Results: From October 2014 to July 2015, 14 patients [5M; (FEV1, 60 (18)%] met the criteria for mannitol: inadequate response to current mucolytic (11/14 were on DNase) and declining lung function. At baseline patients used a range of airway clearance (Acapella n =4; PEP n=8). Three patients stopped mannitol prior to the 2 month follow up (chest tightness, increased cough). At 2 months (n =11) there was no change in FEV1 [mean(SD) diff from baseline −0.64(13)%], there was a trend towards a lower LCI [mean(SD) diff from baseline −1.07(1.9)]. There were no consistent changes in HRQoL. Patients did not report any perceived changes in ease of clearance, satisfaction with mucolyic or fatique from using mannitol at 2 months. Prior to 6 month follow up two further patients stopped mannitol (chest tightness, perceived lack of benefit). For patients with 6 month data (n =8), the trend towards lower LCI at 6 months was still evident [mean(SD) diff from baseline −1.2(2.4)]. All other outcomes remained unchanged. Conclusion: Mannitol may contribute to opening up previously poorly ventilated areas.

Polymers of all categories and the monomers necessary for their syntheses offer numerous opportunities for beginning students of organic chemistry to be exposed to and learn the details of foundational principles of organic chemistry. This view on polymer chemistry is the focus of three chapters in a new book, "Organic Chemistry Principles in Context: A Story Telling Historical Approach." The chapter to follow is based on information from this book focused only on radicals and not on condensation polymers, which are also discussed in the book. The discussion on radicals yields information normally presented in undergraduate organic chemistry courses but in the context of the importance of polymers. In this manner polymer yield insight into the addition of radicals to double bonds, the reactivity of polymers in hydrogen abstraction, the beta-scission reactions of radicals and how resonance stabilization of radicals blocks the radical polymerization of propylene.

The helix is a critical conformation exhibited by biological macromolecules and plays a key role in fundamental biological processes. Biological helical polymers exist in a single helical sense arising from the chiral effect of their primary units-for example, DNA and proteins adopt predominantly a right-handed helix conformation in response to the asymmetric conformational propensity of D-sugars and L-amino acids, respectively. In using these homochiral systems, nature blocks our observations of some fascinating aspects of the cooperativity in helical systems, although when useful for a specific purpose, "wrong" enantiomers may be incorporated in specific places. In synthetic helical systems, on the contrary, incorporation of non-racemic chirality is an additional burden, and the findings discussed in this review show that this burden may be considerably alleviated by taking advantage of the amplification of chirality, in which small chiral influences lead to large consequences. Peptide nucleic acid (PNA), which is a non-chiral synthetic DNA mimic, shows a cooperative response to a small chiral effect induced by a chiral amino acid, which is limited, however, due to the highly flexible nature of this oligomeric chimera. The lack of internal stereochemical bias is an important factor which makes PNA an ideal system to understand some cooperative features that are not directly accessible from DNA.

The helix is a critical conformation exhibited by biological macromolecules and plays a key role in fundamental biological processes. Biological helical polymers exist in a single helical sense arising from the chiral effect of their primary units-for example, DNA and proteins adopt predominantly a right-handed helix conformation in response to the asymmetric conformational propensity of D-sugars and L-amino acids, respectively. In using these homochiral systems, nature blocks our observations of some fascinating aspects of the cooperativity in helical systems, although when useful for a specific purpose, "wrong" enantiomers may be incorporated in specific places. In synthetic helical systems, on the contrary, incorporation of non-racemic chirality is an additional burden, and the findings discussed in this review show that this burden may be considerably alleviated by taking advantage of the amplification of chirality, in which small chiral influences lead to large consequences. Peptide nucleic acid (PNA), which is a non-chiral synthetic DNA mimic, shows a cooperative response to a small chiral effect induced by a chiral amino acid, which is limited, however, due to the highly flexible nature of this oligomeric chimera. The lack of internal stereochemical bias is an important factor which makes PNA an ideal system to understand some cooperative features that are not directly accessible from DNA.

Saluting the sergeant: Phg-BTA (see scheme) cooperatively self-assembles into helical aggregates and shows unprecedented racemization behavior in the presence of base. In thermodynamically controlled conditions, the addition of a small amount of chiral auxiliary to this mixture results in a deracemization reaction and a final enantiomeric excess of 32 %. A theoretical model is presented to understand in detail the results obtained.

Helical handedness and the twist and tilt parameters of the base pairs in duplex DNA can be affected by base sequence variation and change in environmental conditions as occurs in the transformation between right-handed B-DNA and left-handed Z-DNA. For duplexes of DNA with oligonucleotide analogs such as peptide nucleic acids (PNAs), less is known about the effects on structure such as the base pair twist and tilt parameters and handedness. However, in PNA:PNA duplexes, the absence of chiral information determining helical handedness allows the relationship between preferred helical handedness and structural design to be manipulated and, therefore, better understood. In this chapter, we report a protocol for switching between B- and Z-DNA:DNA duplexes, and the experimental procedures for obtaining right- or left-handed PNA:PNA duplexes.

