On the Chiroptical Behavior of Conjugated Multichromophoric Compounds of a New Pseudoaromatic Class: Bicolchicides and Biisocolchicides

It is well known that, stemming from the mutual interplay between chromophores, circular dichroism (CD) is a powerful technique to deal with structural problems for both the small organic molecule and the biopolymer. However, quantitative interpretations of the spectroscopic and structural terms that give rise to the exciton couplet are usually presented for ideal cases, or a few CD bands only are taken into account, overlooking the role of the solvent medium. Circular dichroism and UV absorption spectra were carried out for colchicide (3) and isocolchicide (6), as well as their coupling products, 10,10'-bicolchicide (2) and 9,9'-biisocolchicide (5), in both hydrogen bonding and non hydrogen bonding solvents, as well as MeCN/H(2)O mixtures. A dramatic control by the solvent emerged, as even tiny changes in the composition of solvent mixtures, at ca 1 water molar fraction, induced a dramatic modification of their CD bands. A mutarotation phenomenon--long known for isocolchicine (8)--was also observed for 5, and can be attributed to the interconversion between atropisomers (R(a),7S),(R(a),7'S)-5a and (R(a),7S),(S(a),7'S)-5b. Our data show that with molecules built on two structurally identical moieties which embody both hydrophilic and hydrophobic groups, even tiny changes in the composition of solvent mixtures cause a dramatic modification of the CD bands. Their analysis arrives at a qualitative rationalization of the observed CD couplets from the coupling of high energy transitions, while attempts at a quantitative interpretation of these phenomena through time-dependent density functional theory allowed to reproduce satisfactorily the CD spectrum in the 300-450 nm region only. Failure with higher energies probably reflects currently inadequate specific theoretical treatments of the solvent medium

Structural characterization of an ionic liquid in bulk and in nano-confined environment using data from MD simulations

This article contains data on structural characterization of the [C2Mim][NTf2] in bulk and in nano-confined environment obtained using MD simulations. These data supplement those presented in the paper “Insights from Molecular Dynamics Simulations on Structural Organization and Diffusive Dynamics of an Ionic Liquid at Solid and Vacuum Interfaces” [1], where force fields with three different charge methods and three charge scaling factors were used for the analysis of the IL in the bulk, at the interface with the vacuum and the IL film in the contact with a hydroxylated alumina surface. Here, we present details on the construction of the model systems in an extended detailed methods section. Furthermore, for best parametrization, structural and dynamic properties of IL in different environment are studied with certain features presented herein

