Dr. Ivan Tubert-Brohman

Department of Chemistry
University of Basel
Klingelbergstrasse 80
CH-4056 Basel, Switzerland
+41 (0)61 207 09 42

I am a post-doctoral researcher in the group of Prof. Markus Meuwly at the University of Basel during the period 2007-2008, thanks to funding by a Marie Curie fellowship. I will be working on the development of methods for the simulation of iridium-catalyzed asymmetric hydrogenation reactions, in collaboration with the Pfaltz group.

Asymmetric catalysis

Asymmetric catalysis, and specifically asymmetric hydrogenation, is a field that has recently received intense attention, as manifested by the Royal Swedish Academy of Sciences' decision to award half of the 2001 Nobel Prize in Chemistry to William Knowles and Ryoji Noyori for their work in asymmetric hydrogenation. This was part of a series of developments that started with Wilkinson's discovery of an efficient homogeneous catalyst for hydrogenation 1 in the 1960s, followed by more active reagents such as Crabtree's iridium-based catalyst 2 in the 1970s, which can be used for hydrogenating even tetra-substituted unfunctionalized olefins. The latter catalyst became the basis for the recent development of chiral phosphinooxazoline (PHOX)-based catalysts 3 by Pfaltz and coworkers in Basel, which are versatile catalysts for asymmetric hydrogenation of both functionalized and unfunctionalized double bonds.

For previous computational work on Pfaltz's catalysts, see

Mazet, C.; Smidt, S. P.; Meuwly, M.; Pfaltz, A. J. Am. Chem. Soc. 2004, 126, 14176-14181.

The goal is to develop new and efficient molecular mechanics and molecular dynamycs methods for the simulation of these types of catalytic reactions, and for predicting the selectivity of different ligands. We will draw on previous work on reactive MD, reactive force fields, and force fields for transition metals and adapt them.

Research interests

My previous work has touched on several areas of computational chemistry and chemical information.

QM/MM simulation of enzymatic reactions. I have worked on Monte Carlo Quantum Mechanical/Molecular Mechanical simulations of reactions catalyzed by fatty acid amide hydrolase (FAAH), chorismate mutase, and artificially designed proteins.

As an example, the work on FAAH revealed a striking concerted reaction mechanism that may explain the effect of certain mutations on the selectivity of the enzyme towards different substrates. The figures below show the two proposed mechanisms; A for the wild-type protein, and B for the mutant; the free energy surface for the rate-determining step for mechanism A, and a snapshot of the transition state during the simulation.

Elucidation of Hydrolysis Mechanisms for Fatty Acid Amide Hydrolase and Its Lys142Ala Variant via QM/MM Simulations. Tubert-Brohman, I.; Acevedo, O.; Jorgensen, W. L. J. Am. Chem. Soc. 2006, 128, 16904-16913. doi:10.1021/ja065863s

Semiempirical methods. I have developed improved semiempirical methods by using statistical bond and group equivalents, by modifying the core repulsion function, and by introducing orthogonalization corrections to the SCF calculation.

A major part of this work was the parameterization of the PDDG/PM3 semiempirical molecular orbital method to the halogens, silicon, phosphorus, and sulfur. This entailed gathering a test set of 1500 molecules with known heats of formation; overall, the PDDG/PM3 method was the most accurate we tested, with mean absolute errors at least 25% lower than PM3. It can handle highly oxidized sulfur compounds such as sulfones well without sacrificing accuracy for the low-valence functional groups. From the halogen study, the PDDG/PM3 method resulted in an accuracy comparable to DFT and gave good results for SN2 reactions.

Extension of the PDDG/PM3 Semiempirical Molecular Orbital Method to Sulfur, Silicon, and Phosphorus. Tubert-Brohman, I.; Guimarães, C. R. W.; Jorgensen, W. L. J. Chem. Theory Comput. 2005, 1, 817-823. doi:10.1021/ct0500287

Extension of the PDDG/PM3 and PDDG/MNDO Semiempirical Molecular Orbital Methods to Halogens. I. Tubert-Brohman; C.R.W. Guimarães, M.P. Repasky & W.L. Jorgensen J. Comput. Chem. 2004, 25, 138-150. doi:10.1002/jcc.10356

Molecular modeling of solvent effects. I have worked on the study of steric and solvent effects on pKa via density functional theory (DFT) combined with Monte Carlo statistical mechanical simulations. Unpublished results show how steric effects are crucial for the pKa of bulky pyridines in solution, and how explicit solvent is require to simulate those effects.

Virtual screening. I have used genetic algorithms to optimize a descriptor set for doing similarity searching for screening molecules with possible activity towards HIV reverse transcriptase. Ongoing work in this area involves docking calculations and scoring, and collaboration with experimental groups to assay some promising candidates.

Computer-Assisted Organic Synthesis. I collaborated in the design and implementation of a client-server Computer-Assisted Organic Synthesis system, which includes pattern recognition, a language interpreter, a graphical user interface, and a knowledge base. A website on this (very outdated) is at http://ivan.tubert.org/caos/.

More information

Full CV (PDF)

Personal website with pictures, stories, hobbies, blog, etc.

Advice for Mexicans who want to go to graduate school abroad (in Spanish).