Short Intensive Courses

Short Course n. 1- Spectroscopic methods for the investigation of chiral compounds

Overview: The aim of this short course is to introduce the fundamentals of NMR and CD spectroscopic methods for the investigation of chiral compounds. The course will cover from the basis of NMR and CD methods of determination of enantiomeric compositions and absolute configurations to the structural analysis based on conventional and fluorescence detected CD exciton coupling and computation of CD spectra .

Instructors:

Prof. Gloria Uccello Barretta Professor of Organic Chemistry, University of Pisa , Italy .

Prof. Lorenzo Di Bari Professor of Organic Chemistry, University of Pisa , Italy.

Prof. Nina Berova Research Professor, Senior Research Scientist, Department of Chemistry, Columbia University , New York . Editor of Chirality.

Dr.Gennaro Pescitelli, Ph.D. University of Pisa

Lecture abstracts:

Prof.G.Uccello Barretta - Enantiodiscrimination by NMR spectroscopy

The discussion is aimed to point out the most significant characteristics of NMR methods of determination of enantiomeric purities and absolute configurations, focusing attention on the applied aspects: procedure of use, precautions, advantages and disadvantages. Besides the general features, some examples will be analyzed which are of particular interest from a historical, innovative or illustrative point of view, giving a general overview of literature data.

Short history of NMR enantiodiscrimination methods. Basis of enantiomers differentiation by NMR spectroscopy: intrinsic equivalence of enantiotopic nuclei and intrinsic non-equivalence of diastereotopic nuclei. The three fundamental classes of chiral auxiliaries which are employed to make distinguishable NMR active nuclei of enantiomers: Chiral Derivatizing Agents (CDAs), Chiral Solvating Agents (CSAs), and Chiral Lanthanide Shift Reagents (CLSRs).

Chiral Derivatizing Agents : selected organic CDAs, phosphorus chiral and achiral derivatizing agents, selenium reagents, organometallic CDAs. Chiral Solvating Agents: selected organic CSAs, macrocyclic and macromolecular CSAs. Chiral Lanthanide Shift Reagents and mixed diamagnetic and paramagnetic chiral auxiliaries.

Prof. Lorenzo Di Bari “ Fundamentals of CD for the determination of absolute configuration and enantiomeric composition”

Abstract not yet available

Prof. Nina Berova “ Structural analysis based on conventional and fluorescence detected CD exciton coupling”

The lecture will focus on the basic principles of the exciton coupling in electronic CD and its application in structural analysis. The exciton chirality approach is now one of the most sensitive and versatile microscale CD methods for determining the absolute configuration and detecting subtle conformational changes in solution in a nonempirical manner. A brief survey will be presented on the recently introduced CD chromophores with enhanced sensitivity and versatility, such as substituted styrenes, tetraarylpophyrins, and others with “red shifted” UV-vis absorption. Selected metalloporphyrins that have attracted a widespread attention as receptors for chiral recognition and have recently been employed in supramolecular excition chirlaity studies will also be discussed.

The second part of the lecture will present more recent developments in the Fluorescence Detected Circular Dichroism (FDCD). Due to its enhanced sensitivity and selectivity, the detection of CD in emission is becoming a valuable alternative to conventional CD measurements. The discussion will include examples illustrating the advantage of FDCD over the conventional CD and a brief analysis of the undesired effects of polarization of fluorescence that may lead to artifacts. Finally, some recent technological improvements, for example, a development of the ellipsoidal mirror FDCD detector that overcomes the problems related to photoselection and provides enhanced detection sensitivity will also be presented.

Dr. G. Pescitelli “Computation of CD spectra”

Abstract not yet available

Short Course n. 2- High performance enantioselective separation processes: theoretical and practical aspects.

Overview: The short course is intended to introduce the basic concepts of enantioselective chromatographic (GC and HPLC) and electrophoretic techniques, to show their applications and outline present state of the art and future trends.

Instructors:

Prof. Volker Schurig, Inst f Organische Chemie-University of Tübingen, Germany.- Editor, Journal of Chromatography A-Recipient of the Chirality Medal 2004.

