uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Blom, Magnus
Publications (8 of 8) Show all publications
Olsson, S. K., Schäfer, C., Blom, M. & Gogoll, A. (2018). Exciton-Coupled Circular Dichroism Characterization of Monotopically Binding Guests in Host-Guest Complexes with a Bis(zinc porphyrin) Tweezer. ChemPlusChem, 83, 1169-1178
Open this publication in new window or tab >>Exciton-Coupled Circular Dichroism Characterization of Monotopically Binding Guests in Host-Guest Complexes with a Bis(zinc porphyrin) Tweezer
2018 (English)In: ChemPlusChem, ISSN 2192-6506, Vol. 83, p. 1169-1178Article in journal (Refereed) Published
Abstract [en]

A stiff-stilbene-linked bisporphyrin tweezer with inherent helicity was used for exciton-coupled circular dichroism (ECCD) characterization of a series of monotopically binding amine guest molecules. CD signals were observed for a variety of monoamines at relatively low tweezer/amine (host/guest) ratios between 1 :10 to 1: 70. For the amines producing the most intense CD signals, a binding stoichiometry of 1:2 was found. A likely explanation is the presence of guest-guest interactions in the complexes. This is supported by the correlation observed between CD signal intensity and magnitude of possible noncovalent binding between the guests, which can be divided into three groups showing no, moderate and strong response, respectively. Further support for this rationalization comes from molecular modelling.

Place, publisher, year, edition, pages
Weinheim: Wiley-VCH Verlagsgesellschaft, 2018
Keywords
bis-porphyrin tweezers, conformation analysis, exciton-coupled circular dichroism, host-guest systems, molecular modeling
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-371629 (URN)10.1002/cplu.201800564 (DOI)000454527200013 ()
Funder
Swedish Research Council, 621-2012-3379Carl Tryggers foundation , CTS 16 : 156
Available from: 2018-12-21 Created: 2018-12-21 Last updated: 2019-04-23Bibliographically approved
Blom, M., Norrehed, S., Andersson, C.-H., Huang, H., Light, M. E., Bergquist, J., . . . Gogoll, A. (2016). Synthesis and Properties of Bis-Porphyrin Molecular Tweezers: Effects of Spacer Flexibility on Binding and Supramolecular Chirogenesis. Molecules, 21(1)
Open this publication in new window or tab >>Synthesis and Properties of Bis-Porphyrin Molecular Tweezers: Effects of Spacer Flexibility on Binding and Supramolecular Chirogenesis
Show others...
2016 (English)In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 21, no 1Article in journal (Refereed) Published
Abstract [en]

Abstract: Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar ene-diyne (1), the helical stiff stilbene (2), or the semirigid glycoluril motif fused to  the porphyrins (3) are compared. Binding constants Ka = 10^4 to 10^6 M^-1 reveal subtle  differences between these tweezers, that are discussed in terms of porphyrin dislocation  modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen  guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis.

Keywords
Bisporphyrin tweezers, metalloporphyrins, porphyrinoids, host-guest chemistry, supramolecular chemistry, chirogenesis, chirality transfer, exciton coupled circular dichroism, conformational analysis
National Category
Organic Chemistry Engineering and Technology
Research subject
Chemistry with specialization in Organic Chemistry; Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-267826 (URN)10.3390/molecules21010016 (DOI)000369485600001 ()
Funder
Swedish Research Council, 621-2012-3379Swedish Research Council, 621-2011-4423
Available from: 2015-11-27 Created: 2015-11-27 Last updated: 2017-12-01Bibliographically approved
Blom, M. (2015). Light-Triggered Conformational Switches for Modulation of Molecular Recognition: Applications for Peptidomimetics and Supramolecular Systems. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Light-Triggered Conformational Switches for Modulation of Molecular Recognition: Applications for Peptidomimetics and Supramolecular Systems
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The main focus of this thesis is on photochemical modulation of molecular recognition in various host-guest systems. This involves the design, synthesis and integration of light-triggered conformational switches into peptidomimetic guests and molecular tweezer hosts. The impact of the switches on guest and host structures has been assessed by spectroscopic and computational conformational analysis. Effects of photochemical structure modulation on molecular recognition in protein-ligand and supramolecular host-guest systems are discussed.

