Research

Our group is passionate about advancing the frontiers of chemical biology, computational chemistry, and data-driven science. We combine experimental and theoretical approaches to tackle challenging problems at the interface of chemistry, biology, and data science.

Research Topics

Bioorthogonal Chemistry

We focus on the development and application of bioorthogonal reactions, which enable chemical transformations inside living systems without disrupting native biochemical processes. Our work spans reaction discovery, mechanistic understanding, and biomedical applications. This research is conducted in close collaboration with the Mikula Lab (TU Wien) and others, such as the Franzini Lab (University of Utah) on isonitrile click chemistry.

Representative publications:

Uncovering the Key Role of Distortion in Bioorthogonal Tetrazine Tools That Defy the Reactivity/Stability Trade-Off

We revealed how pyridyl substitution in tetrazines enables fast, stable bioorthogonal tools by leveraging molecular distortion, overcoming the classic reactivity/stability trade-off.

Chemoselectivity of Tertiary Azides in Strain-Promoted Alkyne-Azide Cycloadditions

We revealed how steric Pauli repulsion in tertiary azides reshapes chemoselectivity with dibenzocyclooctynes, enabling highly selective dual labeling in copper-free click chemistry.

Reaction Mechanisms

We investigate fundamental organic reaction mechanisms using state-of-the-art computational chemistry tools. Our goal is to provide a detailed understanding of reaction pathways, thereby also enabling the rational design of new transformations.

Representative publications:

Mechanistic Insights into the Reaction of Amidines with 1,2,3-Triazines and 1,2,3,5-Tetrazines

We uncovered that 1,2,3-triazines and 1,2,3,5-tetrazines react with amidines via nucleophilic addition/N₂ elimination/cyclization, overturning the expected Diels–Alder paradigm and explaining their unique orthogonal reactivity.

How the Lewis Base F^– Catalyzes the 1,3-Dipolar Cycloaddition between Carbon Dioxide and Nitrilimines

We reveal that F⁻ catalysis in the CO₂–nitrilimine 1,3-dipolar cycloaddition works by activating the nitrilimine, not CO₂, raising its HOMO and shrinking the frontier-orbital gap to accelerate cycloaddition.

Energy Decomposition

Our group heavily applies energy decomposition analysis (EDA) methods to gain a deeper understanding of the forces that govern chemical bonding and reactivity. By separating interactions into electrostatic, orbital, dispersion, and steric contributions, we provide mechanistic insight that goes beyond total energies. Additionally, we develop new EDA methods to enhance interpretability and applicability to complex systems.

Representative publication:

Unraveling the Bürgi-Dunitz Angle with Precision: The Power of a Two-Dimensional Energy Decomposition Analysis

This study pioneers a 2D Energy Decomposition Analysis approach, mapping the potential energy surface of CN⁻ attack on (CH₃)₂C═O and uncovering the interplay of Pauli repulsion, strain, and interaction energies behind the Bürgi–Dunitz angle.

CompChem Tools

Our group develops tools that make computational chemistry easier and more accessible. This includes improved automated 3D structure generation from simple inputs as well as our web-based molecular viewer ChemView, designed for fast and intuitive visualization of quantum chemical results. These tools support researchers in exploring structures and reactivity without technical barriers.

Representative publication:

ChemView: A Web-Based Molecular Viewer for Quantum Chemical Results (Beta)

Explore the beta version of ChemView, our interactive molecular viewer designed for fast and intuitive visualization of quantum chemical results directly in the browser. Built to make computational chemistry data more accessible and user-friendly.

autoDIAS: a python tool for an automated distortion/interaction activation strain analysis

We developed autoDIAS, a Python tool that automates distortion/interaction activation strain (DIAS) analysis, handling setup, fragment detection, and data extraction with minimal user intervention.

Collaborators

We believe that collaborations are essential for great science. We are grateful for our current and past collaborators, and are always open to new partnerships. Please reach out if you are interested in working together!

Current

Prof. Thomas Mindt (University of Vienna)
Prof. Hannes Mikula (TU Wien)
Assoc. Prof. Raphael Franzini (University of Utah)
Prof. Ken Houk (UCLA)
Assoc. Prof. Frederic Friscourt (University of Bordeaux)
Assist. Prof. Xin Hong (Zhejiang University)
Prof. Sharifuddin Bin Md Zain (University of Malaya)

Past

Prof. Kathrin Lang (ETH Zürich)
Prof. Dale Boger (Scripps Research Institute)
Assist. Prof. Maren Podewitz (TU Wien)
Prof. F. Matthias Bickelhaupt (VU Amsterdam)
Prof. Israel Fernández (Universidad Complutense de Madrid)
Dr. Johann Hlina (TU Graz)
Assist. Prof. Trevor Hamlin (VU Amsterdam)
Prof. Peter Gärtner (TU Wien)
Assoc. Prof. Michael Schnürch (TU Wien)
Prof. Matthias Herth (University of Copenhagen)
Prof. M.G. Finn (Georgia Institute of Technology)
Prof. P.G. Harran (UCLA)
Prof. Matthias Barz (Leiden University)
Prof. Vassil Delchev (University of Plovdiv)

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