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Chirality Unlocks Sub-Terahertz Molecular Dynamics in Peptide Nanotubes
Abstract Low-frequency modes in the picosecond range play a key role in molecular recognition and biomolecular function. Here, we investigate how these dynamics at the interfaces of self-assembled peptide biomaterials relate to fine structural details of the supramolecular assembly. We resolve terahertz and mid-infrared modes in individual diphenylalanine nanotubes by nanoscale microspectroscopy, uncovering a direct correlation between supramolecular chirality, molecular arrangement, and picosecond dynamics at the nanotube-environment boundary. By combining THz and mid-IR nanoscopy with a multiscale strategy spanning single nanotubes and ensemble measurements, supported by density functional theory calculations, we access the intrinsic picosecond response of peptide assemblies beyond the limits of conventional microscopy and ensemble averaging. Heterochiral (D-L) nanotubes display sharp resonances, whereas homochiral (L-L) nanotubes exhibit a comparatively featureless sub-THz profile, revealing a clear chirality-dependent contrast. Mode assignments show that the heterochiral features are dominated by localized torsional and bending motions of phenyl rings relative to the peptide backbone. Overall, chirality-dependent THz fingerprints emerge as sensitive descriptors of peptide nanotube architecture, while low-frequency nanospectroscopy provides a route to interrogate biomaterial interfaces under biologically relevant conditions. Autori Rajat Kumar, Erica Scarel, Andrea Perucchi, Lisa Vaccari, Prasanta Kumar Datta, Francesco D’amico, Paola Di Pietro, Silvia Marchesan, Federica Piccirilli Rivista ChemrXiv Data di pubblicazione 11/03/2026 Consulta la pubblicazione
A comprehensive framework for solution space exploration in community detection
Abstract: Community detection algorithms are essential tools for understanding complex networks, yet their results often vary between runs and are affected by node input order and the presence of outliers, undermining reproducibility and interpretation. This paper addresses these issues by introducing a framework for systematic exploration of the solution space, obtained through repeated runs of a given algorithm with permuted node orders. A Bayesian model assesses convergence, estimates solution probabilities, and provides a defensible stopping rule that balances accuracy and computational cost. Building on this process, we propose a taxonomy of solution spaces that offers clear diagnostics of partition reliability across algorithms and a shared vocabulary for interpretation. Applied to a real-world network, the approach shows that different algorithms produce various types of solution space, highlighting the importance of systematic exploration of the solutions before drawing scientific conclusions. Autori Fabio Morea, Domenico de Stefano Rivista Scientific Reports Data di pubblicazione 31/10/2025 Consulta la pubblicazione
Ultrafast Intermolecular Dynamics of Nanoconfined Water in Swollen Lipid Cubic Mesophases
Abstract Understanding the structure and dynamics of the hydrogen-bond network ofwater in topologically distinct swollen lipidic mesophases, is fundamental fortheir application in biomedical, pharmaceutical, and food science fields. Here,a positive and non-linear correlation between water hydrogen-bond dynamicsand interfacial water population is uncovered in inverse bicontinuous swollenmesophases across an extended temperature range (298–340 K). Particularly,small-angle X-ray scattering determines the mesophase’s structural features,uncovering a temperature-driven re-entrant phenomenon (reappearance) ofPn̄ 3m phase upon heating. This topologically rich environment, however, hasno detectable impact on the temperature dependence of the intermolecularmodes of water, as revealed by terahertz absorption spectroscopy. Specifically,these modes show distinct dynamics: the stretching mode exhibits longerlifetimes than the libration mode, yet with a higher temperature-dependence,with approximately two-fold lower Arrhenius activation energies. In contrast,both stretching and libration modes exhibit a monotonic decrease in lifetimewith increasing temperature, due to the increasing disruption of thehydrogen-bond network. Atomistic molecular dynamics simulations enablethe quantification of interfacial water population, which shows a positivecorrelation with intermolecular lifetimes in a nonlinear manner, revealing anon-additive coupling between interfacial water population and waterhydrogen-bond network dynamics within these systems. Autori Eva Zunzunegui-Bru, Serena Rosa Alfarano, Patrick Züblin, Laura Baraldi,Hendrik Vondracek, Federica Piccirilli, Lisa Vaccari, and Raffaele Mezzenga Rivista Small Data di pubblicazione 03/10/2025 Consulta la pubblicazione
