De Novo Design of secondary structures: Synthesis and conformational studies

Chemists have long sought to extrapolate the power of biological catalysis and recognition to synthetic systems. These efforts have focused largely on low molecular weight catalysts and receptors; however, biological systems themselves rely almost exclusively on polymers, proteins and RNA, to perform complex chemical functions. Proteins and RNA are unique in their ability to adopt compact, well-ordered conformations, and specific folding provides precise spatial orientation of the functional groups that comprise the “active site”. These features suggest that identification of new polymer backbones with discrete and predictable folding propensities (“foldamers”) will provide a basis for design of molecular machines with unique capabilities. The foldamer approach complements current efforts to design unnatural properties into polypeptides and polynucleotides. The aim of this thesis is the synthesis and conformational studies of new classes of foldamers, using a peptidomimetic approach. Moreover their attitude to be utilized as ionophores, catalysts, and nanobiomaterials were analyzed in solution and in the solid state. This thesis is divided in thematically chapters that are reported below. It begins with a very general introduction (page 4) which is useful, but not strictly necessary, to the expert reader. It is worth mentioning that paragraph I.3 (page 22) is the starting point of this work and paragraph I.5 (page 32) isrequired to better understand the results of chapters 4 and 5. In chapter 1 (page 39) is reported the synthesis and conformational analysis of a novel class of foldamers containing (S)-β3-homophenylglycine [(S)-β3-hPhg] and D- 4-carboxy-oxazolidin-2-one (D-Oxd) residues in alternate order is reported. The experimental conformational analysis performed in solution by IR, 1HNMR, and CD spectroscopy unambiguously proved that these oligomers fold into ordered structures with increasing sequence length. Theoretical calculations employing ab initio MO theory suggest a helix with 11-membered hydrogenbonded rings as the preferred secondary structure type. The novel structures enrich the field of peptidic foldamers and might be useful in the mimicry of native peptides. In chapter 2 cyclo-(L-Ala-D-Oxd)3 and cyclo-(L-Ala-DOxd) 4 were prepared in the liquid phase with good overall yields and were utilized for bivalent ions chelation (Ca2+, Mg2+, Cu2+, Zn2+ and Hg2+); their chelation skill was analyzed with ESI-MS, CD and 1HNMR techniques and the best results were obtained with cyclo-(L-Ala-D-Oxd)3 and Mg2+ or Ca2+. Chapter 3 describes an application of oligopeptides as catalysts for aldol reactions. Paragraph 3.1 concerns the use of prolinamides as catalysts of the cross aldol addition of hydroxyacetone to aromatic aldeydes, whereas paragraphs 3.2 and 3.3 are about the catalyzed aldol addition of acetone to isatins. By means of DFT and AIM calculations, the steric and stereoelectronic effects that control the enantioselectivity in the cross-aldol addition of acetone to isatin catalysed by L-proline have been studied, also in the presence of small quantities of water. In chapter 4 is reported the synthesis and the analysis of a new fiber-like material, obtained from the selfaggregation of the dipeptide Boc-L-Phe-D-Oxd-OBn, which spontaneously forms uniform fibers consisting of parallel infinite linear chains arising from singleintermolecular N-H···O=C hydrogen bonds. This is the absolute borderline case of a parallel β-sheet structure. Longer oligomers of the same series with general formula Boc-(L-Phe-D-Oxd)n-OBn (where n = 2-5), are described in chapter 5. Their properties in solution and in the solid state were analyzed, in correlation with their attitude to form intramolecular hydrogen bond. In chapter 6 is reported the synthesis of imidazolidin-2- one-4-carboxylate and (tetrahydro)-pyrimidin-2-one-5- carboxylate, via an efficient modification of the Hofmann rearrangement. The reaction affords the desired compounds from protected asparagine or glutamine in good to high yield, using PhI(OAc)2 as source of iodine(III).

La psicologia della Gestalt. Ricerche teoriche e sperimentali sulla percezione sonora e musicale (1890-1939)

The aim of the present work is a historical survey on Gestalt trends in psychological research between late 19th and the first half of 20th century with privileged reference to sound and musical perception by means of a reconsideration of experimental and theoretical literature. Ernst Mach and Christian von Ehrenfels gave rise to the debate about Gestaltqualität which notably grew thanks to the ‘Graz School’ (Alexius Meinong, Stephan Witasek, Anton Faist, Vittorio Benussi), where the object theory and the production theory of perception were worked out. Stumpf’s research on Tonpsychologie and Franz Brentano’s tradition of ‘act psychology’ were directly involved in this debate, opposing to Wilhelm Wundt’s conception of the discipline; this clearly came to light in Stumpf’s controversy with Carl Lorenz and Wundt on Tondistanzen. Stumpf’s concept of Verschmelzung and his views about consonance and concordance led him to some disputes with Theodor Lipps and Felix Krueger, lasting more than two decades. Carl Stumpf was responsible for education of a new generation of scholars during his teaching at the Berlin University: his pupils Wolfgang Köhler, Kurt Koffka and Max Wertheimer established the so-called ‘Berlin School’ and promoted the official Gestalt theory since the 1910s. After 1922 until 1938 they gave life and led together with other distinguished scientists the «Psychologische Forschung», a scientific journal in which ‘Gestalt laws’ and many other acoustical studies on different themes (such as sound localization, successive comparison, phonetic phenomena) were exposed. During the 1920s Erich Moritz von Hornbostel gave important contributions towards the definition of an organic Tonsystem in which sound phenomena could find adequate arrangement. Last section of the work contains descriptions of Albert Wellek’s studies, Kurt Huber’s vowel researches and aspects of melody perception, apparent movement and phi-phenomenon in acoustical field. The work contains also some considerations on the relationships among tone psychology, musical psychology, Gestalt psychology, musical aesthetics and musical theory. Finally, the way Gestalt psychology changed earlier interpretations is exemplified by the decisive renewal of perception theory, the abandon of Konstanzannahme, some repercussions on theory of meaning as organization and on feelings in musical experience.