The transition from a nonmetallic to a metallic state typically involves changes in electron mobility and the formation of a conduction band, a process that in solids is often associated with defining crystal structure and temperature-dependent properties. However, liquids defy some of these constraints due to their inherent molecular disorder and dynamism. Professor Jungwirth and colleagues have long focused on the peculiar case of alkali metals dissolved in liquid ammonia, a classical system where metallic behavior emerges abruptly as the solution changes color from blue to a lustrous golden hue. This visual transformation heralds the formation of a conduction network from free electrons donated by alkali metal atoms, yet until now, the intermediate stages within this transition have remained elusive.

Central to this new investigation is the application of state-of-the-art molecular dynamics simulations that can faithfully capture the behavior of electrons and ions on ultrafast timescales and at atomic resolution. The simulations reveal a previously overlooked regime where the system does not settle into either the metallic or nonmetallic state but instead exhibits a rapid “flipping” or oscillation between these electronic configurations. This "third phase" defies traditional equilibrium descriptions and compels a reconsideration of the criteria defining phase transitions in conductive liquids. The switching occurs on the scale of tens of femtoseconds (one femtosecond being one quadrillionth of a second), orders of magnitude faster than conventional experimental techniques have been able to probe.

Professor Jungwirth underscores the novelty of this phenomenon: “No one had previously realized that such a system might oscillate so rapidly between these two fundamentally different electronic states. These dynamics had simply not been accounted for in theoretical or experimental frameworks before.” This insight opens new vistas for understanding how conduction emerges and dissolves in disordered environments, potentially impacting fields as diverse as materials science, condensed matter physics, and electrochemistry.

Capturing such rapid transitions experimentally presents a formidable challenge. The temporal resolution required transcends the capabilities of conventional spectroscopy methods. To address this, the IOCB Prague team intends to harness ultrafast laser technology, which can deliver pulses short enough to act as snapshots of these fleeting electronic states. PhD student Marco Vítek, first author of the study, explains, “Our aim is to develop an experimental setup using ultrafast laser pulses that can effectively ‘freeze’ the system’s state at different moments, allowing us to observe these flips directly. Some of these laser sources are already available at our institute, bringing this ambitious goal within reach.”

Collaboration with internationally renowned institutions, including the University of Oxford, the Faculty of Mathematics and Physics at Charles University, and the J. Heyrovský Institute of Physical Chemistry, has been instrumental in pushing the boundaries of computational and experimental prowess required for this research. Together, the teams have employed a combination of high-performance computing and sophisticated quantum mechanical models to achieve unprecedented simulation accuracy.

The implications of this discovery extend beyond merely redefining a classic physical transition. The intermittent, ultrafast switching points to a novel quantum-mechanical process intrinsic to liquids containing dissolved alkali metals. It suggests that conductivity in such systems does not arise from a smooth crossover but rather from a dynamic equilibrium with rapid fluctuations. This challenges the universality of static phase diagrams and compels theorists to incorporate time-dependent variables into models of liquid metals.

If experimentally verified, this phenomenon could have broad technological ramifications. Understanding ultrafast electronic state fluctuations could inform the design of novel materials with tailored conduction properties, potentially impacting energy storage, catalysis, and sensor technologies. Moreover, it may necessitate new interpretations of data gathered from systems where fast electronic processes play a critical role.

The study, published in the prestigious journal Nature Communications, represents a milestone in physical chemistry and condensed matter physics. The research leverages computational simulation/modeling methodologies that capture phenomena inaccessible through classical experimental setups alone. This computational insight, complemented by planned ultrafast spectroscopic experiments, defines a new milestone in the exploration of liquid state physics.

Of particular interest is the methodological framework developed by the team, which integrates electronic structure calculations with molecular dynamics to simulate real-time electron behavior in complex liquid environments. This multiscale modeling offers a blueprint for future studies investigating transient phenomena in other chemical and physical systems.

In summary, the discovery of a rapid flipping behavior between electrolyte and metallic states in ammonia solutions of alkali metals opens a fresh theoretical and experimental frontier. It challenges prevailing dogma, invites a reexamination of the metal-nonmetal transition, and bridges the gulf between chemical physics and ultrafast spectroscopy. This study signals a profound advance in our grasp of the liquid metal state and sets the stage for experimental verification that could rewrite textbooks on physical phase transitions.

Subject of Research: Physical sciences – Chemistry – Chemical physics / Molecular dynamics

Article Title: Rapid flipping between electrolyte and metallic states in ammonia solutions of alkali metals

News Publication Date: 8-May-2025

Web References:
http://dx.doi.org/10.1038/s41467-025-59071-z

References:
Vitek, M.; Igor Rončević; Marsalek, O.; Schewe, H. C.; Jungwirth, P. Rapid Flipping between Electrolyte and Metallic States in Ammonia Solutions of Alkali Metals. Nat. Commun. 2025, 16 (1).

