Circular dichroism of designed peptide helices and β-hairpins: analysis of trp- and tyr-rich peptides

VCD versus ECD spectroscopy. Peptides rich in aromatic residues yield anomalous far-UV electronic circular dichroism (ECD) spectra that preclude secondary structure assignment. The utility of vibrational circular dichroism (VCD) in conformation analysis is demonstrated by using a set of well-defined peptide helices and hairpins containing proximal aromatic residues

Les harraga algériens

Des Algériens, principalement des jeunes hommes, tentent de quitter leur pays, sans passeport ni visa, sur des barques, au péril de leur vie. En dialecte maghrébin, on nomme ces candidats à l’émigration harraga (les “brûleurs”), car ils “brûlent” les frontières et les étapes nécessaires à une migration légale. En outre, s’ils arrivent en Europe, ils détruisent, ils “brûlent” leurs papiers d’identité pour tenter d’échapper à l’expulsion. Après les hittistes des années 1980 et ceux qui ont rejoint les groupes islamistes armés durant le conflit des années 1990, les harraga sont érigés au rang de figure symbolisant le désespoir de la jeunesse algérienne durant les années 2000. Ils sont invoqués comme preuve ultime des dysfonctionnements qui touchent le pays. (Premier paragraphe

Exploring Molecular Interactions : Synthesis and Studies of Clip-Shaped Molecular Hosts

Molecular recognition via noncovalent interactions plays a key role in many biological processes such as antigen-antibody interactions, protein folding, the bonding and catalytic transformation of substrates by enzymes, etc. Amongst these noncovalent interactions, electrostatic interactions, hydrogen bonding, π-π interactions, and metal-to-ligand bonding are the most prominent. Exploring noncovalent interactions in host-guest systems that range from small hydrocarbon systems to more complex systems is the main motivation of this thesis. The present study involves the design, synthesis and characterization of clip-shaped molecules as host structures, and an examination of their binding properties with a variety of guests using NMR spectroscopy. Several clips with a hydrocarbon or glycoluril backbone were synthesized. The binding of cations to small, hydrocarbon-based clips suggests that binding is enhanced by the rigidity and cooperativity between the two sidewalls of the clip. Binding is also very much dependant on the solvent properties. Glycoluril-based clips built with aromatic sidewalls provide a deep cavity for binding guest molecules. The binding properties of these hosts were studied with several guests such as cations, Lewis acids and Lewis bases. Lewis basic binding sites in the acenaphthene-terminated clip were dominating in guest binding. Complexation-induced conformational changes in the wall-to-wall distance were observed for this clip. In contrast, for a porphyrin-terminated clip with metal centers, very strong binding to a series of Lewis basic guests of various sizes into the clip cavity was observed. Conformational locking of guests with long alkyl chains was achieved, suggesting that, this clip could be useful as a potential molecular tool for the structural characterization of acyclic molecules with several stereogenic centers. This porphyrin clip was also shown to bind substituted fullerenes in the cavity

Exploring Molecular Interactions : Synthesis and Studies of Clip-Shaped Molecular Hosts

Molecular recognition via noncovalent interactions plays a key role in many biological processes such as antigen-antibody interactions, protein folding, the bonding and catalytic transformation of substrates by enzymes, etc. Amongst these noncovalent interactions, electrostatic interactions, hydrogen bonding, π-π interactions, and metal-to-ligand bonding are the most prominent. Exploring noncovalent interactions in host-guest systems that range from small hydrocarbon systems to more complex systems is the main motivation of this thesis. The present study involves the design, synthesis and characterization of clip-shaped molecules as host structures, and an examination of their binding properties with a variety of guests using NMR spectroscopy. Several clips with a hydrocarbon or glycoluril backbone were synthesized. The binding of cations to small, hydrocarbon-based clips suggests that binding is enhanced by the rigidity and cooperativity between the two sidewalls of the clip. Binding is also very much dependant on the solvent properties. Glycoluril-based clips built with aromatic sidewalls provide a deep cavity for binding guest molecules. The binding properties of these hosts were studied with several guests such as cations, Lewis acids and Lewis bases. Lewis basic binding sites in the acenaphthene-terminated clip were dominating in guest binding. Complexation-induced conformational changes in the wall-to-wall distance were observed for this clip. In contrast, for a porphyrin-terminated clip with metal centers, very strong binding to a series of Lewis basic guests of various sizes into the clip cavity was observed. Conformational locking of guests with long alkyl chains was achieved, suggesting that, this clip could be useful as a potential molecular tool for the structural characterization of acyclic molecules with several stereogenic centers. This porphyrin clip was also shown to bind substituted fullerenes in the cavity

