Center for Molecular Modeling - SBO POXPEG B/13515/*

Synthesis of poly(2-oxazoline)s with side chain methyl ester functionalities: Detailed understanding of copolymerization behavior of methyl ester containing monomers with 2-alkyl-2-oxazolines

michel — Mon, 23 Mar 2015 09:25:40 +0000

P. Bouten, D. Hertsen, M. Vergaelen, B. Monnery, S. Catak, J. van Hest, V. Van Speybroeck, R. Hoogenboom

Journal of Polymer Science Part A: Polymer Chemistry

7 (17), 2711-2719

2015

Abstract

Poly(2-oxazoline)s with methyl ester functionalized side chains are interesting as they can undergo a direct amidation reaction or can be hydrolyzed to the carboxylic acid, making them versatile functional polymers for conjugation. In this work, detailed studies on the homo- and copolymerization kinetics of two methyl ester functionalized 2-oxazoline monomers with 2-methyl-2-oxazoline, 2-ethyl-2-oxazoline, and 2-n-propyl-2-oxazoline are reported. The homopolymerization of the methyl ester functionalized monomers is found to be faster compared to the alkyl monomers, while copolymerization unexpectedly reveals that the methyl ester containing monomers significantly accelerate the polymerization. A computational study confirms that methyl ester groups increase the electrophilicity of the living chain end, even if they are not directly attached to the terminal residue. Moreover, the electrophilicity of the living chain end is found to be more important than the nucleophilicity of the monomer in determining the rate of propagation. However, the monomer nucleophilicity can be correlated with the different rates of incorporation when two monomers compete for the same chain end, that is, in copolymerizations. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015

DOI

http://dx.doi.org/10.1002/pola.27733

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15_JPolymerScienceA_xxxx_Bouten.pdf

On the Possibility of [1,5] Sigmatropic Shifts in Bicyclo[4.2.0]octa-2,4-dienes

michel — Sun, 30 Nov 2014 13:27:40 +0000

H. Goossens, J.M. Winne, S. Wouters, L. Hermosilla, P. J. De Clercq, M. Waroquier, V. Van Speybroeck, S. Catak

Journal of Organic Chemistry

80 (5) 2609-2620

2015

Abstract

The thermal equilibration of the methyl esters of endiandric acids D and E was subject to a computational study. An electrocyclic pathway via an electrocyclic ring opening followed by a ring flip and a subsequent electrocyclization proposed by Nicolaou [Chem. Soc. Rev. 2009], was computationally explored. The free energy barrier for this electrocyclic route was shown to be very close to the bicyclo[4.2.0]octa-2,4-diene reported by Huisgen [Tet. Lett. 1968]. Furthermore, the possibility of a [1,5] sigmatropic alkyl group shift of bicyclo[4.2.0]octa-2,4-diene systems at high temperatures was explored in a combined computational and experimental study. Calculated reaction barriers for a biradical-mediated stepwise [1,5] sigmatropic alkyl group shift were shown to be comparable with the reaction barriers for the bicyclo[4.1.0]hepta-2,4-diene (norcaradiene) walk rearrangement, whereas calculated reaction barriers for a concerted [1,5] sigmatropic alkyl group shift were found to be higher in energy. However, the stepwise pathway is suggested to only be feasible for appropriately substituted compounds. Experiments conducted on a deuterated analogous diol derivative confirmed the calculated (large) differences in barriers between electrocyclic and sigmatropic pathways.

DOI

http://dx.doi.org/10.1021/jo5027639

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15_JOC_xxxx_HGoossens.pdf

Elucidating the Structural Isomerism of Fluorescent Strigolactone Analogue CISA-1

lore — Tue, 25 Nov 2014 13:44:51 +0000

H. Goossens, T.S.A Heugebaert, B. Dereli, M. Van Overtveldt, O. Karahan, I. Doğan, M. Waroquier, V. Van Speybroeck, V. Aviyente, S. Catak, C.V. Stevens

European Journal of Organic Chemistry

2015 (6), 1211–1217

2015

Abstract

The synthesis of a new potent strigolactone analogue (CISA-1), resulting in the formation of two interconverting structural isomers, which could not be identified, was recently reported by Rasmussen et al [Molecular Plant, 2013, 6, 100]. In the present study, a combined computational and experimental approach is used to identify the exact nature of these structural isomers. While standard experimental techniques were not able to determine the identity of the isomers, chromatographic methods excluded E/Z isomerisation. Computational 1H NMR chemical shift values and DFT calculations on interconversion barriers strongly suggest that the CISA-1 isomers were interconverting (Z)-configured atropisomers.

DOI

http://dx.doi.org/10.1002/ejoc.201403457

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15_EurJOC_xxxx_HGoossens.pdf

15_EurJOC_2015(6)_1211_HGoossens.pdf

Accelerated living cationic ring-opening polymerization of a methyl ester functionalized 2-oxazoline monomer

dietmar — Wed, 19 Nov 2014 15:41:28 +0000

P.J.M. Bouten, D. Hertsen, M. Vergaelen, B. Monnery, M.A. Boerman, H. Goossens, S. Catak, J.C.M. van Hest, V. Van Speybroeck, R. Hoogenboom

Polymer Chemistry

6, 514-518

2015

Abstract

Kinetic studies on the homo- and copolymerization of 2-methoxycarboxyethyl-2-oxazoline (MestOx) with 2-methyl-2-oxazoline (MeOx) and 2-ethyl-2-oxazoline (EtOx) were performed. For the homopolymerisation of MestOx an increased propagation rate constant was observed compared to MeOx and EtOx while the copolymerization of MestOx with MeOx or EtOx unexpectedly revealed slower incorporation of MestOx. Density functional theory (DFT) calculations show that nearby MestOx residues in the living chain can activate both the oxazolinium chain end and the attacking monomer, stabilizing the propagation transition state, leading to faster homopolymerisation of MestOx. These effects also accelerate incorporation of both monomers in the copolymerisations. However, since MeOx is shown to be more nucleophilic than MestOx, the incorporation order is reversed in the copolymerisations.