Image Credits:
Photo: Tomáš Belloň/IOCB Prague

Keywords:
Chemical physics, Molecular dynamics

Alopecia areata arises when the immune system mistakenly targets hair follicles, resulting in inflammation and subsequent hair loss. Current treatment options are largely centered around corticosteroids, which while effective can also lead to bothersome side effects. The scientists’ new approach with itaconate derivatives offers a novel mechanism that addresses underlying inflammation without the associated risks typical of steroid treatments. The efficacy of their research has garnered attention, indicating a significant step forward in drug discovery and development for alopecia areata.

The study reveals how their developed prodrugs not only alleviate symptoms but also exhibit properties that encourage hair regrowth. Among the compounds studied, SCD-153 has shown particular promise; pre-clinical testing demonstrated its capability to not only reduce inflammation but also activate dormant hair follicles, promoting new hair growth. This transformation of hair follicles from a resting phase to an active growth phase is critical, offering a pathway to restoring hair for individuals afflicted with alopecia areata.

One of the challenges faced by researchers in developing effective therapies is ensuring that active substances can penetrate cell membranes efficiently. The naturally occurring itaconate presents this barrier, limiting its effectiveness. Dr. Majer’s team ingeniously developed a solution in the form of prodrugs that can be metabolized into their active forms within the body. By creating derivatives that can bypass the cell membrane, they have opened the door to effective oral administration rather than relying solely on topical treatments.

Clinical findings have shown that these compounds demonstrate a favorable absorption profile when tested in animal models. This suggests that further development could focus on creating oral formulations, which are generally more convenient for patients than creams or ointments. The versatility of being administrable as tablets can greatly enhance patient compliance and therapeutic outcomes, marking a significant advancement in drug delivery systems related to autoimmune treatment.

The implications of this research extend beyond alopecia areata, as the principles of using itaconate-type prodrugs may have applications in various inflammatory conditions driven by immune dysregulation. As scientists gain greater understanding of the biochemical pathways involved in such disorders, new avenues for therapeutic intervention may be explored, paving the way for broader applications of this technology.

Pharmaceutical company SPARC has taken notice of these developments, acquiring licensing rights to utilize the patented technology surrounding the itaconate prodrugs. Their commitment to bringing the compound SCD-153 into clinical trials marks a crucial step towards making this potential treatment accessible to patients. Currently, they are recruiting individuals for phase 1 trials, a pivotal stage in establishing safety and efficacy in humans.

The hope is that these clinical trials will yield positive outcomes, leading to a new standard of care for those suffering from alopecia areata. The existing treatments could soon be complemented or replaced by this innovative approach, significantly improving the quality of life for patients who often endure emotional and psychological distress due to hair loss.

The research team’s ongoing focus on interdisciplinary collaboration exemplifies the growing trend where different scientific fields converge to solve complex health issues. The successful integration of chemistry, biochemistry, and clinical research not only enhances the immediate prospects for alopecia treatment but also sets a precedent for future research in other autoimmune disorders.

In conclusion, the work spearheaded by Dr. Majer and his collaborators heralds a new era in the treatment of alopecia areata, embodying the principles of precision medicine. The promising data from these studies reflects a commitment to innovation that is essential for addressing chronic conditions that impact so many lives. As this research progresses towards clinical application, it stands not only to change how alopecia is treated but also to inspire future developments in therapeutic interventions across a spectrum of inflammatory diseases.

As we await further developments from clinical trials, the scientific community remains optimistic about the possibility of relief for many who suffer from the anxiety of autoimmune disorders. The meticulous research and strategic partnerships that have driven this advancement provide a beacon of hope in the ever-evolving landscape of modern medicine.

Subject of Research: Development of prodrugs for the treatment of alopecia areata
Article Title: Discovery of Orally Available Prodrugs of Itaconate and Derivatives
News Publication Date: 23-Jan-2025
Web References: DOI Link
References: Lee, C. B., Šnajdr, I., Tenora, L., Alt, J., Gori, S., Krečmerová, M., Maragakis, R. M., Paule, J., Tiwari, S., Iyer, J., Talwar, R., Garza, L., Majer, P., Slusher, B. S., & Rais, R. Discovery of Orally Available Prodrugs of Itaconate and Derivatives.
Image Credits: Photo: Tomáš Belloň/IOCB Prague

Keywords: Alopecia areata, Autoimmune disorders, Itaconate derivatives, Drug discovery, Pharmaceutical advancements, Prodrugs, Hair loss treatment, Immunology, Precision medicine, Clinical trials, Drug delivery systems, Biochemical research.