Rational optimization of D3R/GSK-3β dual target-directed ligands as potential treatment for bipolar disorder: Design, synthesis, X-ray crystallography, molecular dynamics simulations, in vitro ADME, and in vivo pharmacokinetic studies
Abstract Bipolar disorder is a complex neuropsychiatric condition with a significant unmet medical need, as current treatments lack disease-modifying properties and multimodal therapeutic effects. To overcome the limitations of single-target drugs, we designed dual-target ligands that combine partial agonism at the dopamine D3 receptor (D3R) with inhibition of glycogen synthase kinase-3β (GSK-3β). We previously identified ARN24161 (1) as a promising prototype, demonstrating partial agonism at D3R (EC50 = 10.1 nM, % Eff. = 26.3) and GSK-3β inhibition (IC50 = 561 nM). However, its drug-like properties remained suboptimal. To optimize this compound, we initiated a multidisciplinary refinement campaign, leveraging computational modeling and crystallographic data to fine-tune the balance between D3R and GSK-3β activity, reduce P-glycoprotein (P-gp) affinity, and improve the pharmacokinetic profile. This effort led to the identification of ARN25297 (5), a moderately balanced dual-target ligand that exhibits partial agonism at D3R (EC50 = 13.1 nM, % Eff. = 17.1) and potent GSK-3β inhibition (IC50 = 47.0 nM). Notably, ARN25657 (16) emerged as the most well-balanced candidate, demonstrating enhanced D3R partial agonism (EC50 = 15.2 nM, % Eff. = 37.7) alongside strong GSK-3β inhibition (IC50 = 19.3 nM). Compound 16 also exhibited the lowest P-gp inhibition and significant improvements in in vitro ADME properties compared to prototype 1, while maintaining a balanced dual target profile. Although the PK profile of 16 remained comparable to that of prototype 1, these findings lay the groundwork for further lead optimization and structural refinement, driving future in vivo proof-of-concept toward innovative therapeutic strategies for bipolar disorder and related neuropsychiatric conditions. Autori RMC Di Martino, D Russo, I Penna, Andrea Dalle Vedove, R Spabnuolo, G Ottonello, M Summa, J Desantis, A Valeri, L Pruccoli, SK Tripathi, A Tarozzi, Paola Storici, S Girotto, R Bertorelli, A Armirotti, G Cruciani, T Bandiera, A Cavalli, G Bottegoni Rivista European Journal of Medicinal Chemistry Data di pubblicazione 25/06/2025 Consulta la pubblicazione
FL30: an epidermal growth factor kinase inhibitor overcoming T790M and C797S mutations through unique conformational modulation mechanism
Abstract Tyrosine kinase inhibitors (TKIs) targeting the oncogene Epidermal Growth Factor Receptor (EGFR) are widely used in the treatment of non-small cell lung cancer (NSCLC). In this context, the introduction of fourth-generation TKIs has significantly advanced targeted therapy for T790M and C797S EGFR mutations. Current therapeutic strategies are increasingly focusing on the design of orthoallosteric TKIs, which have shown promise in stabilizing the inactive conformation of mutated EGFR. In this context, we report the discovery of FL30, a small molecule with a flavone core that exhibits nanomolar potency against the EGFR-L858R/T790M mutation, even in the presence of the C797S mutation. The IC50 comparable to the Osimertinib – one of the most renowned EGFR-TKIs – emphasizes the remarkable success of the design approach. In NSCLC models, FL30 effectively inhibits cancer growth and EGFR phosphorylation selectively in cells with the EGFR mutations. Kinetic studies, molecular modeling, and Plasmon Internal Reflection Surface-Enhanced Infrared Absorption (PIR-SEIRA) microscopy suggests that FL30 binds to the orthosteric site while inducing the transition of the mutant EGFR toward an inactive-like state. These findings highlight FL30’s potential for further optimization and propose a novel approach for developing targeted therapies that combine orthosteric binding with allosteric modulation. Autori Elena Romagnoli, Emiliano Laudadio, Giovanna Mobbili, Leonardo Sorci, Giovanni Birarda, Federica Piccirilli, Lisa Vaccari, Hendrik Vondracek, Brenad Romaldi, Massimo Marcaccio, Paola Storici, Marta Semrau, Roberta Galeazzi, Andrea Toma, Vincenzo Aglieri, Pierluigi Stipa, Tatiana Armeni, Cristina Minnelli Rivista International Journal of Biological Macromolecules Data di pubblicazione 21/06/2025 Consulta la pubblicazione
