Yangjie Li

All Publications

• Fragment Correlation Mass Spectrometry Enables Direct Characterization of Disulfide Bond Cleavage Pathways of Therapeutic Peptides. Analytical chemistry Li, Y., Cavet, G., Zare, R. N., Driver, T. 2024

  Abstract

  Therapeutic peptides that are connected by disulfide bonds are often difficult to analyze by traditional tandem mass spectrometry without chemical modification. Using fragment correlation mass spectrometry, we analyzed 56 pairs of fragment ions generated from an equimolar (10 μM) mixture of three cyclic peptides, achieving sequence coverage of 86%, 100%, and 75% for octreotide, desmopressin, and the structural analogue of desmopressin, respectively. In all detected fragment ion pairs, only 20% of the fragment ions are terminal ions, with most of the measured ions only detected by fragment correlation mass spectrometry. From the peak volumes in the covariance map, we calculated branching ratios of each disulfide bond fragmentation pathway, providing a direct measurement of the probability of each fragmentation without requiring alteration of the chemical structure of the analytes.

  View details for DOI 10.1021/acs.analchem.4c03202

  View details for PubMedID 39248333

• Fragment correlation mass spectrometry: Determining the structures of biopolymers in a complex mixture without isolating individual components. Proceedings of the National Academy of Sciences of the United States of America Li, Y., Cavet, G., Zare, R. N., Driver, T. 2024; 121 (32): e2409676121

  Abstract

  Fragment correlation mass spectrometry correlates ion pairs generated from the same fragmentation pathway, achieved by covariance mapping of tandem mass spectra generated with an unmodified linear ion trap without preseparation. We enable the identification of different precursors at different charge states in a complex mixture from a large isolation window, empowering an analytical approach for data-independent acquisition. The method resolves and matches isobaric fragments, internal ions, and disulfide bond fragments. We suggest that this method represents a major advance for analyzing structures of biopolymers in mixtures.

  View details for DOI 10.1073/pnas.2409676121

  View details for PubMedID 39074273

• Silica particles convert thiol-containing molecules to disulfides. Proceedings of the National Academy of Sciences of the United States of America Li, Y., Kolasinski, K. W., Zare, R. N. 2023; 120 (34): e2304735120

  Abstract

  Synthetic amorphous silica is a common food additive and a popular cosmetic ingredient. Mesoporous silica particles are also widely studied for their potential use in drug delivery and imaging applications because of their unique properties, such as tunable pore sizes, large surfaces areas, and assumed biocompatibility. Such a nanomaterial, when consisting of pure silicon dioxide, is generally considered to be chemically inert, but in this study, we showed that oxidation yields for different compounds were facilitated by simply incubating aqueous solutions with pure silica particles. Three thiol-containing molecules, L-cysteine, glutathione, and D-penicillamine, were studied separately, and it was found that more than 95% of oxidation happened after incubating any of these compounds with mesoporous silica particles in the dark for a day at room temperature. Oxidation increased over incubation time, and more oxidation was found for particles having larger surface areas. For nonporous silica particles at submicron ranges, yields of oxidation were different based on the structures of molecules, correlating with steric hindrance while accessing surfaces. We propose that the silyloxy radical (SiO•) on silica surfaces is what facilitates oxidation. Density functional theory calculations were conducted for total energy changes for reactions between different aqueous species and silicon dioxide surfaces. These calculations identified two most plausible pathways of the lowest energy to generate SiO• radicals from water radical cations H2O•+ and hydroxyl radicals •OH, previously known to exist at water interfaces.

  View details for DOI 10.1073/pnas.2304735120

  View details for PubMedID 37590411

• Glass surface as strong base, 'green' heterogeneous catalyst and degradation reagent CHEMICAL SCIENCE Li, Y., Huang, K., Morato, N. M., Cooks, R. 2021; 12 (28): 9816-9822

  Abstract

  Systematic screening of accelerated chemical reactions at solid/solution interfaces has been carried out in high-throughput fashion using desorption electrospray ionization mass spectrometry and it provides evidence that glass surfaces accelerate various base-catalyzed chemical reactions. The reaction types include elimination, solvolysis, condensation and oxidation, whether or not the substrates are pre-charged. In a detailed mechanistic study, we provide evidence using nanoESI showing that glass surfaces can act as strong bases and convert protic solvents into their conjugate bases which then act as bases/nucleophiles when participating in chemical reactions. In aprotic solvents such as acetonitrile, glass surfaces act as 'green' heterogeneous catalysts that can be recovered and reused after simple rinsing. Besides their use in organic reaction catalysis, glass surfaces are also found to act as degradation reagents for phospholipids with increasing extents of degradation occurring at low concentrations. This finding suggests that the storage of base/nucleophile-labile compounds or lipids in glass containers should be avoided.

