100 Years of Progress with LONZA

In the past century, Lonza has developed from an hydroelectric plant into a specialized, globally operating chemical company. This growth was not a foregone conclusion but the fruit of innovative drive, market orientation, and bold decisions in difficult times. These attitudes are described in the following article that outlines the development of the product range from calcium carbide to organic intermediates and to highly sophisticated chemical and biotechnology-based exclusive manufacturing for leading life science companies

Question 1: Commentary Referring to the Statement "The Origin of Life can be Traced Back to the Origin of Kinetic Control” and the Question "Do You Agree with this Statement; and How Would You Envisage the Prebiotic Evolutionary Bridge Between Thermodynamic and Kinetic Control?” Stated in Section 1.1

The paper summarizes thoughts induced by some of the programmatic questions Pier Luigi Luisi posed for discussion at the Erice worksho

Chemical etiology of nucleic acid structure

The synthesis of potentially natural nucleic acid alternatives and comparison of some of their chemical properties with those of RNA and DNA have led to findings that we consider to be relevant in the context of a chemical etiology of nucleic acid structur

Chemie von α-Aminonitrilen. XVII. Oligo(nukleodipeptamidinium)-Salze

Experiments directed towards a chemical etiology of nucleic acids aim at uncovering facts that may help us to rationalize Nature\u27s choice of the RNA structure in the evolution of a genetic system. A strategy towards finding such facts is to synthesize potential nucleic acid alternatives and to systematically compare their functional properties (base pairing, nonenzymic replication, sequence- specific catalysis) on the chemical level with those of RNA. Nucleic acid alternatives are chosen by the criterion of whether their potential for constitutional self-assembly without enzymes is judged by chemical reasoning to be comparable to, or greater than, that of RNA. Alternatives which turn out to be functional could have (but have not or may have only temporarily) been chosen as a genetic system. Alternatives that are found to be non-functional can be dropped from the list of hypothetical RNA-competitors. Parallel to our work on nucleic acid alternatives based on hexopyranose sugars, we have studied potential pairing systems that contain dipeptide derivatives instead of sugar phosphates as building blocks of their backbones. Oligo-nucleodipeptamidinium salts of the constitutional type shown in Figure 3 can be interpreted as representing oligomers of corresponding nucleodipeptide nitriles which, in turn, can be derived from dipeptidic serine nitriles. This paper summarizes our observations on the synthesis and properties of thyminyl- and adenyl-derivatives of (L)-oligo-nucleodipeptamidinium salts (up to decamers) belonging to the constitutional type shown in Figures 9 and 10. Such oligomers are soluble in aqueous medium but turn out to be sensitive to hydrolysis at pH-values above 4 (half life of dimers at pH = 6, 1-3 h at room temperature, ca. 30 h at 0 °C). Neither in UV-spectroscopically determined mixing curves (c » 11 pM, pH = 4, 4 °C, 1 M NaCl) of mixtures of hexamers that contain complementary bases, nor in CD- spectra of (1 : 1) mixtures of the corresponding decamers (similar conditions) could we observe signs of adenine-thymine base pairing. Although these observations must be considered as preliminary since they are rather limited with regard to structural variations, conditions and observation methods, the properties observed for these materials discourage the view that such oligo-nucleodipeptamidinium salts might have been competitors to RNA. EINLEITUNG »Sie (die Naturstoffe) sind das Ergebnis einer drei Milliarden Jahre dauernden Entwicklung der lebendigen Welt und haben wáhrend einer langen Zeit die Auslese der Evolution überstanden. Ich bin überzeugt, dass sie immer eine Botschaft enthalten, und dass es unsere Aufgabe ist, diese zu entziffern.« (V. Prelog

Backbone-base inclination as a fundamental determinant of nucleic acid self- and cross-pairing