Determination of the Absolute Configurations of Chiral Drugs Using Chiroptical Spectroscopy

Chiroptical spectroscopy has emerged as a promising tool for the determination of absolute configurations and predominant conformations of chiral molecules in academic laboratories. This promise has led to the adaption of chiroptical spectroscopic methods as valuable tools in chiral drug discovery research programs of the pharmaceutical industry. Most major pharmaceutical companies have invested in in-house chiroptical spectroscopy applications and reported successful outcomes. In the context of continuously increasing applications of chiroptical spectroscopy for chiral molecular structure determination, a review of recent developments and applications for chiral drugs is presented in this manuscript

Exploring Molecular Interactions : Synthesis and Studies of Clip-Shaped Molecular Hosts

Molecular recognition via noncovalent interactions plays a key role in many biological processes such as antigen-antibody interactions, protein folding, the bonding and catalytic transformation of substrates by enzymes, etc. Amongst these noncovalent interactions, electrostatic interactions, hydrogen bonding, π-π interactions, and metal-to-ligand bonding are the most prominent. Exploring noncovalent interactions in host-guest systems that range from small hydrocarbon systems to more complex systems is the main motivation of this thesis. The present study involves the design, synthesis and characterization of clip-shaped molecules as host structures, and an examination of their binding properties with a variety of guests using NMR spectroscopy. Several clips with a hydrocarbon or glycoluril backbone were synthesized. The binding of cations to small, hydrocarbon-based clips suggests that binding is enhanced by the rigidity and cooperativity between the two sidewalls of the clip. Binding is also very much dependant on the solvent properties. Glycoluril-based clips built with aromatic sidewalls provide a deep cavity for binding guest molecules. The binding properties of these hosts were studied with several guests such as cations, Lewis acids and Lewis bases. Lewis basic binding sites in the acenaphthene-terminated clip were dominating in guest binding. Complexation-induced conformational changes in the wall-to-wall distance were observed for this clip. In contrast, for a porphyrin-terminated clip with metal centers, very strong binding to a series of Lewis basic guests of various sizes into the clip cavity was observed. Conformational locking of guests with long alkyl chains was achieved, suggesting that, this clip could be useful as a potential molecular tool for the structural characterization of acyclic molecules with several stereogenic centers. This porphyrin clip was also shown to bind substituted fullerenes in the cavity

Chiral Molecular Structures of Substituted Indans: Ring Puckering, Rotatable Substituents, and Vibrational Circular Dichroism

The chiral molecular structures of four different substituted indans, namely, (S)-1-methylindan, (R)-1-methylindan-1-d, (R)-1-aminoindan, and (S)-1-indanol, were investigated using experimental vibrational absorption and vibrational circular dichroism spectra and corresponding spectra predicted using quantum chemical (QC) calculations. All of these molecules possess two ring puckering conformations, with ring puckering leading to the pseudoequatorial substituent being approximately four times more abundant over that leading to the pseudoaxial substituent. The amino group in 1-aminoindan has three conformations arising from the rotation of NH2 group, for each ring puckering conformation, resulting in a total of six conformations. Whereas 1-indanol in the nonhydrogen-bonding solvent CCl4 also has six conformations similar to those of 1-aminoindan, 1-indanol in the hydrogen-bonding solvent DMSO-d6 adopts numerous conformations, of which 30 conformers are considered to have at least ∼1% or more population. In DMSO solution, ring puckering leading to pseudoequatorial substituent accounts for 77% population and 23% for pseudoaxial substituent. The QC spectra predicted for the geometry optimized conformers are found to be in excellent quantitative agreement with corresponding experimental spectra in all of the molecules considered. The procedures suggested in this work are hoped to provide successful pathways for future chiral molecular structural analyses