Research Areas

Dr. Leonardo S. Santos was born and grew up in Santos (Sao Paulo state, Brazil). In 1993, he went to Brasilia where he studied chemistry at the University of Brasilia. In 1997, he moved to Campinas (Brazil) for his master degree (1999) and PhD appointments at Unicamp University (2003) under the direction of Dr. R. A. Pilli. During his PhD, he went to Chicago, USA, for a PhD sandwich program at the University of Chicago with Dr. Viresh H. Rawal (2001–2002). He then took up a postdoctoral position at the Thomson Mass Spectrometry Laboratory at the University of Campinas, where along with Dr. M. N. Eberlin he introduced ESI-MS-based mechanistic studies to Brazil. In 2005, he moved to Germany joining the group of Dr. Jürgen O. Metzger at Carl von Ossietzky Universität for a postdoctoral appointment. In Germany, he continued to study organic reaction mechanisms of organocatalyzed polymerization through new methodologies using mass spectrometry (ESI-MS).

He is currently full-professor (Titular) at the Chemistry Institute of Natural Resources at Talca University (Chile), and established the Laboratory of Asymmetric Synthesis (LAS) in 2006 as well as the Center for Nanoscience (CeNS) in 2010 to develop a 6-years collaborative project with Fraunhofer Institute (Germany) in Chile. His research targets are selected on the basis of novel molecular architecture, important biological activity and interesting mechanism of action. Merging natural products chemistry, chemical synthesis and mechanisms using ESI-MS, these principles form the foundation for Dr. Santos’ research and educational programs. Furthermore, he continues to develop new methodologies based on new catalysts and the study of mechanistic pathways involving organometallic compounds through API-MS experiments.

It is my conviction that Chemistry is, to a great extent, about chemical reactions - developing them, understanding them, and using them to make interesting molecules. Much of the activity in my research is directed at discovering new ways to make complex molecules. This includes (a) the design of unique strategies to particular families of structurally-intricate molecules, often possessing useful pharmacological properties, or (b) the invention of new reactions, or the development of useful aspects of known reactions, particularly their asymmetric variants, and finally (c) the development of new catalysts and the study of mechanistic pathways involving organometallic compounds through APCI/ and ESI-MS experiments. Man's fascination with natural substances goes back to ancient times. With the discovery of salicin from willow tree extracts and the development of aspirin in 1899, the art of exploiting natural products became a molecular science. The discovery of penicillin in 1928 and its subsequent development as an anti-infective agent represents another breakthrough in the history of natural products, and marked the beginning of a new era in drug discovery, in which bacteria and fungi were added to the plant kingdom as sources for biologically active compounds. Today, with marine organisms and other living creatures as additional sources of active compounds, the chemistry and biology of natural products represents a major avenue to drug discovery and development. Indeed, a large portion of today's major drugs have their origins in nature. It is, therefore, not surprising that one of the most flourishing and rewarding frontiers in modern science is the study of the chemistry and biology of natural products. But man's imagination does not stop at the frontiers defined by nature. With the ever-increasing power of organic synthesis, the synthetic organic chemist is poised to make important contributions by inventing and developing new enabling technologies for the generation of isolated natural products, but also of designed small organic molecules of broad structural diversity for binding to and modulating the function of biological targets.

In our laboratory, in pursuing the total synthesis of natural products, new synthetic strategies and methods are sought to solve the problems at hand, but also to remain as enabling technologies for chemistry, biology and medicine. Targets are selected on the basis of novel molecular architecture, important biological activity and interesting mechanism of action. Merging natural products chemistry, chemical synthesis and chemical biology, these principles form the foundation for our research and educational programs.

With regard to strategies, we have devised concise new routes to several families of natural products. Our objective is devise short, high yielding syntheses, through strategies that examine interesting aspects of structure and reactivity in an asymmetric way.

We have been actively involved in the development and study of useful synthetic methods. Electrospray ionization mass spectrometry (ESI-MS) is rapidly becoming an important technique for mechanistic studies of chemical reactions in solution including homogeneously catalyzed reactions and high-throughput screening of homogeneous catalysts.

Lewis Acid Enhanced Ethene Dimerization and Alkene Isomerization — ESI-MS Identification of Acitve Species

Probing the Mechanism of Ziegler-Natta Polymerization by On-Line Monitoring of Reaction through ESI-MS

On-line Monitoring of Brookhart Polymerization Reactions by ESI-MS

Chemoselective Aromatic Azido Reduction with Concomitant Aliphatic Azide Employing Al/Gd Triflates/NaI

Using APCI-MS(/MS) we have intercepted, characterized and proved the mechanism by Ionic Liquid species are vaporize at ambient conditions from heated (100-600 °C) solvent droplets. No evidence for vaporization of ILs as single neutral carbenes (for Im+) or AH species was observed.

Probing The Mechanism of Ionic Liquids distillation by APCI-MS

We are also actively pursuing the design of new methods for asymmetric synthesis based upon ruthenium, rhodium, palladium and titanium organometallics compounds. Finally, we have begun a program aimed at the development of new catalysts for organic synthesis.

First example of bioreduction of beta-carboline imines

Palladium Asymmetric Reduction of b-Carboline Imines Mediated by Chiral Auxiliaries

Schematic uptake of functionalized QDs/PAMAM supramolecular complexes by folate receptors in the phospholipidic bilayer of cancer cells. PAMAM dendrimer was functionalized using folate molecules in order to promote selective cellular uptake and imaging specificity.

QDs/PAMAM-FA nanocomposite