubiquitin-like modifier 1) is a central feature of post-translational SUMOylation, modifying a broad range of substrate proteins. SUMO1 itself is prone to succination, i.e., a post-translational Michael addition of cysteine onto fumarate, which results in the formation of succinated SUMO1 with modified properties. The present study assesses the structural and gas-phase stability modifications in SUMO1 induced by diethyl fumarate succination using advanced ion mobility spectrometry-mass spectrometry (IMS-MS) techniques. Among them, collision-induced unfolding (CIU) and slice-CIU highlight a modified unfolding process resulting from the creation of specific charge-dipole interactions involving the appended dicarbonyl moiety. The experimental results are further supported by molecular dynamics simulations to understand, at the atomistic level, the mechanisms underlying the CIU of gaseous (derivatized) SUMO1 ions.

Molecular Solar-Thermal (MOST) systems employ photoswitches that convert solar energy into chemical energy in the form of a metastable isomer and release it as heat upon triggering. An example of such a photoswitch is bicyclooctadiene (BOD), which is converted into its higher energy photoisomer, tetracyclooctane (TCO), by a [2+2] cycloaddition upon UV light irradiation. Despite their potential as MOST candidates due to a high calculated energy storage density of ≈ 1.77 MJ kg-1, BODs are underinvestigated due to their retro Diels-Alder triggered degradation upon heating and very short half-lives of the TCOs in the order of seconds to minutes. Here we report the synthesis of three new acceptor-acceptor BOD isomers substituted with quinoline and the characterisation of their photophysical and photochemical properties. Two of the three BODs exist as a pair of rotational conformers with different absorption profiles, shown experimentally and supported by computational analysis. Calculated storage energies are found to be slightly higher than those of comparable naphthalene-substituted BODs, ranging from 144.0 to 163.6 kJ mol-1. We demonstrate that the substitution position of the quinoline has an influence on key MOST-relevant optical properties including thermal half-lives which range from 13 s to 6 min and the UV-vis absorption spectra. Protonation of the quinoline moiety induces a red shift of ≈ 40 nm in the absorption spectra of each BOD and leads to divergent behaviour upon irradiation, leading to photoswitching, fluorescence, or degradation, depending on the position of the nitrogen in the quinoline ring. These experimental and computational results elucidate how quinoline substitution and nitrogen position govern structure-property relationships in BOD photoswitches, providing design principles for further tuning and improving BODs and other photoswitches towards MOST application.

In recent years, the controlled nature of catalyst transfer polymerizations (CTP) has been significantly investigated and enhanced. Recent studies on Suzuki-Miyaura CTP (SMCTP) revealed that water converts the process into a chain-growth polymerization, while additional Buchwald ligands, particularly RuPhos, further enhance control. This improvement is attributed to the formation of Pd(RuPhos)2 upon catalyst detachment, a bulky species with no affinity for water, which limits catalyst diffusion and suppresses transfer reactions. Despite extensive research on SMCTP, Buchwald ligands remain unexplored in other CTPs, except for RuPhos in Negishimediated polymerization, where transfer steps occur, even in a large extent. Kumada CTP (KCTP) has not been investigated in this context. Here, we report the first KCTP using a Buchwald ligand-based external palladium initiator, 4-methyl benzoatePd(RuPhos)-iodine. First, the controlled nature of the polymerization was investigated and chain transfer and some termination was found. Second, the influence of extra equivalents of ligand severely worsens the controlled nature of the polymerization. These findings elucidate the mechanism of CTP and the role of additional ligand. It is shown that, if the catalysts detaches from the growing polymer chain, the controlled nature of CTP depends on Pd(RuPhos)2 (de)formation and its diffusion. Poor solvent affinity to the ligated Pd-catalyst, as in aqueous mixtures (SMCTP), restricts diffusion and maintains control. In contrast, other (dry) organic solvents allow diffusion, reducing control despite inactive species formation. This work offers a mechanistic framework that may be extended to other catalyst-ligand-polymer combinations, although its broader generalization will require further experimental validation.

Interest in photosensitive molecules has increased significantly over the past decade, with particular attention given to photoswitchable systems. Among these, azobenzene stands out as a reference compound due to its broad range of applications, in particular for solar energy storage. While the trans-to-cis photoisomerization has been relatively well characterized, the reverse cis-to-trans isomerization remains a complex process potentially involving multi-state physics. In this study, we compile recent theoretical advances aimed at modeling this process and introduce, through the spin-flip time-dependent density functional theory (SF-TDDFT) approach combined with the semi-classical Marcus equation, a fast and efficient method to investigate the mechanisms of thermal back-isomerization of azo derivatives. By comparing various exchange-correlation functionals with CASPT2 reference data, we demonstrate that the PBE0(D3BJ) functional provides an accurate description for the non-adiabatic rotational pathway. We successfully reproduce the experimental values (88.6 vs. 88.3 kJ mol(-1) for the experimental enthalpy of activation, and -53.0 vs. -50.2 J mol(-1) K-1 for the experimental entropy of activation) for azobenzene, thus motivating the extension of this methodology to other azo derivatives. This approach can be further generalized to a broader class of azo-based photo-switches in future studies.