Phototriggerable peptidomimetic inhibitors of the enzyme M. tuberculosis ribonucleotide reductase (RNR) were obtained by incorporation of a stilbene based amino acid moiety into oligopeptides between 3-9 residues long (Paper I). Interstrand hydrogen bond probability in the E and Z forms of the peptidomimetics was used as a tool for predicting conformational preferences. Considerable differences in inhibitory potency for the E and Z photoisomers were demonstrated in a binding assay.

In order to advance the concept of photomodulable inhibitors, synthetic routes towards amino acid derivatives based on the more rigid stiff-stilbene chromophore were developed (Paper II).  The effect of E-Z isomerization on the conformational properties of peptidomimetic inhibitors incorporating the stiff-stilbene chromophore was also assessed computationally (Paper III). It was indicated that inhibitors with the more rigid amino acid derivative should display larger conformational divergence between photoisomers than corresponding stilbene derivatives.

Bisporphyrin tweezers with enediyne and stiff-stilbene spacers have been synthesized, and the conformational characteristics imposed by the spacers have been studied and compared to a glycoluril linked tweezer. The effects of spacers on tweezer binding of diamine guests and helicity induction by chiral guests have been investigated (Paper IV). Connections between spacer flexibility and host-guest binding strength have been established. The structural properties of the stiff-stilbene spaced tweezer made it particularly susceptible to helicity induction by both monotopic and bitopic chiral guests. Finally, the possibility of photochemical bite-size variation of tweezers with photoswitchable spacers has been assessed. Initial studies have shown that photoisomerization of the tweezers is possible without photochemical decomposition. Conformational analyses indicate that isomerization should impact binding characteristics of the tweezers to a significant extent (Paper V).

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. p. 61
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1329
Keywords
Bisporphyrin tweezers, peptidomimetics, host-guest systems, conformational analysis, supramolecular chemistry, photochemistry
National Category
Chemical Sciences
Research subject
Organic Chemistry; Chemistry with specialization in Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-267845 (URN)978-91-554-9431-5 (ISBN)
Public defence
2016-01-28, B41, BMC, Husargatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2016-01-04 Created: 2015-11-27 Last updated: 2016-01-13Bibliographically approved
Karlsson, C., Blom, M., Johansson, M., Jansson, A. M., Scifo, E., Karlén, A., . . . Gogoll, A. (2015). Phototriggerable peptidomimetics for the inhibition of Mycobacterium turberculosis ribonucleotide reductase by targeting protein-protein binding. Organic and biomolecular chemistry, 13(9), 2612-2621
Open this publication in new window or tab >>Phototriggerable peptidomimetics for the inhibition of Mycobacterium turberculosis ribonucleotide reductase by targeting protein-protein binding
Show others...
2015 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 13, no 9, p. 2612-2621Article in journal (Refereed) Published
Abstract [en]

Incorporation of an artificial amino acid 2 with a stilbene chromophore into peptidomimetics with three to nine amino acids yields phototriggerable candidates for inhibition of the binding between the R1 and R2 subunits of the M. tuberculosis ribonucleotide reductase (RNR). Interstrand hydrogen bond probability was used as a guideline for predicting conformational preferences of the photoisomers. Binding of these inhibitors has been rationalized by docking studies with the R1 unit. Significant differences in binding of the photoisomers were observed. For the shorter peptidomimetics, stronger binding of the Z isomer might indicate hydrophobic interactions between the stilbene chromophore and the binding site.

National Category
Organic Chemistry Medicinal Chemistry
Research subject
Chemistry with specialization in Organic Chemistry; Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-239491 (URN)10.1039/C4OB01926A (DOI)000350144600018 ()25580895 (PubMedID)
Funder
Swedish Research Council
Available from: 2014-12-28 Created: 2014-12-28 Last updated: 2018-01-11Bibliographically approved
Olsson, S. K., Benito Perez, O., Blom, M. & Gogoll, A.Effect of Ring Size on Photoisomerization Properties of Stiff Stilbene macrocycles.
Open this publication in new window or tab >>Effect of Ring Size on Photoisomerization Properties of Stiff Stilbene macrocycles
(English)Manuscript (preprint) (Other academic)
Abstract [en]