Broadband terahertz signatures and vibrations of Phe–Phe peptide and its fibrils
Abstract In recent years, peptide-based nanomaterials have gained significant attention in drug discovery due to their biocompatibility and promising functionality in biophysical processes. This current study employs terahertz (THz) spectroscopy and density functional theory (DFT) to investigate the vibrational properties of the phenylalanine dipeptide (Phe–Phe), a building block with notable self-assembling properties and potential applications in drug delivery and nanostructured biomaterials. The dynamics of proteins and biomolecules occurring on the picosecond timescale can be probed by THz spectroscopy and is closely related to their functionality. Here, we investigate the low-frequency vibrational modes of Phe–Phe under two different conditions, as crystalline commercial powder and post-self-assembled powder, in the 0.2–4 THz range. The refractive index of pure Phe–Phe, as evaluated from THz spectroscopy, is approximately 1.47, and the THz absorption peaks are observed at 0.55, 0.83, 1.13, 1.40, 1.68, 2.18, 2.71, 3.00, and 3.33 THz. Potential energy distribution (PED) analysis provides a detailed assignment of the observed modes and identifies characteristic vibrational features. The novel thin bi-layer approach for sample preparation employed here proved to be effective in terms of signal-to-noise ratio and in eliminating artifacts possibly originating from the host material. This combined experimental–computational approach not only offers valuable insights into the conformational flexibility and self-assembly potential of Phe–Phe, but also underscores the efficacy of THz spectroscopy and DFT analysis for studying the vibrational properties of peptides, with implications for biophysics, nanotechnology, and biochemistry. Moreover, this study highlights the impact of intermolecular interactions on the vibrational spectra by comparing crystalline powder and self-assembled peptide powder. Autori Rajat Kumar, Federica Piccirilli, Paola Di Pietro, Johannes Schmidt, Giovanni Birarda, Lisa Vaccari, Andrea Perucchi, Prasanta Kumar Datta Rivista Analyst Data di pubblicazione 24/04/2025 Consulta la pubblicazione
Eco-friendly NaCl glycerol-based deep eutectic electrolyte for high-voltage electrochemical double layer capacitor
Abstract Herein, we propose eco-friendly electrolytes based on sodium chloride as a hydrogen bond acceptor and glycerol as a hydrogen bond donor, as alternatives to toxic, flammable and unsustainable electrolytes commonly used in electrochemical energy storage systems. By means of an in-depth multi-technique investigation, including Raman and FT-FIR spectroscopy, of the formulated electrolytes, we point out the effect of the structuring of the system on the transport and electrochemical properties. The 1 : 10 molar ratio mixture proves to be a deep eutectic solvent (DES), showing good room temperature ionic conductivity (0.186 mS cm−1) and electrochemical stability (≈3 V). When implemented as electrolyte in an activated-carbon electrochemical double layer capacitor, this DES exhibits superior performance compared to mixtures with different molar ratio and those containing ethylene glycol as the hydrogen bond donor, with a high operational voltage (2.6 V), a specific capacitance of 14.1 F g−1, and a remarkable cycling stability. These findings highlight the potential of glycerol-based DESs as alternative electrolytes for sustainable electrochemical energy storage applications. Autori Daniele Motta, Alessandro Damin, Hamideh Darjazi, Stefano Nejrotti, Federica Piccirilli, Giovanni Birarda, Claudia Barolo, Claudio Gerbaldi, Giuseppe Antonio Elia, Matteo Bonomo Rivista Green Chemistry Data di pubblicazione 31/03/2025 Consulta la pubblicazione
Cobalt recycling patents dataset selected using ‘green’ classification codes: Focus on the nickel manganese cobalt (NMC) batteries recycling
