Download Fundamentals and - 17th International Symposium on Chiral

International Symposium on Chirality
Short Intensive Courses
9.00-16.30 Sunday September 11,
Centro Santa Elisabetta, Science Campus, Parco Area delle ScienzeParma, Italy
1. Spectroscopic methods for the investigation of chiral compounds
Instructors
G. Uccello Barretta
Enantiodiscrimination by NMR spectroscopy
L. Di Bari
Fundamentals of CD for the determination of absolute configuration and
enantiomeric composition
N. Berova
Structural analysis based on conventional and fluorescence detected CD exciton
coupling
G. Pescitelli
Computation of CD spectra
2. High performance enantioselective separation processes: theoretical and practical aspects
Instructors
V. Schurig
Enantioseparations by using capillary GC: present state of the art and future trends
D. W. Armstrong
An introduction and survey of enantioselective liquid chromatography
B. Chankvetadze
Enantioseparations by using capillary electrophoresis: present state of the art and
future trends
3. Chirality in biorecognition
Instructors
J. Caldwell
Fundamentals of the biological importance of chirality
J. Gal
Chirality as a modulator of therapeutic and toxic effects of drugs
R. Corradini
Chirality in DNA targeting
4. Preparative enantioseparation through HPLC: fundamentals and industrial applications
Instructors
F. Dondi
Linear and nonlinear
chromatography
chromatography:
an
introduction
to
preparative
A. Cavazzini
Fundamentals of nonlinear chromatography
M. Morbidelli
Simulated moving bed chromatography for chiral separations
E. Francotte
Preparative enantioselective chromatography: basic principles and guidelines
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.
Research
Nina
Berova
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 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 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 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 postgenome 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
F. Dondi, A. Cavazzini, M. Morbidelli, E. Francotte
Abstract
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 (University of Ferrara)
Fundamentals of nonlinear chromatography
Prof. M. Morbidelli
Simulated moving bed chromatography for chiral separations
Dr. E. Francotte
Preparative enantioselective chromatography: basic principles and guidelines