Evan R. Williams
· Professor of ChemistryVerifiedUniversity of California, Berkeley · Department of Chemical and Biomolecular Engineering
Active 1986–2026
About
Professor Evan R. Williams is the Principal Investigator at the University of California, Berkeley, with a distinguished academic background including a B.S. from the University of Virginia (1984) and a Ph.D. from Cornell University (1990). He completed a National Science Foundation Postdoctoral Fellowship at Stanford University from 1989 to 1991. Throughout his career, Professor Williams has received numerous prestigious awards such as the National Science Foundation Young Investigator Award (1992), Arnold and Mabel Beckman Foundation Young Investigator (1992), Analytical Chemists of Pittsburgh Award (1992), Exxon Education Foundation Research Award (1993), American Society for Mass Spectrometry Research Award (1994), Alexander von Humboldt Senior Scientist Award (1999), Amgen Faculty Award (2004), and the John B. Fenn Award for Distinguished Contribution in Mass Spectrometry (2022). He has also served as a Visiting Professor in the Department of Physics and Astronomy at the University of Aarhus, Denmark (2005). Professor Williams holds several key roles at UC Berkeley, including Faculty Scientist in the Earth Sciences Division at Lawrence Berkeley National Laboratory, Faculty Director of the QB3/Chemistry Mass Spectrometry Center, and Associate Director of the Center for Analytical Biotechnology. His professional memberships include the American Chemical Society (ACS) and the American Society for Mass Spectrometry (ASMS). His research group focuses on advancing mass spectrometry techniques, particularly charge detection mass spectrometry (CDMS), to study biomolecules such as proteins, RNA-protein complexes, and other macromolecules. The group develops new analytical hardware and methods to gain insights into molecular binding sites, stoichiometry, stability, folding kinetics, and aggregation relevant to human disease and diverse molecular systems.
Research topics
- Organic chemistry
- Chemistry
- Chemical physics
- Physical chemistry
- Chromatography
Selected publications
ChemRxiv · 2026-01-29
articleOpen accessThe formation mechanism of hydrogen peroxide (H 2 O 2 ) in water microdroplets has been hotly debated, with proposals ranging from strong interfacial electric fields, discharge between droplets (i.e., microlightning), and reactions with ozone or dissolved oxygen. Here, we quantify H 2 O 2 formation from positive, negative, and neutral droplets under oxygen- and ozone-free conditions. Neutral water droplets formed by condensation and positive electrospray droplets do not produce detectable amounts of H 2 O 2 (detection limit ~60 nM), whereas negative electrospray droplets generate up to tens of micromolar H 2 O 2 . The H 2 O 2 concentration in negative droplets scales linearly with spray current indicating the role of excess OH– that is electrochemically produced by the electrospray process itself. More than 140 MJ/mol of energy is needed to produce micromolar concentrations of H 2 O 2 in negative electrospray. Intrinsic interfacial electric field and inter-droplet discharge mechanisms are inconsistent with the pronounced asymmetry in H 2 O 2 production with droplet polarity. Instead, the results support a pathway for formation of hydroxyl radicals (OH • ) that is unique to activated negatively charged droplets, wherein electron ejection from OH– occurs during droplet fission and upon contact with a stainless-steel surface. This mechanism leads to abundant OH • that combine to form H2O2. These findings suggest a new mechanism for formation of H 2 O 2 from aqueous microdroplets and further demonstrate that H 2 O 2 generation is not spontaneous or a result of an inherent property of the uncharged air–water interface in the absence of reactive oxygen or activation.
2025-07-16
peer-reviewJournal of the American Society for Mass Spectrometry · 2025-03-11 · 2 citations
articleOpen accessSenior authorCorrespondingProtein aggregation is a factor in a multitude of neurodegenerative diseases and aggregates of protein-based biotherapeutics can cause toxicity in vivo and adverse patient outcomes. Monoclonal antibody (M)–fluorophore (F) complexes with four different antibody sequences and masses of ∼680 kDa were analyzed using size-exclusion chromatography (SEC) and mass spectrometry using both quadrupole-time-of-flight (QTOF) and charge detection mass spectrometry (CDMS). Higher-order aggregates were not resolved using SEC, but species as large as the MF2 complex and M5F3 were resolved using QTOF and CDMS, respectively. Results from three freeze–thaw cycles and long-term heat stress indicate that both aggregation and degradation occurs. Two of the antibodies form a critical M2F complex that is sensitive to thermal stress, whereas the other two antibodies undergo degradation and formation of the assembled MF2 complex in response to freeze–thaw and thermal stressors, respectively. These data show that small differences in mAb sequence can result in significant changes to the aggregation and degradation pathways and highlight the promise of combined mass spectrometry approaches for characterizing how various stress factors affect the stability and aggregation propensity of mAbs.