Theoretical and experimental investigations

To what extent are transannular reactions of medium-ring compounds are dependent on their conformations and to what extent can reaction conditions and other factors such as ring size and substituents partially or completely control the transannular interaction? These questions have been investigated with experimental and theoretical studies in this work. A comprehensive study of hemiacetal formation and 1,x-hydride shift (x = 4 – 6) has been carried out for model compounds 1 – 5 in order to elucidate the influence of different factors such as ring size, presence of a C=C double bond and substituents on these transannular reactions. ... The theoretical and NMR investigations on 1 – 3 indicate that the eight-membered disubstituted compounds present the optimal conditions for the ‘contact’ of substituents in the positions 1 and 5 for the transannular interactions resulting in transannular products. The X-ray crystal structures have clearly shown that compounds 1 and 3 exist as hemiacetals. The experiments clearly indicate highly dynamic behaviour of these molecules and the existence of equilibrium between tautomers especially in protic solvents, i.e., DMSO-d6 and D2O, which have not been reported before. The tautomeric equilibrium between 1 and its transannular product drives in the direction of hemiacetal in a range of polar and non-polar solvents. But remarkably, the combined effect of solvent polarity and temperature drives the equilibrium in the reverse direction to a significant extent. The equilibrium constant Keq for forward reaction is reduced to 16.5 in DMSO-d6 at 403 K and 31.3 in D2O at 323 K. In the case of 2, the transannular hemiacetal is only ≤1 % in D2O at higher temperature. In contrast, in compound 3 the hemiacetal is favoured exclusively in benzene-d6 at 298 and 343 K. The experimental findings for the tautomeric equilibrium of compounds 1 – 5 are substantiated by theoretical investigations. The present results represent the first comparison of transannular hemiacetal formation as a function of conformation in eight- and ten-membered hydroxy-ketones. Since these compounds possess very complex multidimensional potential energy hypersurfaces (PEHS), the choice of good starting geometries for these molecules was facilitated by applying molecular mechanics. The starting geometries referred as preferred starting conformer are selected on the basis of factors such as proximity of the reacting groups and energetics. Detailed conformational and energetic investigations carried out using DFT theory shows that the preferred starting conformer of 1, 4 and 5 are 8.5, 8.6 and 8.1 kcal mol-1, respectively, less stable than the corresponding hemiacetals in the gas phase. It implies thermodynamically preferred products in 1, 4 and are 1a, 4a and 5a. In case of 2 and 3 the preferred starting conformers are only 3.6 and 4.6 kcal mol-1 less stable that the corresponding hemiacetals. The calculated (B3LYP/6-31+G*) activation barriers for hemiacetal formation in 1, 2, 3, 4 and 5 are 38.2, 35.2, 36.5, 38.2 and 36.9 kcal mol-1, respectively, in the gas phase. The transannular hemiacetal formation occurs through a four-membered cyclic transition-state which is most tight in 2. The activation barriers calculated using continuum solvation models (PCM) were not significantly different from the gas phase calculations. It is obvious that the theoretical models used are not able to handle specific solvent effects, so we consider results obtained for hemiacetal formation in water and chloroform semiquantitatively. The experimental data show that the transannular 1,5-hydride shift is catalysed both by base and acid. A comparative theoretical study of the transannular 1,4-, 1,5- and 1,6-hydride shifts in compounds 1, 2, 4 and 5 shows consensus with the experimental findings that the presence of a metal counterion or acid lowers the activation barriers. In all cases, the reaction proceeds through a hexagonal transitionstate structure. The calculated (B3LYP/6-31+G*) activation barriers for 1,5-, 1,4- and 1,6-hydride shift in compounds 1, 2, 4 and 5 are 46.6, 52.2, 43.0 and 28.0 kcal mol-1, respectively, for the uncatalysed reaction. One of the key results is that the activation barriers for 1,6-hydride shift in 5 (28.0 kcal mol-1) and the corresponding intermolecular hydride shift (26.4 kcal mol-1) in the methanol and formaldehyde model system are very similar in the uncatalysed reactions. Moreover, the characteristics of the six-membered cycle formed in transition-state structure of 1,6-hydride shift is similar to the six-membered cycle formed in the intermolecular hydride shift between formaldehyde and methanol. The potential energy profiles for the degenerate 1,4-, 1,5- and 1,6-hydride shifts correspond to the two interchanging hydroxy-ketones and a high lying unsymmetrical transition structure for interconversion of 2 and 6, respectively and symmetrical transition structures for interconversion of 1 and 4, respectively. In the presence of a metal counterion, the transannular 1,6-hydride shift and the intermolecular hydride shift took place via low energy complexes. The low energy complexes are formed by the electrostatic attraction of metal counterion with carbonyl oxygen atom. It is highly likely that similar intermediates are involved in 1,4- and 1,5-hydride shifts too, but attempts to locate similar low energy complexes in 1, 2 and 4 all failed. The transition-state formed in the acid catalysed reaction in 5 can best be described as a localised C-H-bridged cation with a facile 1,6-hydride shift. The transition-states for the transannular hemiacetal formation and 1,x-hydride shift are likely to closely resemble the preferred starting conformer. Thus, it might be anticipated that knowledge of the preferred starting conformations would be of great predictive value in determining the type of reaction systems 1 – 5 undergo. For the first time the synthetic potential of transannular 1,5-hydride shift in preparing keto-ethers by reaction of 1 with alcohols in presence of 0.04 M HCl is investigated. This method is attractive for the reasons that it is unexpensive and the hydroxy group can be easily deprotected. However, a major limitation of this method is that the yield of keto-ether of 1 with alcohols such as methanol and ethanol is low. On the other hand, reactions with alcohols such as 2-bromobenzyl alcohol give good yields of the keto-ether. The transannular reactions in hydroxy-ketones reported in the present study seem to serve as good models, in terms of electronic structure and geometry, for the transition-state of transannular hemiacetal formation and hydride shift reactions in medium-ring compounds. Our results suggest that such reactions, particularly hydride shift, can be exploited via easy protection and deprotection of hydroxy groups in the synthesis of important target molecule. Thus, the underlying chemistry of transannular reactions in certain medium-rings reasonably offers potential as a strategic element in the synthesis of polycyclic natural products. It is anticipated that the knowledge obtained in these experiments can be fruitfully applied to the goals for the synthesis of medium rings and the chemistry related to these experiments

Ruthenium-catalyzed azide alkyne cycloaddition reaction: scope, mechanism and applications

The ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) affords 1,5-disubstituted 1,2,3-triazoles in one step and complements the more established copper-catalyzed reaction providing the 1,4-isomer. The RuAAC reaction has quickly found its way into the organic chemistry toolbox and found applications in many different areas, such as medicinal chemistry, polymer synthesis, organocatalysis, supramolecular chemistry, and the construction of electronic devices. This Review discusses the mechanism, scope, and applications of the RuAAC reaction, covering the literature from the last 10 years

Semiconducting Polymers and Block Copolymers Prepared by Chain-Growth Living Polymerization

Organic semiconducting polymers are the unique materials that considered a basis for the next generation of electronic and optoelectronic applications. However, high device performance of semiconducting polymers strongly depends on their molecular structure and nanoscale organization. Therefore, it is an essential task to develop robust and versatile synthetic approaches to build such well-defined semiconducting polymer materials. This Ph.D. study aimed at design of state-of-the-art synthetic approaches towards organic semiconducting polymers via chain-growth living polymerization as well as development of polymer architectures which can self-organize into supramolecular nanoassemblies or allow external control of the polymer’s properties. First, we prepared a series of temperature-responsive water-soluble poly(N-isopropylacrylamide)-functionalized polythiophenes, and showed that their supramolecular organization and temperature control of their conformation and conjugation length was strongly dependent on the extent of regioregularity of the polythiophene backbone. In order to improve the regioregularity, we developed a general approach to highly efficient external catalytic initiators for the synthesis of various semiconducting polymers. Extensive studies allowed better understanding of the unusual catalytic systems, and their behavior in chain-growth living polymerization reactions. Using this approach, we synthesized a variety of amphiphilic polythiophene block copolymers incorporating a low energy gap perylenedicarboximide (PDCI) unit to demonstrate the possibility to control supramolecular organization and photophysical properties of such systems by using external stimuli (such as solvent and temperature). As part of our general studies towards design of near-infrared (NIR) fluorescent conjugated polymers, we developed a synthetic approach to a novel class of such materials which are based on cyanine dyes as monomeric repeating units. The obtained polymers showed a variety of properties (thermal stability, solubility, absorption and fluorescence in the NIR range) that may make them a useful class of NIR fluorescent conjugated polymers

Non-empirical molecular orbital calculations related to aromatic and heteroaromatic systems

A large program of ab initio MO studies of conjugated molecules has been completed. A major point of interest was the molecular geometry in a number of planar and non-planar cases. The method was first applied to small molecules of known geometry, and then to large systems including cyclo-octatetraene, the longer annulenes, and various 7- and 9- membered ring heterocycles

Synthesis and Characterization of Poly(9,9-Dihexylfluorene-mb-methylene)s

The synthesis and characterization of copolymers possessing exact repeating sequences of 9,9-dihexylfluorene and methylene repeat units are described. Each poly(9,9-dihexylfluorene-mb-methylene) (PFM, mb = multiblock) was synthesized following the assembly of a symmetrically disubstituted monodisperse oligofluorene. Alkyl segments possessing terminal alkene functionality were then coupled at both of the substituted positions on the oligofluorene to give a macromolecular "segmer" compound. Each segmer was polymerized using Acyclic Diene Metathesis (ADMET) and, following post-polymerization hydrogenation, a PFM with an entirely repeating diblock sequence was produced. PFMs possessing 9,9-dihexylfluorene segment lengths of x = 1, 2, 3, 4, 7, or 8 units and methylene segment lengths of y = 10 or 18 units were prepared to give a ten member PFM library. As PFMs have exact chemical compositions and monomer unit sequencing, studies aimed at elucidating solution and bulk phase trends were performed. Spectroscopic characteristics that make polyfluorene-type materials attractive include their generally efficient blue light emission (λmax ~ 448 nm). Successful investigations into the optical tuning of PFMs in solution and in the bulk are described. Additionally, thermal- and photostabilities of PFMs under a variety of conditions are reported and compared to the related homopolymer, poly(9,9-dihexylfluorene) [PDHF]. Compared to PDHF, PFMs display similar, and in some cases superior resistance to photobleaching processes. Additionally, thermal and photostability investigations into keto-induced degradation processes of PFMs suggest that interruption of the fluorene segments with alkyl spacers effectively suppresses intrachain charge migration and interchain Förster energy transfer in the bulk. The rate of PFM, and likewise PDHF degradation was found to be at least partially dependent on the initial state of the sample.Efforts toward the transition metal-catalyzed production of cyclic oligomers are described. Two rigid bifunctional molecules bearing both transition-metal metathesis initiating and terminating groups were prepared. The synthesis and metathesis activity of these compounds are reported