  View details for DOI 10.1039/d1sc02708e

  View details for Web of Science ID 000667706500001

  View details for PubMedID 34349955

  View details for PubMedCentralID PMC8294000

• Reaction Acceleration at Solid/Solution Interfaces: Katritzky Reaction Catalyzed by Glass Particles ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Li, Y., Mehari, T., Wei, Z., Liu, Y., Cooks, R. 2021; 60 (6): 2929-2933

  Abstract

  The Katritzky reaction in bulk solution at room temperature is accelerated significantly by the surface of a glass container compared to a plastic container. Remarkably, the reaction rate is increased by more than two orders of magnitude upon the addition of glass particles with the rate increasing linearly with increasing amounts of glass. A similar phenomenon is observed when glass particles are added to levitated droplets, where large acceleration factors are seen. Evidence shows that glass acts as a "green" heterogeneous catalyst: it participates as a base in the deprotonation step and is recovered unchanged from the reaction mixture. Reaction acceleration at two separate interfaces is recognized in this study: i) air/solution phase acceleration, as is well known in microdroplets; ii) solid/solution phase, where such acceleration appears to be a new phenomenon.

  View details for DOI 10.1002/anie.202014613

  View details for Web of Science ID 000598637600001

  View details for PubMedID 33164315

• High-Throughput Screening of Reductive Amination Reactions Using Desorption Electrospray Ionization Mass Spectrometry ORGANIC PROCESS RESEARCH & DEVELOPMENT Logsdon, D. L., Li, Y., Sobreira, T., Ferreira, C. R., Thompson, D. H., Cooks, R. 2020; 24 (9): 1647-1657

  View details for DOI 10.1021/acs.oprd.0c00230

  View details for Web of Science ID 000574921200008

• Reaction acceleration at air-solution interfaces: Anisotropic rate constants for Katritzky transamination JOURNAL OF MASS SPECTROMETRY Li, Y., Mehari, T. F., Wei, Z., Liu, Y., Cooks, R. 2021; 56 (4): e4585

  Abstract

  To disentangle the factors controlling the rates of accelerated reactions in droplets, we used mass spectrometry to study the Katritzky transamination in levitated Leidenfrost droplets of different yet constant volumes over a range of concentrations while holding concentration constant by adding back the evaporated solvent. The set of concentration and droplet volume data indicates that the reaction rate in the surface region is much higher than that in the interior. These same effects of concentration and volume were also seen in bulk solutions. Three pyrylium reagents with different surface activity showed differences in transamination reactivity. The conclusion is drawn that reactions with surface-active reactants are subject to greater acceleration, as seen particularly at lower concentrations in systems of higher surface-to-volume ratios. These results highlight the key role that air-solution interfaces play in Katritzky reaction acceleration. They are also consistent with the view that reaction-increased rate constant is at least in part due to limited solvation of reagents at the interface.

  View details for DOI 10.1002/jms.4585

  View details for Web of Science ID 000549874500001

  View details for PubMedID 32686310

• Accelerated Forced Degradation of Therapeutic Peptides in Levitated Microdroplets PHARMACEUTICAL RESEARCH Li, Y., Hu, Y., Logsdon, D. L., Liu, Y., Zhao, Y., Cooks, R. 2020; 37 (7): 138

  Abstract

  Forced degradation is critical to probe the stabilities and chemical reactivities of therapeutic peptides. Typically performed in bulk followed by LC-UV or LC-MS analysis, this traditional workflow consists of a reaction/analysis sequence and usually requires half a day to several days to form and measure the desired amounts of degradants. A faster method is needed to study peptide degradation in a shorter time in order to speed up the drug development process.In the new rapid method developed in this study, peptide degradation occurs in levitated aqueous microdroplets using the Leidenfrost effect.This two-minute reaction/analysis workflow allows major degradation pathways of Buserelin, Octreotide, Desmopressin and Leuprorelin to be studied. The reactions include deamidation, disulfide bond cleavage, ether cleavage, peptide bond hydrolysis, and oxidation.The accelerated forced degradation method requires a minimal amount of therapeutic peptide per stress condition, and the appropriate extent of degradation can be readily generated in seconds by adjusting the droplet levitation time. Levitated microdroplets should be applicable in pharmaceutical development to rapidly determine the intrinsic stability of therapeutic peptides and to aid formulation development by screening the effects of excipients on the stability of the peptides. Graphical abstract.

