Developments in liquid-crystalline dimers and oligomers

ABSTRACT

Liquid-crystalline dimers and bimesogens have attracted much attention due to their propensity to exhibit the spontaneously chiral twist-bend mesophase (N_TB), most often by dimers with methylene spacers. Despite their relative ease of synthesis, the number of ether-linked twist-bend materials significantly lags behind those of methylene-linked compounds. In this work, we have prepared and studied a range of ether-linked bimesogens homologous in structure to the FFO9OCB; as with methylene-linked systems, it appears that it is molecular topology and the gross molecular shape that are the primary drivers for the formation of this phase of matter. Dimers and bimesogens are well studied within the context of the twist-bend phase; however, present understanding of this mesophase in oligomeric systems lags far behind. We report our recent efforts to prepare further examples of oligomeric twist-bend nematogens, including further examples of our ‘n+1’ methodology, which may allow the synthesis of high-purity, monodisperse materials of any given length to be prepared. We have observed that there is a tendency for these materials to exhibit highly ordered soft-crystalline mesophases as opposed to the twist-bend phase.     

TMDIM: an improved algorithm for the structure prediction of transmembrane domains of bitopic dimers

\(\alpha\)-Helical transmembrane proteins are the most important drug targets in rational drug development. However, solving the experimental structures of these proteins remains difficult, therefore computational methods to accurately and efficiently predict the structures are in great demand. We present an improved structure prediction method TMDIM based on Park et al. (Proteins 57:577–585, 2004) for predicting bitopic transmembrane protein dimers. Three major algorithmic improvements are introduction of the packing type classification, the multiple-condition decoy filtering, and the cluster-based candidate selection. In a test of predicting nine known bitopic dimers, approximately 78% of our predictions achieved a successful fit (RMSD <2.0 Å) and 78% of the cases are better predicted than the two other methods compared. Our method provides an alternative for modeling TM bitopic dimers of unknown structures for further computational studies. TMDIM is freely available on the web at https://cbbio.cis.umac.mo/TMDIM. Website is implemented in PHP, MySQL and Apache, with all major browsers supported.     

Antimicrobial activity of newly synthesized thienoquinolizidines derivatives: inspired by natural plant alkaloids

The antimicrobial activity of 16 newly prepared quinolizidines derivatives using bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Proteus sp., Escherichia coli) acid fast bacterium Mycobacterium smegmatis, yeasts (Candida albicans, Candida parapsilosis), and filamentous fungi (Fusarium culmorum, Microsporum gypseum, Aspergillus flavus, Botrytis cinerea, Alternaria alternata) was studied in this paper. The best antibacterial properties were demonstrated by derivatives 11Ba, trans10Bb and 11Bb, and the most sensitive microorganism was found to be the gram-positive bacterium S. epidermidis. The derivative 11Bb showed the best antifungal activity, while C. albicans was resistant to all tested derivatives, and C. parapsilosis was fully inhibited in the presence of the derivative 11Ba and 11Bb. Among the filamentous fungi, only the dermatophyte M. gypseum was partially inhibited. Biofilms represent the most prevalent type of microbial growth in nature and are crucial to the development of clinical infections. Newly synthesized derivatives were also added into the medium throughout the biofilm formation. We have observed a significant decrease of biofilm formation in the presence of quinolizidine derivatives, testifying to their significant antimicrobial activity. It seems that the relationship between antimicrobial activity and the structure is based on the alkaline character due to nitrogen, the saturated basic quinolizidine skeleton, and the position of sulfur in the molecule.     

Necessarily Incompatible Consistent Wants

This paper argues that the wants or desires of a person can be consistent with each other and still necessarily incompatible with each other and for interesting reasons. It is argued here that this problem is not rare and that there is no solution in sight.     

