Patrick Romanens, Sofia Barluenga, Millicent Dockerill, Guixian Zhao, Francesco Russo, Nicolas Winssinger
{"title":"Peptides on Tap: Automated Flow Synthesis With Standard HPLC","authors":"Patrick Romanens, Sofia Barluenga, Millicent Dockerill, Guixian Zhao, Francesco Russo, Nicolas Winssinger","doi":"10.1002/hlca.70091","DOIUrl":"https://doi.org/10.1002/hlca.70091","url":null,"abstract":"<p>Peptide synthesis is central to biomedical research, yet automated flow synthesis typically requires custom-built instrumentation, limiting accessibility beyond specialized laboratories. Here we demonstrate that a standard analytical HPLC can be repurposed for fully automated flow-based peptide synthesis. By packing a short guard column with resin and programming reagent injections through the autosampler, we achieved efficient coupling and deprotection cycles under temperature-controlled flow, using TBEC/Oxyma activation. This setup exploits the precise flow control, heating, and in-line UV detection intrinsic to HPLC systems, enabling real-time monitoring of Fmoc deprotection. Using this approach, we synthesized peptides up to 30 residues, including GLP-1 and bivalirudin, with comparable yields and purity to conventional solid-phase synthesis. No significant epimerization was observed under optimized conditions, and crude bivalirudin displayed thrombin inhibition activity identical to purified reference material. The method was also used to obtain a 58-residue miniprotein in under 7 h on mg scale. This work introduces a simple, safe, and economical platform for automated peptide synthesis with the advent of high temperature flow accessible to any laboratory equipped with an HPLC.</p>","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":"109 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hlca.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sankar Jana, Emma Reig-Martí, Constanze Schultz, Michael Schmitt, Tobias Meyer-Zedler, S M Miftahul Islam, Iwan W. Schie, Ibane Abasolo, Miriam Royo, Juergen Popp
{"title":"In Vitro Raman Spectroscopic Characterization of Docetaxel-Loaded Polymeric Nanoparticles","authors":"Sankar Jana, Emma Reig-Martí, Constanze Schultz, Michael Schmitt, Tobias Meyer-Zedler, S M Miftahul Islam, Iwan W. Schie, Ibane Abasolo, Miriam Royo, Juergen Popp","doi":"10.1002/hlca.70088","DOIUrl":"https://doi.org/10.1002/hlca.70088","url":null,"abstract":"<p>Raman spectroscopy is widely used in drug development and delivery due to its label-free and non-destructive character. Reliable application to drug delivery systems requires unambiguous assignment of Raman bands from both the drug and the carrier material. Here, we establish the Raman spectral signatures of docetaxel (DTX)-loaded polymeric micelles (nanoparticles, NPs) based on Pluronic F-127, Soluplus, and a mixed Soluplus–TPGS system. DTX was nanoformulated to improve its aqueous solubility and therapeutic performance. In vitro FT-Raman measurements (1064 nm excitation) were performed on pure polymers, unloaded micelles, and DTX-loaded formulations. Detailed band assignments of the pure drug and nanocarriers were carried out and systematically compared with the loaded systems. Four characteristic DTX marker bands at 617, 1003, 1601, and 3072 cm<sup>−</sup><sup>1</sup> were clearly identified in Soluplus and Soluplus–TPGS nanoparticles, providing spectroscopic evidence of drug incorporation. Linear least-squares spectral decomposition enabled estimation of the relative Raman contributions of drug and carrier. The results demonstrate a higher loading capacity for Soluplus—TPGS mixed nanoparticles compared to pure Soluplus systems and establish a chemically rigorous Raman reference framework for future label-free studies of drug–polymer nanocarriers.</p>","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":"109 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hlca.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ana I. Benítez-Mateos","authors":"","doi":"10.1002/hlca.70090","DOIUrl":"https://doi.org/10.1002/hlca.70090","url":null,"abstract":"<p>A research group is successful, because of the teamwork. I would advise aspiring academics to pursue their passion and to be patient, “Rome wasn't built in a day”. My motto is “The best is yet to come…”, a reminder that more opportunities, discoveries, and accomplishments are still ahead of us. \u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":"109 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hlca.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seb Tyerman, Craig M. Robertson, David. J. Nelson, John A. Murphy
{"title":"Assessing the Role of Benzylic C─H Bonds in Suppressing Radical Chemistry Initiated by Benzynes","authors":"Seb Tyerman, Craig M. Robertson, David. J. Nelson, John A. Murphy","doi":"10.1002/hlca.70089","DOIUrl":"https://doi.org/10.1002/hlca.70089","url":null,"abstract":"<p>Reaction of KO<i>t</i>Bu with haloarenes in arene solvent leads to the formation of biaryls through radical intermediates, and we recently (2026) showed that the radical chemistry is initiated by the formation of benzynes. Our original studies (2014) compared the reactivity of iodobenzene and 2-iodo-<i>m</i>-xylene; the latter substrate cannot form <i>o</i>-benzynes. Whereas iodobenzene led to the formation of biaryls (40%), for 2-iodo-<i>m</i>-xylene this was suppressed almost to 0%. However, in the intervening time, we came to suspect that the iodoxylene was not an ideal substrate due to the potential reactivity of the Ar-Me groups both to base and to hydrogen atom abstraction reactions. We have now examined two new substrates where the Ar-Me groups are replaced by Ar-Ph groups. These substrates cause much more efficient initiation of radical chemistry, arising from the formation of <i>p</i>- and <i>m</i>- benzynes through the reaction of iodobenzenes with base. Importantly, these substrates allow assessment of the role of the Ar-Me groups in 2-iodo-<i>m</i>-xylene in suppressing radical chemistry.</p>","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":"109 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hlca.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Helvetica Chimica ActaPub Date : 2026-07-18Epub Date: 2026-06-18DOI: 10.1002/hlca.202500238