Human experience informs us of the two extreme consequences of crowding: random behavior of the individuals, in which each takes a singular path; and cooperative behavior, in which the individuals in the crowd act in a predictable uniform manner, such as in a military organization These extremes find parallels in the crowded situations encountered at the molecular level, exemplified for the former by glassy states, such as often encountered in polymeric materials,1 or for the latter, in the uniform archetypal arrangements of crystals or liquid crystals. Here we review the cooperative characteristics of uniform arrangements that take a chiral form and explore how these characteristics lead to left- and right-handedness. These studies lead us to understand the basis of amplification of chirality in regular arrays, in which small influences have large consequences, and how chiral cooperativity acts in the resolution of conflict between influences favoring left- and right-handedness.2

Oligomers of PNA:PNA duplexes with different amino acids appended to one strand of each duplex have been synthesized and studied for their chiral optical properties. The terminal amino acid is known to affect both the handedness and amplitude of the CD signal from a given duplex. Here we have investigated an extended set of duplexes with several different amino acids appended, determining the CD, absorbance, and denaturation behavior of these chains in water and glycerol. Thermal unfolding profiles of the duplexes together with NMR data point to conformational heterogeneity as a function of amino acid, oligomer length, and solvent. The results suggest that the PNA:PNA double helix has access in solution to a dynamic ensemble of conformational states rather than a single dominant state. The conformational ensemble varies as a function of oligomer length according to the cooperative properties of the competing conformations of the double helix. A simplified statistical theoretical model allowing only two conformational states with distinct cooperative properties consistent with the denaturation results can account for much of the experimental data. This conformational heterogeneity in PNA duplexes is reflected in significantly greater flexibility of PNA:DNA duplexes relative to either DNA or RNA double helices. The results demonstrate that the principles of chiral cooperativity such as seen in the sergeants and soldiers and majority rule experiments must be altered when the structure of the system becomes a variable depending on the chiral information input.

Strong arguments can be found in the literature addressed to the question of the origin of homochirality in life, supporting the hypothesis that primordial life could have evolved in both homochiral forms and that early on when life was still rarely found, random events led to the survival of only one of these living mirror images. This proposal is an alternative to the generally accepted view that small enantiomeric excesses of biologically important molecules were amplified to homochirality prior to life's origin. Acceptance of the possibility of "two equal runners" leads to the importance of research investigations on routes to formation of ensembles of racemic mixtures of isotactic biologically interesting polymers, supramolecular entities and aggregates.

The signature characteristic of different kinds of polymers, synthetic and natural, is cooperativity arising from the recurring features common to all polymer structures. Cooperativity and amplification are simply different words expressing the same phenomenon leading one to expect that studies of polymers will allow small effects to be magnified, or, that is, for small effects to have surprisingly large effects on polymer proper-ties. In the work reviewed in this short article we see this amplification at work in two different ways: (1) a synthetic polymer that forms a helical conformation but without preference for helical sense, right or left handed, is caused to take on a large excess of a single helical sense by incorporation of chiral information in surprising ways, including by forming chiral centers by deuterium substitution; (2) two polymers that mix homogeneously with each other by virtue of an unknown attractive interaction are revealed by deuterium labeling to be involved in a weak hydrogen bond between a hydrogen bound to aromatic carbon and an ethereal oxygen. Copyright (c) 2007 John Wiley & Sons, Ltd.

Although all filamentous phages are constructed of chiral components, this study of eight of these phages (fd, IKe, I(2)2, X-2, Pf1, Pf3, tf-1, and X) shows that some form nematic liquid crystals, which are apparently oblivious to the chirality of the components, while others form cholesteric liquid crystals revealing a type of structural chirality not normally encountered. Additions of dopants that interact with the DNA or protein components of the viruses change the liquid crystal properties of seven of the phages. In these seven, DNA-capsid symmetry differences do not allow strict structural equivalency among the protein subunits. The polymorphism arising from this nonequivalency is proposed here to give rise to coiling of the filaments, a large-length-scale chirality that is responsible for forming cholesteric liquid crystal phases. Only one phage of those studied here, Pf1, which is distinguished from the others in its DNA-capsid interactions, forms nematic phases under all conditions tried. The formation of liquid crystals has been developed as a method to detect subtle overall shape effects arising from DNA-subunit-derived polymorphism, an unusual role for the mesogenic state and a new tool for the study of filamentous phage structure.