{"title":"Probing the Missing Links: Mass Spectrometry of Small-Molecule Clusters on the Pathway to Fibrils and Crystals","authors":"Thanh D. Do","doi":"10.1002/anse.202500241","DOIUrl":"10.1002/anse.202500241","url":null,"abstract":"<p>Small molecules such as amino acids (AAs) and metabolites are often treated as chemically simple species that either remain soluble or crystallize directly into ordered solids. Growing evidence challenges this view, revealing that many metabolites populate rich assembly landscapes containing oligomers and amyloid-like fibrils that bridge the gap between monomers and crystals. Far from being transient curiosities, these intermediate states can encode structural information that shapes toxicity, polymorph selection, catalysis, and disease progression. In this review, we explore how analytical mass spectrometry (MS), particularly ion mobility spectrometry–MS (IMS–MS) and MS-coupled ion spectroscopy, has opened a window onto these otherwise hidden assemblies. We show how IMS–MS resolves heterogeneous populations, captures early nucleation events, and exposes the decisive roles of charge balance, counterions, and additives in steering assembly pathways. Through representative examples spanning AAs and metabolites linked to amyloid formation and pathological crystallization, we argue that fibrillar intermediates can serve as deterministic waypoints rather than kinetic dead ends. We also confront the current limits of structural MS, from charge-induced bias to spectral congestion and modeling challenges, and highlight emerging solutions enabled by gentler ion handling, cryogenic spectroscopy, multidimensional IMS, and data-driven computation. Together, these advances transform MS from a passive observer into an active guide for discovering and predicting order in small-molecule assemblies.</p>","PeriodicalId":72192,"journal":{"name":"Analysis & sensing","volume":"6 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/anse.202500241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147568194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Probing the Missing Links: Mass Spectrometry of Small-Molecule Clusters on the Pathway to Fibrils and Crystals","authors":"Thanh D. Do","doi":"10.1002/anse.202500241","DOIUrl":"https://doi.org/10.1002/anse.202500241","url":null,"abstract":"<p>Small molecules such as amino acids (AAs) and metabolites are often treated as chemically simple species that either remain soluble or crystallize directly into ordered solids. Growing evidence challenges this view, revealing that many metabolites populate rich assembly landscapes containing oligomers and amyloid-like fibrils that bridge the gap between monomers and crystals. Far from being transient curiosities, these intermediate states can encode structural information that shapes toxicity, polymorph selection, catalysis, and disease progression. In this review, we explore how analytical mass spectrometry (MS), particularly ion mobility spectrometry–MS (IMS–MS) and MS-coupled ion spectroscopy, has opened a window onto these otherwise hidden assemblies. We show how IMS–MS resolves heterogeneous populations, captures early nucleation events, and exposes the decisive roles of charge balance, counterions, and additives in steering assembly pathways. Through representative examples spanning AAs and metabolites linked to amyloid formation and pathological crystallization, we argue that fibrillar intermediates can serve as deterministic waypoints rather than kinetic dead ends. We also confront the current limits of structural MS, from charge-induced bias to spectral congestion and modeling challenges, and highlight emerging solutions enabled by gentler ion handling, cryogenic spectroscopy, multidimensional IMS, and data-driven computation. Together, these advances transform MS from a passive observer into an active guide for discovering and predicting order in small-molecule assemblies.</p>","PeriodicalId":72192,"journal":{"name":"Analysis & sensing","volume":"6 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147567920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Self-Powered Potentiometric Sensing of Amoxicillin in Cow Milk and Waste Water Over Zinc Oxide Encapsulated Cellulose-Grafted Polyaniline","authors":"Chandra Shekhar Kushwaha, Vinay Kumar Singh, Nand Gopal Giri, Saroj Kr. Shukla","doi":"10.1002/anse.202500232","DOIUrl":"10.1002/anse.202500232","url":null,"abstract":"<p>A self-powered potentiometric sensing of residual amoxicillin (AMX) in milk, meat extract and waste water of hospital has been demonstrated over zinc oxide, cellulose and polyaniline (ZnO-en-Cell-g-PANI) nanocomposite. The chemical structure, morphology, and properties of nanocomposite was investigated by suitable analytical techniques and ASTM methods. The observed analytical results confirms the porous and heterogeneous structure of composite with axial oriented crystallinity, ∼3.28 × 10<sup>–4</sup> S cm<sup>–1</sup> electrical conductivity, and chemical responsive nature. Further, the 100 μm film of ZnO-en-Cell-g-PANI nanocomposite coated on ITO glass plate to use as an electrode for potentiometric sensing of residual AMX in waste water, meat extract and milk samples under optimum conditions and using own fabricated sensing set up. The experimental result revealed reproducibility, linear sensing range from 0.5 to 100.0 µM AMX concentrations, 2.24 mV µM<sup>−1</sup> cm<sup>−2</sup> sensitivity, 3.45 × 10<sup>−2 </sup>µM detection limit, 180 s response time, 20 s recovery time, 45 days stability at 7.0 pH and room temperature. The mechanism for non-enzymatic sensing of AMX has been proposed after correlating the induced potential and electrochemical surface interaction occurring between AMX molecules and ZnO-en-Cell-g-PANI.