Robin Wisson, Elena Serino, Julien Foisnon, Lucile Lacourte, Véronique Guérin, Sophie Gonzalez, Véronique Eparvier, David Touboul
{"title":"Chemotaxonomic Classification of Annonaceae Species From Herbarium Samples Using LC-HRMS, Supported by Multivariate Curve Resolution Applied to Regions of Interest (ROIMCR)","authors":"Robin Wisson, Elena Serino, Julien Foisnon, Lucile Lacourte, Véronique Guérin, Sophie Gonzalez, Véronique Eparvier, David Touboul","doi":"10.1002/hlca.202500238","DOIUrl":"https://doi.org/10.1002/hlca.202500238","url":null,"abstract":"<div>\u0000 \u0000 <p>Chemotaxonomic approaches provide a valuable complement to morphological analysis and DNA barcoding techniques for classifying herbarium specimens, particularly in plant families where closely related species exhibit overlapping diagnostic traits. In this study, liquid chromatography–electrospray high-resolution mass spectrometry (LC–ESI–HRMS) data from 53 Annonaceae herbarium leaf samples were processed using the ROIMCR workflow, which integrates region-of-interest (ROI) filtering with multivariate curve resolution-alternating least squares (MCR-ALS). The resulting component areas were used to construct a hierarchical clustering that largely recovered species-level groupings, despite collection dates spanning more than two decades. This chemotaxonomic analysis corroborated most herbarium identifications, highlighted probable misassignments, and enabled the classification of previously unidentified specimens. Discriminant component analysis revealed that aporphine alkaloids and acetogenins constituted the principal chemical markers driving the separation of Annonaceae genera and species. The extension of the approach to bark and flower extracts showed that leaves and bark share many metabolites but differ markedly in relative abundances, which complicates building a unified, organ-independent classification. Overall, this work demonstrates that ROIMCR-based chemotaxonomy provides a robust LC–MS-compatible framework to exploit archived herbarium material and to strengthen species assignment in metabolite-rich plant families such as Annonaceae.</p>\u0000 </div>","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":"109 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148533453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maya Mischler, Kyrian Engel, Gabriel Di Lullo, Valentin Picard, Thibaud Rossel
{"title":"Selective Phosphate Fluorescence Detection Over Pyrophosphate in Aqueous Media With a Cerium-Based Chemosensor","authors":"Maya Mischler, Kyrian Engel, Gabriel Di Lullo, Valentin Picard, Thibaud Rossel","doi":"10.1002/hlca.70087","DOIUrl":"https://doi.org/10.1002/hlca.70087","url":null,"abstract":"<p>Phosphate ions are important molecules playing essential roles in biological and agricultural processes. Although numerous phosphate sensors have been reported, selective detection under physiological conditions and in complex media remains challenging. Over the past decades, several strategies have been developed to address this challenge, including the design of sophisticated receptors, but with limited success. Herein, using readily accessible chemicals, we report a straightforward metal extrusion-based fluorescence indicator displacement assay (MEFID) for the detection of phosphate. By combining a commercially available fluorophore and cerium ammonium nitrate (CAN), phosphate ions in aqueous solutions were successfully detected. We demonstrate that this inorganic complex detects phosphate ions at low micromolar concentrations, either spectrophotometrically or with the naked eye, with high selectivity over common competing anions including halides, acetates, carbonates, and remarkably, pyrophosphate. In addition, interference of the sensor with phosphorylated molecules appears to be minimal, thus providing a cost-effective and efficient chemosensor for phosphate over pyrophosphate.</p>","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":"109 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hlca.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148532743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ghewa AlSabeh, Algirdas Dučinskas, Jovana V. Milić, Michael Graetzel
{"title":"Mixed Ionic–Electronic Conduction in Layered Hybrid Halide Perovskites","authors":"Ghewa AlSabeh, Algirdas Dučinskas, Jovana V. Milić, Michael Graetzel","doi":"10.1002/hlca.70085","DOIUrl":"https://doi.org/10.1002/hlca.70085","url":null,"abstract":"<p>Mixed ionic–electronic conductivity of metal halide perovskites is a critical factor determining their application in optoelectronics, as well as the emerging field of optoionics. In particular, ionic migration in response to voltage bias and light contributes to the operational instability of halide perovskite materials and devices. A promising strategy to control ion migration is dimensional reduction, achieved by incorporating bulky organic cations between inorganic slabs to form two-dimensional or layered hybrid halide perovskites. In this perspective article, we discuss the mixed conductivity of layered halide perovskite materials and the impact on the operational stability of perovskite optoelectronics and emerging applications.</p>","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":"109 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hlca.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148533478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter Kluth, Constantin G. Daniliuc, Ulrich Hennecke
