Roman Bielski

Mechanical resolution of chiral objects in achiral media: where is the size limit?

Macroscopic chiral objects (boats and planes with turned rudders, shoes, etc.) get separated from their mirror-image counterparts by motion in achiral media. However, chiral molecules are not enantio-differentiated without the presence of a chiral environment, which may be due to other chiral molecules in the medium. This article explores the reasons of this micro/macro difference as well as the size borderline between the two regimes. There are two major demarcation lines, both related to the objects chaotic thermal motion. The first one is due to destruction of the necessary spatial orientation by the fast rotational diffusion. Only particles larger than 1 μm can maintain their original orientation for 1 sec or longer. For smaller particles, an additional external orienting factor, e.g., a strong electric field has to be applied. The second limitation is defined by the ratio of the hydrodynamic separation of the enantiomers (which is directly proportional to time) to their displacement due to the translational Brownian motion (which is proportional to square root of time). On the laboratory time scales (up to a year), the chiral objects have to be larger than 0.25 μm to be resolved. On evolutionary time scales, much smaller object could be resolved. For enantiomers approaching the molecular size, periods comparable to the age of the universe would be required.

The induction of oxidative stress in cervix carcinoma cells by levoglucosenone derived 4-S-salicyl derivative and (1–4)-S-thio-disaccharides. Part 4

(1-4)-S-thiodisaccharides were shown to kill various cancer cell lines, including cervix, lung, mammary-gland and colon by unknown mechanisms. Here we identified two actions of levoglucosenone derived (1-4)-S-thiodisaccharides against cervix cancer cells: induction of oxidative stress and DNA damage. In consequence, (1-4)-S-thiodisaccharides lowered the cellular GSH level and changed the expression profile of genes encoding key proteins involved with oxidative stress response. We also observed that (1-4)-S-thiodisaccharides induced DNA damage and interfered with the thioredoxin (Trx) system. Both actions, as induced by FPC6, were stronger when dihedral angles of sulfur bridge were set to 110°, 100° and 109°, clearly indicating differences when compared to FPC8. These findings demonstrate that the 1-4-thio bridge of disaccharide is a powerful anticancer pharmacophore, and its potential use needs further studies.

A Comment on “Separation of Chiral Molecules: A Way to Homochirality”

Keywords Chiral.Homochirality.Enantioselectiveseparation.Brownianmotion.Macroscopicandmicroscopicobjects.Resolution.Pre-biotic.HydrodynamicIn a recent paper Atencio (2012) proposes a mechanism which in the author’s mind could beresponsible for a pre-biotic separation of chiral molecules in the absence of a chiralenvironment. The author provides a thorough hydrodynamic analysis of particle separationin an aquifer based on their chirality. Without getting into the details of this analysis, weassume that it is correct. However, we think that the author fell into a trap by not consideringfundamental behavioural differences between different types of objects related to their sizescale.Mechanical and hydrodynamic separation of macroscopic chiral object in achiral media isan everyday occurrence, as everyone who watches sleigh rides on a hill or a sailing boatturning knows. The phenomenon, observed also in nature by (Nagle 1967, Welch 1998) wassubjected to theoretical analysis (de Gennes 1999, Howard et al. 1976) and even patented(Hirschfelder et al. 1977).The critical aspect here, not taken into account by Atencio (2012), is the effects of therandom thermal motions differentiating between the macro- and micro- scale chiral objects.This effect is negligible with the former but not with latter. De Gennes (1999) estimated theregime transition size to be ca. 1 μm. More detailed considerations of the effect of two kindsof random motion (Brownian motion and rotational diffusion) on the efficiency of hydro-dynamic resolution as a function of the object’s size (Tencer and Bielski 2011) showed thatrotational diffusion destroys the object’s spatial orientation necessary for the hydrodynamicdifferentiation and only objects larger than 1 μm can maintain such orientation longer than1 s, in agreement with de Gennes (1999) estimate. Even if the orientation can be maintained

Recognition of Thiols in Coupling Reactions to Organic and Carbohydrate Acceptors

Reactions of thiols in thio-click coupling processes with various reactive systems (including carbohydrates) are compiled. A selection of simple and complex thiols in stereoselective and non-stereoselective approaches recognizing their reactivity is also reviewed. Solvents, employed in the discussed processes including water, are briefly discussed as well.

Example of Sacrificial Unit Using Two Different Click Reactions in Coupling and Decoupling (CAD) Chemistry

An example of a specific coupling and decoupling (CAD) chemistry is described. It takes advantage of propargyl acrylate as a sacrificial unit (SU). The addition of a selected compound representing a molecular unit equipped with an azide functionality to the terminal triple bond of the SU and another compound acting as a molecular unit equipped with a thiol functionality to the conjugated double bond of the SU proceeded at very good yields. The construct containing two molecular units can be decoupled using a few different reactions and the decoupling can take place at two positions.

Recent examples of novel synthetic approaches to diverse amino sugars

This brief review discusses selected syntheses of amino sugars published in this century. The specific examples are divided into categories based on the location of the amino group in the final product. The review puts emphasis on diastereoselectivity and enantioselectivity effects. It considers mechanisms of the reactions introducing the amino group and applications of synthesized amino products. Potential and already implemented medical applications of presented compounds are also highlighted.

Domino and Intramolecular Rearrangement Reactions as Advanced Synthetic Methods in Glycoscience: Witczak/Domino

Reactions as Advanced Synthetic Methods in Glycoscience Edited by Zbigniew J. Witczak and Roman Bielski QP702.G577 D66 2016 Each chapter in this book is written by experts in the fields of domino reactions or intramolecular rearrangements and describes their current research. Although many recently isolated carbohydrates fulfill various sophisticated functions, their structures are often very complex. Domino reactions and intramolecular rearrangements offer an elegant and convenient approach to the synthesis of many complex molecules, which are normally difficult to synthesize via alternative routes.