Journal of the American Chemical Society · 2025-05-24 · 4 citations
articleOpen accessSenior authorCorrespondingFission of highly charged micrometer-sized and larger droplets has been investigated using optical methods, but until recently, direct measurements of spontaneous fission of submicrometer droplets have not been possible. Charge detection mass spectrometry is used to track the mass, charge, and energy per charge of aqueous nanodrops that undergo evaporative water loss while they are trapped for up to 4 s. 154 of the 846 trapped nanodrops (18.2%) with charges ranging from 44 to 158% of the Rayleigh limit underwent fission. Although these spontaneous fission processes are highly heterogeneous, four distinct fission pathways that occur over times ranging from a few ms to 100s of ms with ejection of just a few to hundreds of progeny droplets were identified. One is a "continuous" pathway in which many small progeny droplets with progressively less charge are sequentially emitted over the course of ∼25 to 150 ms. Prompt and sequential prompt pathways in which one or a limited number of progeny droplets carry away a significant fraction of the precursor charge are the most common. "Prefission" events in which emission of just a few charges prior to a larger prompt fission event occur for some nanodrops charged above the Rayleigh limit, and these events appear to have similarities to "foreshocks" that often occur shortly prior to major earthquakes.
ACS Central Science · 2025-04-04 · 25 citations
articleOpen accessSenior author36 ion in many previous experiments indicate that many results that have been used to support hypotheses about unusual chemistry and the effects of high intrinsic electric fields at microdroplet surfaces may require a more thorough evaluation.
Journal of Biological Chemistry · 2025-05-01
articleOpen accessSenior authorCalmodulin (CaM) plays a crucial role in Ca2+-dependent signal transduction. When Ca2+ binds to CaM, it induces a conformational change that creates a hydrophobic patch essential for interacting with the calmodulin-binding domain (CaMBD) of target proteins. The structures of the CaM/CMBD complex can be categorized into extended and collapsed models, with stoichiometry ranging from 1 to 2 CMBD, which reflecting the hydrodynamic property of CaM. Despite decades of efforts, the model of this complex remains to be elucidated solely through structural determination.
ACS Central Science · 2025-10-31 · 4 citations
articleOpen accessSenior authorCorrespondingNeutral water microdroplets formed by condensation were introduced into a mass spectrometer with a standard stainless-steel capillary atmospheric interface. Placing volatile samples near the mass spectrometer inlet led to spectra comparable to those of electrospray ionization of the same compounds. Neutral microdroplets introduced into a charge detection instrument through a nearly identical atmospheric sampling interface resulted in charged microdroplets with diameters between 165 nm (∼3,000 charge detection threshold) and 2.8 μm (200,000+ charges). The vast majority of 100,000+ aqueous microdroplets analyzed were positively charged. Aerodynamic acceleration led to average velocities of ∼270 m/s and ∼210 m/s for the smallest and largest microdroplets, respectively, with corresponding energies ranging from a few MeV to 300+ MeV for the largest microdroplets. Current measured on the capillary and other results indicate that interactions between the neutral microdroplets and the capillary can strip off hundreds of thousands of electrons to form positively charged droplets. Negatively charged microdroplets indicate a minor process in which neutral microdroplets are broken up into smaller microdroplets of both polarities. The MeV+ energy involved in these interactions is sufficient to drive many chemical reactions and may lead to unusual and unexpected chemistry when analysis is done using mass spectrometers with atmospheric sampling interfaces.