Prof. Daniel W. Armstrong , Department of Chemistry, Iowa State University , USA- Editor, Analytical Chemistry. Recipient of the Chirality Medal 2003.

Prof. Bezhan Chankvetadze , Molecular Recognition and Separation Science Laboratory, Tbilisi State University , Georgia- Editor, Journal of Pharmaceutical and Biomedical Analysis.

Lecture abstracts:

Prof. V. Schurig : Enantioseparations by using capillary GC: present state of the art and future trends

Definition of chromatography. Terms used in chromatography. Retention, selectivity and efficiency governing resolution. Van Deemter and Golay equation. Direct and indirect separation of enantiomers by chromatography - advantages and disadvantages. Definitions of enantiomeric compositions (ee, er, ec) - advantages and disadvantages. Statistics of the use of chiral stationary phases and separation methods. Chirbase.

Separation of enantiomers by GC:

History. Classification of chiral stationary phases: hydrogen-bonding CSPs, metal-complexation CSPs, inclusion-type CSPs (cyclodextrins).  Four peak parameters in enantioselective GC. Coalescence phenomena. Thermodynamics of enantiorecognition. Enthalpy-entropy-compensation.

Isoenantioselective temperature. Enantiomerization studies. Multidimensional stopped flow technique. Comprehensive GC x GC.  Practical applications in pheromone and flavour research, environmental chirality, extraterrestrial chirality. Separation of halogenated hydrocarbons and unfunctionalized hydrocarbons. Enantiomer labelling. Semipreparative enantiomeric separation. Unified enantioselective chromatography in open capillary columns.

Prof. D.W. Armstrong : An Introduction and Survey of Enantioselective Liquid Chromatography

Abstract not yet available

Prof. B. Chankvetadze : Enantioseparations by using capillary electrophoresis: present state of the art and future trends

Short history of enantioseparations using capillary electromigration techniques. Comparative characteristics of chromatographic and electromigration techniques from the viewpoint of enantioseparations. Enantioselective and nonselective phenomena in chiral CE.

Basic principles and descriptors of enantioseparations in capillary electrophoresis and capillary electrochromatography. Major groups of chiral selectors used in capillary electrophoresis: cyclodextrins, chiral surfactants, macrocyclic antiobiotics, crown ethers, non-cyclic oligo- and polysaccharides, proteins, etc.

Adjustment of separation selectivity in chiral CE; Enantiomer migration order; Chiral CE-MS coupling; Quantitative aspects of chiral CE; Applications of chiral CE in pharmaceutical and biomedical analysis, food analysis, environmental analysis, etc.

Chiral separations in capillary electrochromatography: advantages and problems. CEC in surface modified open tubular and packed capillaries; Major group of chiral stationary phases used in CEC: low molecular weight chiral selectors, chiral polymers, chiral ion-exchangers, etc. Comparison between particulate and monolithic chiral stationary phases. Applications of chiral CEC.

Short Course n. 3- Chirality in biorecognition

Overview: The aim of this short course is to introduce the fundamentals of chiral discrimination in the interaction of small molecules, and in particular of drugs, with biopolymers such as protein or DNA, and to analyze the principal models developed to understand the crucial role played by chirality in biololgical processes. The course will cover from ‘classical' drug targets such as enzymes and receptors to the post-genome DNA targeting approach and will show the principal methodologies and latest results for these type of studies.

Instructors:

Prof. John Caldwell Dean, Faculty of Medicine University of Liverpool , UK- Editor of Chirality

Prof. Joseph Gal Professor of Medicine, Pharmacology, and Pathology - University of Colorado School of Medicine- Director, Therapeutic Drug Monitoring and Toxicology Laboratory - University of Colorado , Denver , USA.

Prof. Roberto Corradini Professor of Organic and Bioorganic Chemistry, University of Parma, Italy .

Prof. J. Caldwell Fundamentals of the biological importance of chirality.