{"title":"Diastereoselective Synthesis of Amino Acid-Substituted 2,2’-Bipyrrolidines","authors":"Peter Kluth, Constantin G. Daniliuc, Ulrich Hennecke","doi":"10.1002/hlca.70084","DOIUrl":"https://doi.org/10.1002/hlca.70084","url":null,"abstract":"<div>\u0000 \u0000 <p>Bipyrrolidines are important chiral diamines with application in organocatalysis and the synthesis of ligands for transition metal complexes. Conventionally, these compounds are prepared by a photochemical dimerization of pyrrole, however, the method is not stereoselective, the isolation of stereopure products is tedious, and the method is difficult to apply to substituted bipyrrolidines. In this manuscript, it is shown that α-amino acid-substituted bipyrrolidines can be prepared in moderate to good yields by an intramolecular diamination reaction promoted by electrophilic iodinating agents. If amino acids with a sterically-demanding side chain such as valine or phenylalanine are used, high diastereoselectivities have been observed. The resulting <i>N</i>,<i>N</i>’-amino acid substituted bipyrrolidines could function after deprotection as tetradentate transition metal ligands.</p>\u0000 </div>","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":"109 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isomer Engineering of Phenazine and Tetraphenylethylene Derivatives for Enhanced Fluorescence in both Solid and Aggregation States","authors":"Jiaqin He, Yina Gu, Wenxiu Guo, Xun Chen, Junliang Liu, Genlin Wang, Shiyuan Zhou, Peiyang Gu","doi":"10.1002/hlca.70086","DOIUrl":"https://doi.org/10.1002/hlca.70086","url":null,"abstract":"<div>\u0000 \u0000 <p>Isomer engineering represents a strategy that preserves both the electron donor-acceptor connectivity and elemental composition of fluorescent molecules, while enables effective modulation of the electronic structure and holds potential for elucidating the influence of molecular architecture on fluorescence behavior. In this work, four new phenazine and tetraphenylethylene (TPE) derivatives were designed and synthesized through an isomer engineering strategy and a Suzuki-Miyaura coupling reaction. The TPE-based luminogens were introduced into the phenazine core at the 2,7- or 3,6-positions, resulting in the designation of the four compounds as 27TNE, 36TNE, 27TE, and 36TE, respectively. Among them, 27TNE and 36TNE exhibit characteristic aggregation-induced emission properties with high fluorescence quantum yields in the solid state (0.49 for 27TNE, 0.35 for 36TNE), whereas 27TE and 36TE show dual-state emission (DSE) with moderate fluorescence in both solution (0.74 for 27TE, and 0.64 for 36TE in dimethylformamide (DMF)) and solid states. The density functional theory calculations reveal the influence of different isomerization and central cores on the fluorescence behavior of these compounds.</p>\u0000 </div>","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":"109 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148532649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Helvetica Chimica ActaPub Date : 2026-07-18Epub Date: 2026-06-17DOI: 10.1002/hlca.202500237
Gianluca Bravetti, Aki Frankberg, Mahsa Shahsavan, Paul Zimmermann, Benjamin M. Gallant, Oleg Konovalov, Mohammad Reza Golobostanfard, Alexander Hinderhofer, Frank Schreiber, Dominik J. Kubicki, Jovana V. Milić
{"title":"Mechanosynthesis of Metal-Free Molecular Perovskites","authors":"Gianluca Bravetti, Aki Frankberg, Mahsa Shahsavan, Paul Zimmermann, Benjamin M. Gallant, Oleg Konovalov, Mohammad Reza Golobostanfard, Alexander Hinderhofer, Frank Schreiber, Dominik J. Kubicki, Jovana V. Milić","doi":"10.1002/hlca.202500237","DOIUrl":"https://doi.org/10.1002/hlca.202500237","url":null,"abstract":"<p>Metal-free halide perovskites have recently emerged as promising candidates for optoelectronic applications. However, their synthesis has largely depended on water-based single-crystal growth that limits material diversity, scalability, and practical implementation. Here, we present a mechanochemical route to synthesize <i>N,N</i>-diazabicyclo[2.2.2]octonium (H-DABCO)-based halide perovskites from the (DABCO)(NH<sub>4</sub>)X<sub>3</sub> (X = I, Br) compositions. The structural properties were confirmed by X-ray diffraction and solid-state nuclear magnetic resonance spectroscopy. Thin films were prepared from mechanosynthetic powders by spin-coating and characterized by in-situ grazing incidence wide-angle scattering measurements, as well as by UV–vis absorption and steady-state photoluminescence spectroscopy. This mechanosynthetic strategy provides a scalable, environmentally friendly pathway to broaden the scope of metal-free perovskites and advance their potential in sustainable optoelectronic technologies.</p>","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":"109 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hlca.202500237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148533753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}