Determination of Volatile Organic Compounds by a Novel Polymer Spin-Coated Thin Film and Surface Plasmon Resonance

Here, the synthesis, characterization, and volatile organic compound (VOCs) sensing of a 1,3-dimethyl polyphenylene vinylene polymer is reported. The synthesis was performed by a Witting condensation through the reaction of 1,4-terphthaldehyde with the phosphonium chloride of meta-xylene. The material was characterized by infrared spectroscopy, elemental analysis, and thermogravimetric analyses. Thin films of the polymer were prepared by spin coating at speeds from 1000 to 5000?rpm. Ultraviolet–visible spectroscopy and surface plasmon resonance were used to characterize the spin-coated films. The thicknesses of the films were estimated by fitting the curves and were between 4.5 and 24.5?nm depending on the speed. The refractive index of the new polymer was 1.72. The polymer spin-coated films were exposed to volatile organic vapors to characterize their sensing properties by surface plasmon resonance as a function of time. The results showed that the new material responded rapidly, sensitively, and reversibly to VOCs.     

Formation of tricyclo[6.3.0.02,5]undecane derivatives during attempts to make the rumphellatin A–C oxacarbon skeleton

The results of several approaches to make the 4,4,8-trimethyl-12-oxatricyclo[7.2.1.0^2,5]dodecane motif present in rumphellatins A–C are reported. The strategy adopted involved (9E)-12,12-dimethyl-5-oxatricyclo[8.2.0.0^4,6]dodec-9-en-11-ol as an intermediate, but when attempts were made to connect the third methyl group to the carbon skeleton by reacting the epoxide with MeLi under boron-trifluoride catalysis, an unprecedented transannular reaction occurred. The desired product was not formed; instead, compounds containing a tricyclo[6.3.0.0^2,5]undecane moiety were obtained, in one case in better than 70% yield.     

Synthesis of heterocycles from arylacetonitriles: Powerful tools for medicinal chemists

Arylacetonitriles are versatile building blocks for the construction of heterocyclic scaffolds in medicinal chemistry. These intermediates are able to engage in a variety of synthetic transformations, giving rise to diverse biologically active structures. This digest focuses on recent applications of this synthetic methodology by drug discovery teams across several disease areas, with an emphasis on different reaction types.     

Ionization Constants of DL-2-Aminobutyric Acid and DL-Norvaline Under Hydrothermal Conditions by UV–Visible Spectroscopy

The first and second ionization constants for the amino acids DL-2-aminobutyric acid (DL-2-aminobutanoic acid) and DL-norvaline (DL-2-aminopentanoic acid) were determined under hydrothermal conditions, from 175 to 275 °C at 10 MPa, using thermally-stable colorimetric pH indicators (acridine, 4-nitrophenol and 2-naphthoic acid). The measurements were carried out by UV–visible spectroscopy using a high-temperature, high-pressure platinum flow cell with sapphire windows, which minimized the effects of thermal decomposition. The results were combined with literature values from titration calorimetry at 25–130 °C to yield an extended van’t Hoff model for the temperature dependence of the ionization constants for the carboxylic acid and ammonium groups, \( K_{\text{a,COOH}} \) and \( K_{{{\text{a,NH}}_{3}^{ + } }} \), over the entire temperature range. The experimental results for the second ionization constant \( K_{{{\text{a,NH}}_{3}^{ + } }} \) at elevated temperatures are consistent with the predictions from the Yezdimer–Sedlbauer–Wood functional group additivity model, but for the first ionization constant \( K_{\text{a,COOH}} \) are not. This suggests that the group contribution parameters for the standard partial molar heat capacity of the carboxylic acid group are in error, or that nearest neighbor interactions between the –COOH and \( - {\text{NH}}_{3}^{ + } \) groups cause a breakdown in the functional group additivity relationship.     

Calculating approximation guarantees for partial set cover of pairs

As a part of a heuristic for the fast detection of new word combinations in text streams, we consider the NP-hard Partial Set Cover of Pairs problem. There we wish to cover a maximum number of pairs of elements by a prescribed number of sets from a given set family. While the approximation ratio of the greedy algorithm for the classic Partial Set Cover problem is completely understood, the same question for covering of pairs is intrinsically more complicated, since the pairs insert some graph-theoretic structure. The best approximation guarantee for the first greedy step can be rephrased as a problem in extremal combinatorics: Assume that we may place a fixed number of subsets of fixed and equal size in a set, how many different pairs of elements can we cover? In this paper we introduce a method to calculate optimal approximation guarantees, and we demonstrate its use on the smallest set families.