Abstract Il Critical Raw Materials Act è stato emanato per affrontare i rischi percepiti riguardanti le catene di approvvigionamento di materie prime critiche alla luce della crescita prevista della domanda. Il cobalto è una delle materie prime critiche per l’UE: svolge un ruolo centrale nella transizione verso un’economia a basse emissioni di carbonio ed è cruciale per le batterie che alimentano i veicoli elettrici. L’industria del cobalto è importante non solo per la transizione verde, ma anche perché crea opportunità di lavoro, dato che l’Europa è la terza regione più vasta nella catena del valore globale del cobalto. Il mercato globale dei veicoli elettrici a batteria (BEV) è in continuo aumento, il che comporta una consistente domanda di materiali per la produzione di batterie agli ioni di litio (LIB). In particolare, le batterie al litio nichel manganese cobalto (NMC) sono uno dei tipi di batterie principali utilizzati nei BEV e il riciclo dei materiali dalle batterie usate per produrre nuove batterie può mitigare il rischio di approvvigionamento di materiali. Il presente studio concerne la creazione e il confronto di due dataset di brevetti riguardanti il riciclo del cobalto, rispettivamente ottenuti senza (dataset 1) e con (dataset 2) l’aggiunta di un codice di classificazione CPC specifico ‘verde’ ad una vasta lista di codici di classificazione riguardanti il riciclo dei materiali. In particolare, il CPC Y02P10/20 determina un miglioramento significativo dell’esaustività della ricerca riguardante il riciclaggio del cobalto nel dataset 2, d’altra parte potrebbe anche generare problemi evidenziati da una successiva selezione di quei risultati che in linea di principio sono focalizzati sul recupero delle batterie NMC ma caratterizzati da diversi falsi positivi. Pertanto, si raccomanda una strategia di affinamento per rendere l’accuratezza del dataset NMC comparabile a quella che caratterizza i risultati NMC del dataset 1 ottenuti senza applicare alcun criterio di affinamento. Author Riccardo Priore Journal Data in Brief, March 2024, 105519 Date Available online 13/03/2024 Consult the paper
A supported lipid bilayer to model solid-ordered membrane domains
Abstract Membrane models are widely used to mimic the behaviour of native plasma membranes and to simulate interactions occurring at their interface. Such models can be built up with different molecular compositions, ranging from single phospholipids to more complex, heterogeneous mixtures of phospho- and sphingo-lipids, possibly enriched with cholesterol and proteins. In particular, mixing different lipids and cholesterol is instrumental to promote the formation of phase-separated, ordered domains, which resemble the structure of lipid rafts, specialized functional domains of real membranes. According to the specific lipid composition, physical characteristics of the rafts can be tuned, such as fluidity, strongly related to membrane biological activity. Here, we introduce a novel three-component membrane model constituted by the mixing of a saturated phospholipid, 1,2-dimyristoyl-sn–glycero-3-phosphocholine (DMPC), sphingomyelin and cholesterol to mimic the presence of solid ordered rafts and to study their behaviour. Differential scanning calorimetry, neutron reflectometry, and atomic force microscopy were synergistically applied to gain information on the membrane’s transverse and lateral organization, as well as on its thermotropic behaviour. The membrane model benefits from the use of DMPC, a lipid (i) characterized by an accessible transition temperature; (ii) saturated; (iii) fluid at physiological temperature and (iv) commercially available in both protiated and deuterated forms. The proposed model, along with the wide range of biophysical techniques employed, constitutes an ideal system to study the molecular mechanisms and the physical properties that govern membrane functions, such as molecular signalling and membrane trafficking. Autori Sally Helmy, Paola Brocca, Alexandros Koutsioubas, Stephen C.L. Hall, Luca Puricelli, Pietro Parisse, Loredana Casalis, Valeria Rondelli Rivista Journal of Colloid and Interface Science Data di pubblicazione 14/03/2025 Consulta la pubblicazione
Co-assembled supramolecular hydrogels: nano-IR sheds light on tripeptide assemblies
Abstract Supramolecular hydrogels composed of self-assembling short peptides are gaining momentum for enzyme mimicry. In particular, multicomponent systems that feature similar peptides with a self-assembling motif (e.g., Phe–Phe) and catalytic residues (e.g., His, Asp) offer a convenient approach to organize in space, functional residues that typically occur at enzymatic active sites. However, characterisation of these systems, and especially understanding whether the different peptides co-assemble or self-sort, is not trivial. In this work, we study two-component hydrogels composed of similar tripeptides and describe how nano-IR can reveal important details of their packing, thus demonstrating it to be a useful technique to characterise multicomponent, nanostructured gels. Autori Paola Alletto, Ana M. Garcia, Federica Piccirilli, Silvia Marchesan Rivista Faraday Discussions Data di pubblicazione 21/02/2025 Consulta la pubblicazione
