Analytical chemistry articles within Nature Chemistry

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  • Article
    | Open Access

    Evolution separates complex modern enzymes from their hypothetical simpler early ancestors, which raises the question of how unevolved sequences can develop new functions. Here a library of non-natural protein sequences was subjected to ultrahigh-throughput screens in microfluidic droplets, leading to the isolation of a phosphodiesterase enzyme capable of hydrolysing the biological second messenger, cyclic AMP.

    • J. David Schnettler
    • , Michael S. Wang
    •  & Michael H. Hecht

  • News & Views |

    X-ray diffraction analysis typically affords the static 3D structures of given compounds or materials, but to understand chemical processes, the visualization of fast structural changes is desirable. Time-resolved femtosecond crystallography has now been used to monitor the structural dynamics of a photoactive metal–organic framework.

    • Lauren E. Hatcher
    •  & Paul R. Raithby

  • Article
    | Open Access

    Time-resolved femtosecond crystallography (TR-SFX) is a powerful technique to monitor structural transitions in protein crystals at the atomic level, but its use in non-protein synthetic materials remains limited. Now TR-SFX has been used to visualize the structural dynamics of metal–organic frameworks, showing the potential of this tool to study the dynamic motion of crystalline porous materials.

    • Jaedong Kang
    • , Yunbeom Lee
    •  & Hyotcherl Ihee

  • Research Briefing |

    We developed a high-throughput, unbiased strategy for the identification of endogenous biomolecular condensates by merging cell volume compression, sucrose density gradient centrifugation and quantitative mass spectrometry. We demonstrated the performance of this strategy by identifying both global condensate proteins and those responding to specific biological processes on a proteome-wide scale.

  • Article |

    High-throughput proteome-wide methods for identifying endogenous proteins that phase separate or partition into condensates during certain physiological events are needed but remain a challenge. Now, a high-throughput, unbiased and quantitative strategy can identify endogenous biomolecular condensates and screen proteins involved in phase separation on a proteome-wide scale.

    • Pengjie Li
    • , Peng Chen
    •  & Yiwei Li

  • Review Article |

    Nanopore label-free sequencing of DNA and RNA at the single-molecule level offers rapid readout, high accuracy, low cost and portability. This Review surveys technologies underpinning commercial and academic nanopore sequencing, and examines how underlying biochemical advances can fuel future developments in nanopore-based protein sequencing.

    • Adam Dorey
    •  & Stefan Howorka

  • Article |

    Lipidomics aims to uncover lipid functions in biological systems and disease. Quantifying lipids is challenging due to highly diverse chemical structures. Here a diazobutanone-assisted isobaric labelling method is developed that relies on diazobutanone and isobaric mass tags to target phosphate- and sulfate-containing lipids, enabling multiplexed lipidomic quantification in complex mixtures.

    • Ting-Jia Gu
    • , Peng-Kai Liu
    •  & Lingjun Li

  • News & Views |

    Cryptic halogenation reactions result in natural products with diverse structural motifs and bioactivities. However, these halogenated species are difficult to detect with current analytical methods because the final products are often not halogenated. An approach to identify products of cryptic halogenation using halide depletion has now been discovered, opening up space for more effective natural product discovery.

    • Ludek Sehnal
    • , Libera Lo Presti
    •  & Nadine Ziemert

  • News & Views |

    As the need for specific fluorescent probes that enable high sensitivity and super-resolution imaging experiments continues to grow, it is imperative to develop new, well-characterized methods to modulate the emission of fluorophores. Now, a general platform affords visible-to-NIR fluorogenic fluorophores by engineering a simple cyclization event into cyanine dyes.

    • Quintashia D. Wilson
    •  & Ellen M. Sletten

  • Article |

    Sequences of synthetic polymers are generally heterogeneous and dictate many of their physiochemical properties, but are challenging to determine. Now an imaging method, termed CREATS (coupled reaction approach toward super-resolution imaging), can count, localize and identify each monomer of single polymer chains during (co)polymerization.

    • Rong Ye
    • , Xiangcheng Sun
    •  & Peng Chen

  • Article |

    Detecting genetic mutations, such as single nucleotide polymorphisms (SNPs), is essential for disease diagnostics but can be difficult using homomultivalent DNA hybridization-based approaches. Now, heteromultivalent hybridization is used to fine-tune binding specificity for the detection of one or two SNPs in a single target, enabling straightforward discrimination between adjacent and distant mutations and different viral strains.

    • Brendan R. Deal
    • , Rong Ma
    •  & Khalid Salaita

  • News & Views |

    Although light-driven conversion of carbon dioxide receives widespread attention, it is also criticized due to the challenge of discerning true product formation from that of impurities. Now, significantly advanced guidelines for proper product identification have been developed, so we can better trust in what we see.