SUMO1 (small ubiquitin-like modifier 1) is a key protein involved in the post-translational modification of a wide range of substrate proteins. SUMOylation plays a pivotal role in regulating various cellular processes such as protein localization, functional modulation, and complex formation. Notably, SUMO1 contains a cysteine residue in its sequence, making it susceptible to succination, i.e., a Michael addition of cysteine onto fumarate, forming a succinated cysteine. This could occur under conditions of elevated intracellular fumarate concentration, a hallmark of metabolic dysregulation. To investigate this hypothesis, we employ a multidisciplinary approach integrating advanced analytical techniques such as mass spectrometry (including liquid chromatography, ion mobility spectrometry, and hydrogen-deuterium exchange experiments), circular dichroism spectroscopy, and molecular dynamics simulations. We demonstrate that SUMO1 undergoes succination in vitro, leading to important conformational changes. These findings provide insights into the susceptibility of SUMO1 to metabolic alterations.

Starfish play a crucial role as extraordinary predators in marine ecosystems. They often prey on bivalves, which serve as primary economic resources in certain regions, making their management a top priority. As a result, cleaning operations have been conducted to remove starfish from the coasts, leading to the accumulation of significant waste. Within the context of the circular economy, there is potential for valorizing starfish, transforming them from waste products into valuable resources. However, before doing so, it is essential to analyze the contaminants that starfish can accumulate. To address this, a study was conducted to analyze pollutants in two species of starfish: Marthasterias glacialis and Asterias rubens, collected from the Galician Spanish shores. The goal was to assess their suitability for use as animal feed or fertilizer in agriculture. The study employed optimized methodologies to analyze trace elements, saponins, marine toxins and persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and polycyclic aromatic hydrocarbons (PAHs). The validated protocols for determining these contaminants in starfish showed an acceptable performance in detection, showing the quality parameters of the analytical analysis (recoveries, precision, limit of detection (LOD) and quantification (LOQ)). Results indicated that concentrations of the legislated contaminants in the starfish samples from the Galician shores did not exceed the current EU legislation standards. Consequently, in terms of toxicology, starfish matrix could be considered a suitable raw material for the use in animal feed or as crop fertilizer.

Flavonoids are probable major contributors to the radical scavenging activity in Ecuadorian quinoa leaves, both from the bitter genotype (Chimborazo) and sweet varieties. In this study, we extracted these compounds using a simple, rapid (10 min), and environmentally friendly method based on deep eutectic solvents (DES). Extractions were performed in a ball mixer mill at room temperature with a eutectic mixture of choline chloride-glycerol-water at a molar ratio, of 1:2:1 and compared with classical methanol extraction. Both extracts were characterized using high-performance thin-layer chromatography and liquid chromatography-tandem mass spectrometry-based methods. Regardless of the type of solvent used (conventional or green solvent), quercetin and kaempferol glycosides were found as the major flavonols in sweet and bitter quinoa leaves. DES extract contains a higher amount of quercetin glycosides than methanol and shows a higher capacity to stabilize the quinoa radical scavengers compared to conventional solvent (liquids extracts-conservation for up to 4 months at 5 degrees C). The present research indicates that DES represent an efficient green media for the stabilization of phenolic compounds from quinoa leaves and has the potential as a possible alternative to organic solvents. Our work opens new perspectives for the development of high-added value products based on quinoa leaves for pharmaceutical, nutraceutical and agro-food applications.