</p>","PeriodicalId":72192,"journal":{"name":"Analysis & sensing","volume":"6 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Self-Powered Potentiometric Sensing of Amoxicillin in Cow Milk and Waste Water Over Zinc Oxide Encapsulated Cellulose-Grafted Polyaniline","authors":"Chandra Shekhar Kushwaha, Vinay Kumar Singh, Nand Gopal Giri, Saroj Kr. Shukla","doi":"10.1002/anse.202500232","DOIUrl":"https://doi.org/10.1002/anse.202500232","url":null,"abstract":"<p>A self-powered potentiometric sensing of residual amoxicillin (AMX) in milk, meat extract and waste water of hospital has been demonstrated over zinc oxide, cellulose and polyaniline (ZnO-en-Cell-g-PANI) nanocomposite. The chemical structure, morphology, and properties of nanocomposite was investigated by suitable analytical techniques and ASTM methods. The observed analytical results confirms the porous and heterogeneous structure of composite with axial oriented crystallinity, ∼3.28 × 10<sup>–4</sup> S cm<sup>–1</sup> electrical conductivity, and chemical responsive nature. Further, the 100 μm film of ZnO-en-Cell-g-PANI nanocomposite coated on ITO glass plate to use as an electrode for potentiometric sensing of residual AMX in waste water, meat extract and milk samples under optimum conditions and using own fabricated sensing set up. The experimental result revealed reproducibility, linear sensing range from 0.5 to 100.0 µM AMX concentrations, 2.24 mV µM<sup>−1</sup> cm<sup>−2</sup> sensitivity, 3.45 × 10<sup>−2 </sup>µM detection limit, 180 s response time, 20 s recovery time, 45 days stability at 7.0 pH and room temperature. The mechanism for non-enzymatic sensing of AMX has been proposed after correlating the induced potential and electrochemical surface interaction occurring between AMX molecules and ZnO-en-Cell-g-PANI.</p>","PeriodicalId":72192,"journal":{"name":"Analysis & sensing","volume":"6 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Albumin-Assisted Supramolecular Probe for Ratiometric Detection of PFAS in Aqueous Medium","authors":"Supriya Joshi, Ritika Joshi, Abhay Vijay Kotkondawar, Manojkumar Jadhao","doi":"10.1002/anse.202500207","DOIUrl":"10.1002/anse.202500207","url":null,"abstract":"<p>Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants, and their growing concern requires the development of efficient detection methodologies. The present article introduces a novel supramolecular host–guest sensing system using human serum albumin (HSA) as the host and a specifically designed chromophoric azo dye, (E)-(2-hydroxy-5-((3,4,5-trimethoxyphenyl)diazenyl)phenyl)(pyrrolidine-1-yl)methanone (TPAZ), as the guest. The probe was used for ratiometric and colorimetric detection of PFOS, PFOA, and PFNA. Absorbance and fluorescence techniques were used to study the photophysical properties, binding stoichiometry, and site-specific interactions. The density functional theory calculations also supporting strong intramolecular charge transfer behavior and visible-light absorption. The TPAZ–HSA complex showed distinct spectral shifts and a visible color change from yellow to colorless upon interaction with PFAS, enabling rapid and selective detection, however, the sensor is selective toward PFAS as a class but not toward individual PFAS. This probe enables simple paper-based test strips for on-site PFAS detection in water using smartphhgone images. Molecular docking revealed the sensing mechanism and competitive binding of TPAZ and PFAS at albumin sites. This article demonstrates a simple, cost-effective, and selective sensing approach for on-site detection of PFAS in aqueous systems.</p>","PeriodicalId":72192,"journal":{"name":"Analysis & sensing","volume":"6 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Albumin-Assisted Supramolecular Probe for Ratiometric Detection of PFAS in Aqueous Medium","authors":"Supriya Joshi, Ritika Joshi, Abhay Vijay Kotkondawar, Manojkumar Jadhao","doi":"10.1002/anse.202500207","DOIUrl":"https://doi.org/10.1002/anse.202500207","url":null,"abstract":"<p>Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants, and their growing concern requires the development of efficient detection methodologies. The present article introduces a novel supramolecular host–guest sensing system using human serum albumin (HSA) as the host and a specifically designed chromophoric azo dye, (E)-(2-hydroxy-5-((3,4,5-trimethoxyphenyl)diazenyl)phenyl)(pyrrolidine-1-yl)methanone (TPAZ), as the guest. The probe was used for ratiometric and colorimetric detection of PFOS, PFOA, and PFNA. Absorbance and fluorescence techniques were used to study the photophysical properties, binding stoichiometry, and site-specific interactions. The density functional theory calculations also supporting strong intramolecular charge transfer behavior and visible-light absorption. The TPAZ–HSA complex showed distinct spectral shifts and a visible color change from yellow to colorless upon interaction with PFAS, enabling rapid and selective detection, however, the sensor is selective toward PFAS as a class but not toward individual PFAS. This probe enables simple paper-based test strips for on-site PFAS detection in water using smartphhgone images. Molecular docking revealed the sensing mechanism and competitive binding of TPAZ and PFAS at albumin sites. This article demonstrates a simple, cost-effective, and selective sensing approach for on-site detection of PFAS in aqueous systems.</p>","PeriodicalId":72192,"journal":{"name":"Analysis & sensing","volume":"6 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}