The lecture will introduce the phenomenon of chirality in a biological context, the chiral technologies in the industrial context and chiral discrimination by protein targets like receptors, enzymes and some examples of chiral discrimination in DNA.

Prof. J. Gal Chirality As A Modulator Of Therapeutic And Toxic Effects Of Drugs.

Differences between enantiomerically related drug molecules in their actions and disposition are common and such enantioselectivity has serious consequences for the therapeutic efficacy and toxicity of drugs and for the development of new drugs. In this lecture the causes and manifestations of this phenomenon will be discussed. The nature of drug-receptor binding will be examined in detail, including the physicochemical forces and molecular complementarity involved in the binding of drugs to the biological macromolecules (receptors) that mediate drug action. The role of chirality in modulating such binding will be discussed, including the Easson-Stedman Hypothesis and quantitative aspects (Pfeiffer's rule, Eudismic analysis). The clinical consequences of enantioselective drug-receptor interactions will then be examined using relevant examples to illustrate the important role of chirality in drug therapy.

Prof. R. Corradini. Chirality in DNA Targeting

Post-genomic therapies rely on the knowledge of DNA/RNA sequences and of their function; nucleic acids can also be viewed as possible targets. Small molecules, metal complexes, oligomeric compounds and artificial nucleotides can be used for the specific targeting of DNA. However, due to the chiral nature of nucleic acids, stereochemistry plays a central role in the efficiency of these molecules. Examples for each class of molecules will be discussed. In particular, the role of chirality in the efficiency of oligonucleotide and their artificial analogues will be discussed, on the basis of a general model considering stereochemistry, its effect on helicity and consequences for their possible use as antisense or anti-gene drugs. The principal methodologies for the study of the interaction of chiral compounds with DNA will be illustrated.

Short Course n. 4- Preparative Enantioseparation through HPLC: Fundamentals and Industrial Applications

Overview: The aim of this workshop is to present the fundamentals and the current practice of preparative enantioseparations via HPLC.

The course begins with an overview of linear and nonlinear chromatography. Typical phenomena commonly observed when high-concentrated samples are injected in chromatographic columns will be described in relation to the thermodynamics (namely, adsorption isotherms) and the kinetics (mass transfer effects) of the fundamental processes controlling the separation.

A survey of adsorption isotherm models (single-component and competitive) often used in HPLC works will be presented. The most important chromatographic techniques in use to empirically evaluate the adsorption isotherms will be described, with particular emphasis to so-called Frontal Analysis and Inverse Method approaches. Advantages and drawbacks of these different techniques will be discussed. How the thermodynamic information is used to solve the differential mass balance equations describing the evolution of the band profiles in the chromatographic medium up to their elution will be presented. This represents the key for chromatographic model validation, based on the comparison between simulated and experimental peaks. Practical instrumental arrangements to best measure adsorption data through HPLC will be described.

How this basic thermodynamic information is used also for the scaling-up of the chromatographic processes from lab- to industrial-scale will be discussed.

The last part of the course deals with SMB technology and industrial applications of presented knowledge. SMB constitutes a continuous separation process that is quickly becoming, in some cases, a serious alternative to more traditional separation techniques. The workshop covers the fundamentals of SMB processes – both from a theoretical and practical point of view – by starting on real cases of enantiomeric separations.

Instructors:

Prof. Francesco Dondi. - Professor of Analytical Chemistry- Department of Chemistry-University of Ferrara , Italy

Dr. Alberto Cavazzini Researcher- Department of Chemistry - University of Ferrara , Italy

Prof. Massimo Morbidelli Professor of Chemical Reaction Engineering -Institute for Chemical and Bioengineering, ETH, Zürich , Switzerland .

Dr. Eric Francotte Novartis Institutes for Biomedical Research, Discovery Technologies Basel, Switzerland .

Prof. F. Dondi Linear and nonlinear chromatography: An introduction to preparative chromatography

Dr. A. Cavazzini Fundamentals of nonlinear chromatography

Prof. M. Morbidelli Simulated moving bed chromatography for chiral separations

Dr. E. Francotte Preparative enantioselective chromatography: basic principles and guidelines