Journal of Controlled Release · 2025-05-18 · 3 citations
articleOpen accessSenior authorCorrespondingLipid nanoparticles (LNPs) are effective delivery systems for RNA therapeutics, yet their intrinsic heterogeneity in size and composition make them challenging to characterize. Charge detection mass spectrometry (CDMS) was used to rapidly weigh thousands of individual LNPs. Diameter distributions of empty LNPs from CDMS and cryo-TEM measurements are in excellent agreement demonstrating that these particles are sufficiently stable in the high vacuum environment of the mass spectrometer for accurate mass analysis. A similarly prepared mRNA-packaged LNP sample has a peak mass at ∼70 MDa, 31 MDa higher than that of the empty LNP sample. Four freeze-thaw (FT) cycles of the mRNA-LNPs results in a peak mass at ∼26.5 MDa, indicating significantly degraded LNPs. The degraded LNPs are about 28 % of the population of the mRNA-LNP sample after the first FT cycle. A non-linear least squares fitting routine was developed to convolve the mass distribution of the LNP core with a function that describes the packaging distribution to fit the mRNA-LNP data. Two models of the lipid core mass distribution were used to obtain the distribution of mRNA in the packaged LNPs. These two models provide a lower and upper limit to the average mRNA packaging of 43 and 107 mRNA copies, consistent with a rough estimate of an average of 62 mRNA copies obtained from cryo-TEM images. These results demonstrate the potential for label-free, rapid characterization of mass, diameter, packaging, and stability of LNPs with CDMS.
Angewandte Chemie International Edition · 2025-03-11 · 14 citations
articleOpen accessSenior authorCorrespondingAbstract Formation of energetic species at the surface of aqueous microdroplets, including abundant hydroxyl radicals, oxidation products, and ionized N 2 and O 2 gas, has been previously attributed to the high electric field at the droplet surface. Here, evidence for a new mechanism for electronic excitation involving electron emission from negatively charged water droplets is shown. Droplet evaporation can lead to the emission of ions and droplet fission, but unlike positively charged droplets, negatively charged droplets can also shed charge by electron emission. With nanoelectrospray, no anions or negatively charged droplets are produced with a positive electrospray potential. In contrast, abundant O 2 +• and H 3 O + (H 2 O) are formed with negative electrospray. When toluene vapor is introduced with negative electrospray, abundant toluene radical cations and fragments are produced. Both O 2 +• and toluene radical cations are produced with pneumatic nebulization. The electrons produced from evaporating negatively charged droplets can be accelerated by an external electric field in electrospray, or by the field generated between droplets with opposite polarities produced by pneumatic nebulization. This electron emission/ionization mechanism leads to electronic excitation >10 eV, and it may explain some of the surprising chemistries that were previously attributed to the high intrinsic electric field at the surface of aqueous droplets.
Analytical Chemistry · 2025-12-31 · 2 citations
articleSenior authorCorresponding
Recent grants
Ion Hydration and Nanocalorimetry in Mass Spectrometry
NSF · $546k · 2013–2017
Ion Hydration and Nanodrops in Mass Spectrometry
NSF · $570k · 2022–2026
Ion Hydration and New Structural Methods in Mass Spectrometry
NSF · $450k · 2010–2013
Integrated Methods for Structural Elucidation of Proteins and Macromolecular Comp
NIH · $1.0M · 2012–2017
Ion Hydration and Nanocalorimetry in Mass Spectrometry
NSF · $966k · 2016–2023
Frequent coauthors
- 84 shared
Jos Oomens
University of Amsterdam
- 50 shared
Jeremy T. O’Brien
- 49 shared
Matthew F. Bush
University of Washington
- 42 shared
Richard J. Cooper
Norwich Research Park
- 41 shared
Zijie Xia
University of Pennsylvania
- 40 shared
Conner C. Harper
University of California, Berkeley
- 39 shared
Sven Heiles
University of Giessen
- 37 shared
John Kuriyan
Vanderbilt University
Labs
Not provided
Awards & honors
- National Science Foundation Postdoctoral Fellowship (1989-19…
- National Science Foundation Young Investigator Award (1992)
- Arnold and Mabel Beckman Foundation Young Investigator (1992…
- Analytical Chemists of Pittsburgh Award (1992)
- Exxon Education Foundation Research Award (1993)
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