CO2 and Temperature Induced Switching of a Flexible Metal–Organic Framework with Surface-Mounted Nanoparticles
Abstract Within the material family of metal–organic frameworks (MOFs) the subclass of flexible MOFs (flexMOFs) has attracted great attention, showing structural flexibility as a response to external stimuli such as guest adsorption, temperature, and pressure. Hybrid composites like nanoparticle (NP) loaded flexible MOFs, which stand to potentially combine advantageous properties of both are yet largely unexplored. Here the synthesis of flexMOFs with surface mounted nanoparticles, e. g. NP@Zn2(BME-bdc)2dabco composites (NP = Pt and SiO2 nanoparticles, BME-bdc2− = 2,5-bismethoxyethoxy-1,4-benzenedicarboxylate, dabco = 1,4-diazabicyclo[2.2.2]octane) is reported, studying the impact of nanoparticles on the stimulus-responsiveness of a flexMOF. It is shown that CO2 physisorption triggered flexibility of the MOF is retained and reversible for all NP@flexMOF composites. Additionally, it is observed that NPs stabilize the large pore state of the MOF, slightly increasing and shifting the switching pressure window. This effect is also observed during temperature-induced switching but Pt@flexMOF composites partially lose long-range order during the reversion to their narrow pore state, while attached SiO2 NPs allow for a fully reversible transition. These findings suggest that the total exerted material strain triggering the switching is heavily dependent on NP size and the applied stimulus and that guest-induced switchability can be fully realized in NP@flexMOF hybrid materials. Autori Jan Berger, Stephanie Terruzzi, Hana Bunzen, Filippo Ballerini, Marco Vandone, Marcello Marelli, Luca Braglia, Roland A. Fischer, Valentina Colombo, Gregor Kieslich Rivista Small Data di pubblicazione 07/01/2025 Consulta la pubblicazione
Innovation in rare earths recycling: A quantitative and qualitative analysis of patent data
Abstract Gli elementi delle terre rare (REE) sono essenziali per la transizione digitale e la decarbonizzazione. Tuttavia, la loro filiera è altamente concentrata e la loro estrazione ha un elevato impatto ambientale. Le soluzioni di economia circolare potrebbero fornire un doppio vantaggio: ridurre il rischio di fornitura per i paesi dipendenti dalle importazioni e mitigare gli impatti dell’estrazione di REE. Questo articolo si concentra sul riciclo di REE e fornisce una panoramica globale completa delle dinamiche di innovazione in questo settore utilizzando i dati sui brevetti. La metodologia di ricerca proposta per identificare i brevetti di riciclo dei REE si articola in due fasi: l’utilizzo della classificazione ENV-TECH dell’OCSE per le tecnologie verdi e l’occorrenza di parole chiave. È stata sviluppata una serie di metriche quantitative e qualitative per esplorare le dinamiche di innovazione a livello di Paese, richiedente e per tipo di tecnologia. La Cina emerge chiaramente come il mercato più attraente per i brevetti di riciclo di REE e le università cinesi sono le richiedenti più attive a livello mondiale. Al contrario, le domande di brevetto in tutti gli altri Paesi hanno mostrato tendenze stagnanti nell’ultimo decennio. In particolare, l’Europa ha un numero inferiore sia di domande di brevetto che di brevetti sviluppati rispetto agli Stati Uniti e al Giappone. Tuttavia, gli indicatori di qualità dei brevetti mostrano un quadro molto diverso: i richiedenti statunitensi e giapponesi sembrano essere all’avanguardia tecnologica in quanto ricevono più citazioni e sono più orientati a proteggere le loro invenzioni a livello internazionale. La nostra analisi evidenzia quindi l’importanza di considerare sia le metriche quantitative che qualitative dei brevetti quando si esaminano le tendenze dell’innovazione nel riciclo delle terre rare. Per finire, nell’articolo si discutono i determinanti di questi fenomeni osservati, si forniscono indicazioni di policy, in particolare per i paesi dipendenti dalle importazioni di terre rare, e si propongono percorsi per la ricerca futura nell’intersezione tra materiali critici (come le terre rare), l’economia circolare e gli studi sull’innovazione. Autori Riccardo Priore , Marco Compagnoni , Marinella Favot Rivista Resources Policy Volume 102, March 2025, 105519 Data di pubblicazione Disponibile dal 24/02/2025 Consulta la pubblicazione