Artificial enzymes based on polystyrene copolymers featuring a metal complex within their structure, so-called single-chain nanoparticles (SCNPs), are being explored as hybrid heterogeneous/homogeneous catalysts. Using styrene (derivative) building blocks, SCNP precursor copolymers decorated with pendent triphenylphosphine ligands complexed with catalytically active gold motifs have recently been reported. It is highly challenging to determine the location and orientation of the functional groups - including the catalytic center - the coil geometry, and even the macromolecular architecture within these complex precursors via conventional analytical techniques. The use of ion mobility mass spectrometry (IMS-MS) combined with molecular dynamics (MD) simulations is emerging as a way to establish the structure of gaseous ions, including the description of the secondary interactions responsible for the folding. IMS-MS is used to separate intricate polymer mixtures, while providing structural information through collisional cross section (CCS) determination. MD simulations are used to assign a detailed internal structure to the conformations sampled by IMS-MS by comparing the experimental CCS with the theoretical values computed for the MD structures. In the present contribution, we provide an in-depth investigation of the conformation of gaseous Au-functionalized copolymer ions composed of three different monomer units, i.e., styrene, styrene-CH2-OH and styrene-PPh2-AuCl, and those bearing a TEMPO unit as the initiator end group. For the styrene/styrene-CH2-OH copolymer ions, an H-bond between protonated TEMPO and a styrene-CH2-OH unit is responsible for the ultimate folding of the polymer ions with the charge settled at the center of the globular ions. When incorporating the triphenylphosphine-AuCl unit, a strong H-bond between the chlorine atom and protonated TEMPO is detected. However, the steric hindrance around the triphenylphosphine ligand prevents the charge from being incorporated into the core of the globular ions.

Storing solar energy in chemical bonds through the reversible isomerization of UV-vis absorbing molecules offers a promising approach to energy storage. These molecules form high-energy photoisomers, which can store energy if kinetically protected by a significant activation barrier against spontaneous thermal back-isomerization. In this study, we compare the back-isomerization kinetic parameters (ΔH‡ and ΔS‡) of model azobenzene-based photoswitches in solution with those obtained in the gas phase using an original tandem ion mobility mass spectrometer. Our findings show that the activation enthalpy is well-reproduced from the solution phase to the gas phase, whereas the activation entropy is significantly affected by the absence of solvent, revealing further different relaxation mechanisms.

Elucidating the topology of host-guest complexes is essential for the rational design of supramolecular assemblies. Building on the recent success of data-driven approaches, we evaluate the combination of ion mobility-mass spectrometry (IMS-MS), density functional theory (DFT) featurization, and machine learning to predict and classify the binding modes of 1:1 complexes formed between cucurbit[6]uril (CB6) and diamine guests. Training a regression model with DFT-derived molecular descriptors and experimentally determined collisional cross sections (CCS) enables predicting the CCS of host-guest complexes with a diverse set of diamine guests. The predicted values naturally separate in two distinct groups corresponding respectively to inclusion and exclusion complexes, thereby enabling topology classification. This approach demonstrates that DFT-featurization and IMS-MS data capture well host-guest topology and provide a framework for the data-driven design of supramolecular assemblies.

Odontonema strictum (Acanthaceae) leave extract was investigated for its flavonoid content. Column chromatography was used for compound isolation and mass spectrometry was performed using electrospray ionization (ESI) in the negative ion mode for compound identification.The full characterization of luteolin 7-O-[β-D-apiofuranosyl-(1→2)-O-β-D-ribofuranoside], a flavone glycoside, was achieved using tandem mass spectrometry and high resolution 1D and 2D Nuclear Magnetic Resonance (NMR). Among the 10 flavonoids glycosides detected in the ethanol extract, beside the isolated one, 3 flavone glycosides with luteolin or apigenin aglycone were tentatively identified.

Justicia secunda Vahl (Acanthaceae) is a tropical herbaceous plant traditionally used by indigenous peoples of the Democratic Republic of the Congo (DRC) to treat symptoms associated with sickle cell disease (SCD), a genetic condition with life-threatening complications. Given the lack of side-effect-free drugs, alternative herbal therapies that can reduce or reverse red blood cell sickling may serve as safe and effective treatments. The primary objective of this study is to conduct a phytochemical screening of crude flavonoids extracted from J. secunda using LC-ESI/MS/MS. J. secunda extracts were evaluated for their phytoconstituents and anti-sickling properties. The anti-sickling properties were assessed through reverse sickling estimation, polymerization and oxidation inhibition, and osmotic fragility assays. Fractionation of the methanol extract and chemical profiling were performed by flash chromatography and high-performance thin-layer chromatography analysis respectively. Characterization and identification of the crude flavonoids were done using chromatography and spectroscopy methods. Chemical screening of crude flavonoids revealed the presence of 12 flavonoid O-glycosides based on one flavonol (methoxy-kaempferol) and two flavones (luteolin and apigenin). The crude flavonoid extracts demonstrated maximum reversal of sickled red blood cells (91.9 ± 0.8%), significant inhibition of hemoglobin polymerization (77.8 ± 7.6%) and hemoglobin S auto-oxidation (96.3 ± 0.2), and provided maximum protection of red blood cells against hyperhemolysis. The results validate the traditional use of J. secunda and identify potential compounds for the development of novel anti-sickling agents.