The crystal structure of the duplex formed by oligo(2′,3′-dideoxy-β-d-glucopyranosyl)nucleotides (homo-DNA) revealed strongly inclined backbone and base-pair axes [Egli,M., Pallan,P.S., Pattanayek,R., Wilds,C.J., Lubini,P., Minasov,G., Dobler,M., Leumann,C.J. and Eschenmoser,A. (2006) Crystal structure of homo-DNA and nature's choice of pentose over hexose in the genetic system. J. Am. Chem. Soc., 128, 10847–10856]. This inclination is easily perceived because homo-DNA exhibits only a modest helical twist. Conversely, the tight coiling of strands conceals that the backbone-base inclinations for A- (DNA and RNA) and B-form (DNA) duplexes differ considerably. We have defined a parameter ηB that corresponds to the local inclination between sugar-phosphate backbone and base plane in nucleic acid strands. Here, we show its biological significance as a predictive measure for the relative strand polarities (antiparallel, aps, or parallel, ps) in duplexes of DNA, RNA and artificial nucleic acid pairing systems. The potential of formation of ps duplexes between complementary 16-mers with eight A and U(T) residues each was investigated with DNA, RNA, 2′-O-methylated RNA, homo-DNA and p-RNA, the ribopyranosyl isomer of RNA. The thermodynamic stabilities of the corresponding aps duplexes were also measured. As shown previously, DNA is capable of forming both ps and aps duplexes. However, all other tested systems are unable to form stable ps duplexes with reverse Watson–Crick (rWC) base pairs. This observation illustrates the handicap encountered by nucleic acid systems with inclinations ηB that differ significantly from 0° to form a ps rWC paired duplex. Accordingly, RNA with a backbone-base inclination of −30°, pairs strictly in an aps fashion. On the other hand, the more or less perpendicular orientation of backbone and bases in DNA allows it to adopt a ps rWC paired duplex. In addition to providing a rationalization of relative strand polarity with nucleic acids, the backbone-base inclination parameter is also a determinant of cross-pairing. Thus, systems with strongly deviating ηB angles will not pair with each other. Nucleic acid pairing systems with significant backbone-base inclinations can also be expected to display different stabilities depending on which terminus carries unpaired nucleotides. The negative inclination of RNA is consistent with the higher stability of duplexes with 3′- compared to those with 5′-dangling ends

Euphrasia Eye Drops in Preterm Neonates With Ocular Discharge: A Randomized Double-Blind Placebo-Controlled Trial

Aim: To investigate whether the early administration of Euphrasia eye drops® in preterm neonates presenting with ocular discharge fosters the resolution of the ocular discharge and reduces the need for topical antibiotic therapy, as compared to placebo. Methods: We conducted a randomized double-blind placebo-controlled trial at the University Children's Hospital Bern, Switzerland. Preterm neonates with white, yellow, or green ocular discharge were included. Infants were randomly assigned (1:1) to the Euphrasia arm (Euphrasia eye drops®, Weleda AG, Arlesheim) or the placebo arm (NaCl 0.9%). Euphrasia or placebo was administrated at a dose of one drop in each eye four times a day over a period of 96 h. The primary outcome was the treatment success, defined as no ocular discharge at 96 h and no use of topical antibiotic therapy during the 96-h intervention. Results: A total of 114 neonates were screened and 84 were randomized. Among neonates in the Euphrasia arm, 22 (55.0%) achieved our primary outcome compared to 21 (51.2%) in the placebo arm (p = 0.85). In the Euphrasia arm, time to resolution of reddening tended to fall within the shorter bracket of 24 to 48 h (24 (92.3%) vs. 12 (80.0%) in the placebo arm, p = 0.34) and relapse or first signs of reddening during the 96-h intervention tended to be lower [3 (7.9%) eyes vs. 8 (18.2%) eyes in the placebo arm, p = 0.17]. Tearing at 96 h tended to be lower in the Euphrasia arm [5 (12.8%) eyes in the Euphrasia arm vs. 12 (27.3%) eyes in the placebo arm, p = 0.10]. Discussion: Euphrasia did not significantly improve treatment success, defined as no ocular discharge at 96 h and no use of topical antibiotic therapy during the 96-h intervention. However, results suggest that Euphrasia may be of benefit for symptoms such as reddening and tearing, and thus improve the comfort of patients. Trial Registration: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov) NCT04122300 and at the portal for human research in Switzerland SNCTP000003490. Keywords: Euphrasia drops; complementary medicine; congenital nasolacrimal duct obstruction; ocular discharge; preterm neonate

Monopyrrolische VorHiufer fur die Synthese des Uroporp hyrinogen -octani trils

Syntheses of the pre-uroporphinoid monopyrrolic derivatives porphobilinogen dinitrile, deaminomethyl-porphobilinogen dinitrile and 5-deaminomethyl-2-hydroxymethyl-porphobilinogen dinitrile make multiple use of the crystalline Mannich salt dimethyl- -methylidene-iminiumjodide as areagent for the introduction of cyanomethyl and ,B-cyanoethylside chains at the ,B-positionof the pyrrol nucleus. The paper is the first in a series of reports on the chemistry of uroporphyrinogen octanitrile