Open Access version available at UGent repository

DOI

http://dx.doi.org/10.1039/C4PY01373E

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14_Polym-Chem_2015_6_514_Bouten.pdf

Triazolinediones enabling ultrafast and reversible click chemistry for facile design of healable and reshapable polymers

michel — Fri, 27 Jun 2014 13:56:44 +0000

S. Billiet, K. De Bruycker, F. Driessen, H. Goossens, V. Van Speybroeck, J. Winne, F. Du Prez

Nature Chemistry

6 (9), 815-821

2014

Abstract

With its focus on synthetic reactions that are highly specific and reliable, ‘click’ chemistry has become a valuable tool for many scientific research areas and applications. Combining the modular, covalently bonded nature of click-chemistry linkages with an ability to reverse these linkages and reuse the constituent reactants in another click reaction, however, is a feature that is not found in most click reactions. Here we show that triazolinedione compounds can be used in click-chemistry applications. We present examples of simple and ultrafast macromolecular functionalization, polymer–polymer linking and polymer crosslinking under ambient conditions without the need for a catalyst. Moreover, when triazolinediones are combined with indole reaction partners, the reverse reaction can also be induced at elevated temperatures, and the triazolinedione reacted with a different reaction partner, reversibly or irreversibly dependent on its exact nature. We have used this ‘transclick’ reaction to introduce thermoreversible links into polyurethane and polymethacrylate materials, which allows dynamic polymer-network healing, reshaping and recycling.

DOI

http://dx.doi.org/10.1038/nchem.2023

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14_NatureChemistry_6(9)815_Billiet.pdf

Dynamics of poly(2-oxazoline)s

dietmar — Mon, 17 Nov 2014 09:56:21 +0000

Description

Poly(2-oxazoline)s (POx) are an interesting class of biocompatible polyamides whose physical and chemical properties can easily be tuned. These polymers are readily synthesized via cationic ring-opening polymerization (CROP) of various monomers, yielding polymers with distinct properties. The characteristics of the resulting pseudo-polypeptides can be altered even further by chemical functionalization of the residue side chains. Because of their versatility and biocompatibility, poly(2-oxazoline)s are candidate drug-delivery systems, providing a viable alternative to the gold standard in this field, polyethylene glycol (PEG). Their polymerization is still a bottleneck, however, and more computational efforts should be directed toward it.

The CROP rate is highly dependent on the monomer side chain and this effect has been successfully modeled by static ab initio calculations. Since the effects at play are localized, model systems typically only include the last residue of the living polymer chain and the attacking monomer. However, our recent study of monomers with flexible, polar side chains, e.g. 2-methoxycarboxy-2-oxazoline (MestOx), has shown that nearby residues in the polymer chain are able to stabilize the CROP transition state (unpublished results). The size of the conformational space which has to be sampled to understand these interactions warrants a molecular dynamics (MD) approach.

In vivo, POx chains are involved in a complex equilibrium between hydration, intra- and intermolecular aggregation. The influence of different monomers on these phenomena is poorly understood, although they are the basis of clinically relevant supermolecular effects like micellation. Again, MD is the computational method of choice, since these effects are inherently dynamic.

Budget/project

SBO POXPEG B/13515/*, FWO A. Ghysels B/11335/*

Period

Saturday, 1 November, 2014 to Thursday, 30 April, 2015

Node days

2 900.00 days

Users

D. Hertsen, H. Goossens

Remaining days

2 900.00 days

Downloads

tier1-application-sep2014-dietmarhertsen.pdf

2014-034 4204354650 Hercules.pdf

TIER1 reference n°

2014-034

Status

Approved

WATOC 2014

wim — Thu, 25 Sep 2014 12:47:25 +0000

Santiago de Chile, Chile

Sunday, 5 October, 2014 to Friday, 10 October, 2014

Participant(s)

T. De Meyer, T. Verstraelen, A. Ghysels, H. Goossens, L. Joos, M. Waroquier

Project ref.

BOF mandaat, FWO mandaat, IAP VII P7/05 B/12909/*, SBO POXPEG B/13515/*

Conference reference

WATOC 2014

AMBER Workshop 2014

wim — Wed, 28 May 2014 06:30:13 +0000

Barcelona, Spain

Monday, 2 June, 2014 to Friday, 6 June, 2014

Participant(s)

D. Hertsen

Project ref.

SBO POXPEG B/13515/*

Conference reference

AMBER Workshop 2014

ChemCYS

wim — Thu, 27 Feb 2014 08:41:32 +0000

Blankenberge, Belgium

Thursday, 27 February, 2014 to Friday, 28 February, 2014

Participant(s)

J. Hajek, D. Hertsen, T. De Meyer, K. Hemelsoet

Project ref.

FWO MOFs (3G048612) B/12561/*, SBO POXPEG B/13515/*, BOF mandaat, FWO mandaat

Conference reference

ChemCYS

MOLSIM tutorial

wim — Thu, 09 Jan 2014 12:53:55 +0000

Amsterdam, The Netherlands

Sunday, 5 January, 2014 to Friday, 17 January, 2014

Participant(s)

D. Hertsen, J. Hajek, K. Hendrickx

Project ref.

FWO MOFs (3G048612) B/12561/*, SBO POXPEG B/13515/*, ERC KINPOR B/10761/*

Conference reference

MOLSIM 2014