A series of stiff stilbene macrocycles have been studied in order to investigate the possible impact of macrocycle ring size on their photo-dynamic properties. The results show that reducing the ring size counteracts the photoisomerization ability of the macrocycles. However, even the smallest macrocycle studied (stiff stilbene subunits linked by a six carbon chain) showed some degree of isomerization when irradiated. DFT calculations of the energy differences between the E- and Z-isomers show the same trend as the experimental results. Interestingly the DFT study highlights that the energy difference between the E- and Z-isomers of even the largest macrocycle (linked by a twelve carbon chain) is significantly higher than that of the stiff stilbene unit itself. This indicates that a flexible chain may significantly affect the efficiency of photoisomerizations.

Keywords
Stiff stilbene cyclic photoisomerization
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-382215 (URN)
Funder
Swedish Research Council, 621-2012-3379Carl Tryggers foundation , CTS 16:156Swedish National Infrastructure for Computing (SNIC)
Available from: 2019-04-23 Created: 2019-04-23 Last updated: 2019-04-23
Blom, M., Olsson, S., Norrehed, S., Andersson, C.-H., Grennberg, H. & Gogoll, A.Photomodulable bis-porphyrin molecular tweezers as dynamic host systems for diamine guests.
Open this publication in new window or tab >>Photomodulable bis-porphyrin molecular tweezers as dynamic host systems for diamine guests
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Bisporphyrin molecular tweezers with an enediyne (1) or a stiff stilbene (2) photoswitchable spacer are proposed as systems for modulation of bitopic binding to diamine guests via E/Z photoisomerization. The photoisomerization has been monitored by UV-Vis and 1H NMR spectroscopy and occurs without side reactions such as Bergman cyclization. Possible applications are rationalized in terms of competitive binding involving monoamine/diamine mixtures, and are supported by conformational analysis of the envisioned host-guest complexes. Binding dynamics for conformationally flexible guests show significantly different performance of aliphatic 1,w-diamine guests with varying N-N distance.

Keywords
Bisporphyrin tweezers, supramolecular chemistry, photochemistry
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-267833 (URN)
Funder
Swedish Research Council, 621-2012-3379
Available from: 2015-11-27 Created: 2015-11-27 Last updated: 2016-01-13
Blom, M., Huang, H. & Gogoll, A.Photoswitchable peptidomimetics with a stiff-stilbene chromophore for inhibition of Mycobacterium tuberculosis RNR.
Open this publication in new window or tab >>Photoswitchable peptidomimetics with a stiff-stilbene chromophore for inhibition of Mycobacterium tuberculosis RNR
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Peptidomimetics incorporating two amino acids 1 and 2 with a stiff stilbene chromophore have been screened by a computational study and compared to a previously investigated analog 3 with stilbene chromophore. The effect of E-Z isomerization of the chromophores on the conformational properties of the petidomimetics was assessed via the frequency of hydrogen bonding between the two peptide strands attached to either side of the chromophore. Substantial differences between the three amino acids were thus indicated, in line with the anticipated effect of chromophore rigidity variation.

Keywords
Peptidomimetics, conformational analysis
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-267830 (URN)
Funder
Swedish Research Council, 621-2012-3379
Available from: 2015-11-27 Created: 2015-11-27 Last updated: 2016-01-13
Blom, M., Huang, H. & Gogoll, A.Synthesis and characterization of photoswitchable stiff-stilbene based amino acid derivatives.
Open this publication in new window or tab >>Synthesis and characterization of photoswitchable stiff-stilbene based amino acid derivatives
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Synthetic routes towards the Boc-protected amino acids 1 and 2 incorporating the stiff stilbene chromophore via the corresponding indanone carboxylic acids have been devised. Crucial steps are a reductive McMurry coupling of the indanone carboxylic acids, yielding stiff stilbene dicarboxylic acid esters. Hydrolysis to the monoester and conversion to the azides, followed by a Curtius rearrangement afforded the Boc-protected amino acid ester 1.

Keywords
Peptidomimetics
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-267829 (URN)
Funder
Swedish Research Council, 621-2012-3379
Available from: 2015-11-27 Created: 2015-11-27 Last updated: 2016-01-13
Organisations

Search in DiVA

Show all publications