    • Jennifer Strunk

  • Article
    | Open Access

    Inspired by the design of peptide and nucleic acid sequences to adopt particular three-dimensional shapes, natural glycan motifs have now been combined to construct a glycan that adopts a hairpin conformation in water. Thus a designed glycan can now autonomously fold into a stable secondary structure absent in nature.

    • Giulio Fittolani
    • , Theodore Tyrikos-Ergas
    •  & Martina Delbianco

  • Article |

    Stabilization of RNAs for storage, transport and biological application remains a profound challenge. Now, it has been shown that reversible 2′-OH acylation with easily accessible acylimidazoles unlocks efficient protection of RNA. RNA can be deprotected by non-basic nucleophiles or spontaneously in cells to restore RNA functions.

    • Linglan Fang
    • , Lu Xiao
    •  & Eric T. Kool

  • Perspective |

    Bioresponsive hyperpolarized probes contain magnetic resonance signals that can be many orders of magnitude larger than those of common, thermally polarized probes. This Perspective discusses how bioresponsive hyperpolarized probes can be directly linked to biological events to give functional information, enabling the mapping of physiological processes and diseases in real time using magnetic resonance.

    • Goran Angelovski
    • , Ben J. Tickner
    •  & Gaoji Wang

  • Article
    | Open Access

    Continuous-rotation 3D electron diffraction is a powerful technique to determine structures from nanocrystals. A data treatment method that takes into account dynamical diffraction effects has now been shown to lead to more accurate structure models, better sensitivity to weak signals and a reliable determination of absolute configuration—even for materials containing only light atoms.

    • Paul B. Klar
    • , Yaşar Krysiak
    •  & Lukas Palatinus

  • Article |

    Crystals of hexachlorobenzene have now been shown to support the autonomous motion of water and particulate matter over their surface. Parallel microchannels present at the surface of the crystal gradually widen by sublimation, propelling droplets of condensed ambient water that can also transport microscopic amounts of material such as silver microparticles.

    • Patrick Commins
    • , Marieh B. Al-Handawi
    •  & Panče Naumov

  • Research Briefing |

    Serial rotation electron diffraction (SerialRED) enables rapid and reliable phase analysis and structure determination of complex polycrystalline materials that cannot be routinely characterized using X-ray diffraction. Five zeolite phases were identified in a single synthesis product by automated screening of hundreds of crystals, demonstrating the power of SerialRED for materials development.

  • Article |

    A nanopore framework has been developed to reveal the crosstalk effect on the renin–angiotensin system. By reading the single-amino-acid differences in angiotensin peptides with high accuracy and high efficiency, the selective inhibition of angiotensin-converting enzyme by angiotensin-converting enzyme 2 was revealed. This activity was shown to be suppressed by the spike protein of SARS-CoV-2.

    • Jie Jiang
    • , Meng-Yin Li
    •  & Yi-Tao Long

  • Article
    | Open Access

    X-ray diffraction is crucial for the phase elucidation of polycrystalline materials but remains challenging for complex multiphase systems. Now serial rotation electron diffraction has been shown to enable rapid, reliable and semiquantitative phase analysis of such systems, facilitating high-throughput screening of complex synthesis systems and providing new opportunities for materials development.

    • Yi Luo
    • , Bin Wang
    •  & Xiaodong Zou

  • Article
    | Open Access

    Native mass spectrometry has been used to interrogate both biased signalling and allosteric modulation of the β1-adrenergic receptor. Simultaneously capturing the effects of ligand binding and receptor coupling to different G proteins has enabled the relative importance of specific interactions to be investigated.

    • Hsin-Yung Yen
    • , Idlir Liko
    •  & Carol V. Robinson

  • Thesis |

    Sit back and settle in for a tour of the chemical analysis instruments aboard the James Webb Space Telescope and the techniques being used to explore the planets beyond our Solar System.

    • Bruce C. Gibb

  • Article
    | Open Access

    Proteins rich in phenylalanine-glycine (FG) repeats can phase separate through FG–FG interactions. The molecular interactions of an important FG-repeat protein, nucleoporin 98, have now been studied in liquid-like transient and amyloid-like cohesive states. These interactions underlie the behaviour of FG-repeat proteins and their function in physiological and pathological cell activities.

    • Alain Ibáñez de Opakua
    • , James A. Geraets
    •  & Markus Zweckstetter

  • Article |

    A method has been developed to identify RNA transcript isoforms at the single-molecule level using solid-state nanopore microscopy. In this method, target RNA is refolded into RNA identifiers with designed sets of complementary DNA strands. Each reshaped molecule carries a unique sequence of structural (pseudo)colours that enables identification and quantification using solid-state nanopore microscopy.