  View details for DOI 10.1007/s11095-020-02868-y

  View details for Web of Science ID 000546938800001

  View details for PubMedID 32651732

• Accelerated Reaction Kinetics in Microdroplets: Overview and Recent Developments ANNUAL REVIEW OF PHYSICAL CHEMISTRY, VOL 71 Wei, Z., Li, Y., Cooks, R., Yan, X., Johnson, M. A., Martinez, T. J. 2020; 71: 31-51

  Abstract

  Various organic reactions, including important synthetic reactions involving C-C, C-N, and C-O bond formation as well as reactions of biomolecules, are accelerated when the reagents are present in sprayed or levitated microdroplets or in thin films. The reaction rates increase by orders of magnitude with decreasing droplet size or film thickness. The effect is associated with reactions at the solution-air interface. A key factor is partial solvation of the reagents at the interface, which reduces the critical energy for reaction. This phenomenon is of intrinsic interest and potentially of practical value as a simple, rapid method of performing small-scale synthesis.

  View details for DOI 10.1146/annurev-physchem-121319-110654

  View details for Web of Science ID 000530683600002

  View details for PubMedID 32312193

• A BODIPY-carbazole hybrid as a fluorescent probe: the design, synthesis, and discrimination of surfactants and the determination of the CMC values ANALYST Niu, X., Xu, Q., Li, A., Li, Y., Zhang, X., Zhang, Y., Xing, G. 2019; 144 (23): 6866-6870

  Abstract

  Surfactants play important roles in chemical industries and have become well-known environmental pollutants owing to their extensive use in different fields. In this work, we reported a fluorescent probe, namely, BDP-Zn2+ for the discrimination of four kinds of surfactants and the determination of CMC values. BDP-Zn2+ was composed of covalently linked BODIPY, carbazole, N,N-bis(2-pyridylmethyl)ethylenediamine (BPEA) and zinc ions to fabricate a novel push-pull molecular structure. Upon the addition of surfactants, the probe exhibited a turn-on fluorescence response and the emission was enhanced on increasing the surfactant concentrations. This indicated that the fluorescence intensity and the ratios of the emission at 607 nm to that at 514 nm as fingerprints could be used to identify the CMC values of the surfactants. Our current work provides an alternative method to efficiently discriminate different surfactants for the further studies of their physical and chemical functions.

  View details for DOI 10.1039/c9an01940e

  View details for Web of Science ID 000498558200005

  View details for PubMedID 31670735

• Accelerated Forced Degradation of Pharmaceuticals in Levitated Microdroplet Reactors CHEMISTRY-A EUROPEAN JOURNAL Li, Y., Liu, Y., Gao, H., Helmy, R., Wuelfing, W., Welch, C. J., Cooks, R. 2018; 24 (29): 7349-7353

  Abstract

  Forced degradation is a method of studying the stability of pharmaceuticals in order to design stable formulations and predict drug product shelf life. Traditional methods of reaction and analysis usually take multiple days, and include LC-UV and LC-MS product analysis. In this study, the reaction/analysis sequence was accelerated to be completed within minutes using Leidenfrost droplets as reactors (acceleration factor: 23-188) and nanoelectrospray ionization MS analysis. The Leidenfrost droplets underwent the same reactions as seen in traditional bulk solution experiments for three chemical degradations studied. This combined method of accelerated reaction and analysis has the potential to be extended to forced degradation of other pharmaceuticals and to drug formulations. Control of reaction rate and yield is achieved by manipulating droplet size, levitation time and whether or not make-up solvent is added. Evidence is provided that interfacial effects contribute to rate acceleration.

  View details for DOI 10.1002/chem.201801176

  View details for Web of Science ID 000434074600009

  View details for PubMedID 29653016

• Recent Progresses on Mitochondria-Targetable Fluorescent Probes CHINESE JOURNAL OF ORGANIC CHEMISTRY Li, Y., Lu, Z., Liu, M., Xing, G. 2016; 36 (5): 962-975

  View details for DOI 10.6023/cjoc201510012

  View details for Web of Science ID 000376573700007

• A pyrene-functionalized Zinc(II)-BPEA complex: sensing and discrimination of ATP, ADP and AMP RSC ADVANCES Xu, Q., Lv, H., Lv, Z., Liu, M., Li, Y., Wang, X., zhang, Y., Xing, G. 2014; 4 (88): 47788-47792

  View details for DOI 10.1039/c4ra07923j

  View details for Web of Science ID 000343035800087