    • Filip Bošković
    •  & Ulrich Felix Keyser

  • Perspective |

    Droplet interface bilayers (DIBs) are a type of artificial bilayer that can act as cell membrane mimics. This Perspective surveys how DIBs can be used to mimic key cellular features (such as bilayer asymmetry) and processes (such as drug movement), and discusses challenges that need to be overcome to enable DIBs to reach their full potential as biomimetic model membranes.

    • Elanna B. Stephenson
    • , Jaime L. Korner
    •  & Katherine S. Elvira

  • Article |

    The composition of toxic protein aggregates associated with neurodegenerative diseases is difficult to determine. Now, a method has been developed that can capture amyloid-containing aggregates in human biofluids using a structure-specific chemical dimer. This method—known as amyloid precipitation—enables unbiased determination of the molecular composition and structural features of the in vivo aggregates.

    • M. Rodrigues
    • , P. Bhattacharjee
    •  & D. Klenerman

  • Article |

    The process by which life arose using information from the prebiotic environment and inherent molecular reactivity is unclear. Now, it has been shown that systems of chemical reactions exhibit well-defined self-organization in varying environments, providing a potential mechanism for chemical evolution processes that bridge the gap between prebiotic building blocks and life’s origin.

    • William E. Robinson
    • , Elena Daines
    •  & Wilhelm T. S. Huck

  • Article |

    Despite much research, the high-spin-state relaxation mechanism of Fe(II) spin-crossover complexes is unresolved. Using ultrafast circular dichroism spectroscopy it has now been revealed that the spin relaxation is driven by a torsional twisting mode, which breaks the chiral symmetry of a prototypical Fe(II) compound. Stereocontrolling the configuration of the complex can thus be used to slow down the spin relaxation.

    • Malte Oppermann
    • , Francesco Zinna
    •  & Majed Chergui

  • Q&A |

    In 2017 Professor Frances S. Ligler was inducted into the National Inventors Hall of Fame for her inventions in portable optical biosensors. Professor Ligler now talks to Nature Chemistry about the challenge of developing new sensor designs into reliable products, and some of the pitfalls to avoid in the development process.

    • Russell Johnson

  • News & Views |

    Extending mass spectrometry measurements of biomolecules into the megadalton regime is challenging due to the limited resolving power of currently used mass analysers. Now, using single ion-charge detection Orbitrap mass spectrometry, a mass accuracy of 0.001% has been demonstrated for protein particles larger than 9 MDa.

    • Muhammad A. Zenaidee
    •  & Joseph A. Loo

  • Article |

    Catalytic transformations of methane frequently involve the formation of a metal–methane complex, but these compounds are challenging to observe. Now, a relatively long-lived osmium–methane complex has been characterized using NMR spectroscopy and forms from the direct binding of methane to a photolytically generated, coordinatively unsaturated cationic osmium–carbonyl complex dissolved in an inert hydrofluorocarbon solvent at –90 °C.

    • James. D. Watson
    • , Leslie. D. Field
    •  & Graham. E. Ball

  • Article |

    Self-propelled artificial chemical swimmers have previously been developed for chemical sensing. Now, hybrid bioelectrochemical swimmers, capable of translating chiral molecular information into macroscopic motion, have been developed. Diastereomeric interactions between enantiopure oligomers immobilized on the swimmer and a chiral molecule present in solution control the trajectory of the device.

    • Serena Arnaboldi
    • , Gerardo Salinas
    •  & Alexander Kuhn

  • Article |

    Methods to detect and identify bacteria typically rely on enrichment steps such as bacterial culture and nucleic acid amplification. Now, an assay for detecting bacteria based on a two-channel electrical chip that combines electroactive DNAzymes with an electrochemical readout, has been developed. This assay enables reagentless and culture-free detection of bacteria in clinical samples.

    • Richa Pandey
    • , Dingran Chang
    •  & Leyla Soleymani

  • Article |

    Droplet interface bilayer measurements have now shown that membranes formed from chiral phospholipid bilayers are enantioselectively permeable to chiral amino acids. The results show that membrane stereochemistry is necessary and sufficient to drive such enantioselective transport, presenting a new potential route to homochirality. These findings could also have implications for pharmacokinetics and drug design.

    • Juan Hu
    • , Wesley G. Cochrane
    •  & Brian M. Paegel

  • Article |

    DNA G-quadruplexes can adopt a variety of secondary structures, but it is challenging to identify and classify them quickly. Multivariate analysis of different fluorescence enhancements—generated from an arrayed suite of synthetic hosts and cationic dyes—enables discrimination between G-quadruplex structures of identical length and similar topological types.

    • Junyi Chen
    • , Briana L. Hickey
    •  & Wenwan Zhong

  • Article |

    A reagentless method for detecting analytes based on the motion of an inverted molecular pendulum has now been developed. The sensor is capable of detecting important physiological markers of stress, allergy, cardiovascular health, inflammation and cancer and works in blood, saliva, urine, tears and sweat. The sensor is also capable of collecting data in living animals.

    • Jagotamoy Das
    • , Surath Gomis
    •  & Shana O. Kelley

  • Meeting Report |

    The confined geometry of nanopores enables a wealth of chemistry and analysis to be conducted at the single-molecule scale. Yi-Lun Ying, Aleksandar P. Ivanov and Vincent Tabard-Cossa report on recent developments discussed at the 2020 Nanopore Electrochemistry Meeting.

    • Yi-Lun Ying
    • , Aleksandar P. Ivanov
    •  & Vincent Tabard-Cossa

  • Article |

    A method for the covalent labelling of proteins by installing a biostable peptide nucleic acid (PNA) tag has now been developed. The PNA label serves as a generic landing platform that enables the recruitment of fluorescent dyes via nucleic acid hybridization and fluorophore removal by toehold-mediated strand displacement. Imaging of cell surface receptors, including internalized receptors, has been demonstrated using this approach.

    • Georgina C. Gavins
    • , Katharina Gröger
    •  & Oliver Seitz

  • Q&A |

    Yujia Qing, an early-career researcher at the University of Oxford, talks to Nature Chemistry about winning the Dream Chemistry Award 2019, her chemistry dream of ‘Sequencing Life’, and the challenge this represents.

    • Russell Johnson

  • News & Views |

    The tumour microenvironment has a specific enzymatic fingerprint, which provides opportunities for cancer therapy. Now, two studies show how this unique chemical environment can be used to produce reporter molecules or nanoclusters within the tumour that can subsequently be identified in urine or breath, enabling cancer detection and monitoring.

    • Alexander N. Zelikin

  • News & Views |

    Synthetic genetic circuits leverage the information processing capability of biological machinery to tackle complex sensing tasks, yet they lack many of the advantages inherent to electrical computation. Now, an interface has been designed that provides an electrical output for synthetic genetic circuits.

    • Robbyn K. Anand
    •  & Kira L. Rahn

  • Article |

    It is difficult to develop suitable fluorescent probes for live-cell nanoscopy, but a general strategy is now reported that can transform regular fluorophores into fluorogenic probes with excellent cell permeability and low unspecific background signals. Using this approach, probes in a variety of colours were developed for different cellular targets and used for wash-free, multicolour, live-cell confocal and STED microscopy.

    • Lu Wang
    • , Mai Tran
    •  & Kai Johnsson

  • Article |

    Gene-circuit-based sensors have, to date, largely relied on optical proteins (such as green fluorescent protein) to report the output, which limits the signalling bandwidth. Now, an electrochemical output has been developed and integrated with cell-free gene circuits. This approach enables multiplexing of sensors and introduces the possibility of electronic-based logic, memory and response elements to synthetic biology.

    • Peivand Sadat Mousavi
    • , Sarah J. Smith
    •  & Keith Pardee

  • Review Article |

    ortho-Aminomethylphenylboronic acids are routinely used in sensors for carbohydrates, but the function of the o-aminomethyl group in enhancing binding affinity and modulating the emission of appended fluorophores has been the matter of some debate. This Review presents a unified picture of the structural features, mechanisms of sugar complexation and photophysics of these kinds of sensors.

    • Xiaolong Sun
    • , Brette M. Chapin
    •  & Eric V. Anslyn

  • Article |

    Gas sorption studies in porous materials typically reflect their overall gas uptake. Now, using a ‘gas adsorption crystallography’ method, the gas adsorption isotherms of two metal–organic frameworks (MOFs) have been quantitatively decomposed into sub-isotherms that reflect the pore-filling behaviour of various guests in the different types of pores present in the MOFs.

    • Hae Sung Cho
    • , Jingjing Yang
    •  & Osamu Terasaki

  • Article |

    I-motif DNA structures are thought to form in cytosine-rich regions of the genome and to have regulatory functions; however, in vivo evidence for the existence of such structures has so far remained elusive. Now an engineered antibody that is selective for i-motif structures has been developed and used to detect i-motifs in the nuclei of human cells.

    • Mahdi Zeraati
    • , David B. Langley
    •  & Daniel Christ

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