Design and synthesis of model compounds: study of stereoelectronic, steric effects, reactive intermediates, catalytic enantioselective hydrogenation and dynamic protection of functional groups
1-Aza-2-adamantanone – a model compound. The fragment which mimics the cis–trans amide isomerization transition state is shown in redPhotocontrollable
antibiotic, an analogue of the natural antibiotic
gramicidin S
The areas of scientific interests of Igor V. Komarov are
medicinal chemistry and
synthesis of model compounds, which can be used to obtain new knowledge in
biochemistry,
stereochemistry,
theoretical chemistry,
catalysis. Igor has over 125
peer reviewedresearch papers,
h-index 31,[8] has guided 8
PhD students to date. Igor's scientific group puts the main focus on developing of novel synthetic methods and design of theoretically interesting molecules, part of which were created and synthesized in tight collaboration with Prof. Anthony J.
Kirby from
the University of Cambridge (United Kingdom). One of such collaborative projects was synthesis, study of stereochemistry and
chemical properties of 1-aza-2-adamantanone and its derivatives. A trimethyl-substituted derivative ("the most twisted amide",[9] "Kirby's amide"[10]) was designed in the Prof. Kirby's laboratory and synthesized by Igor in 1997 during his postdoctoral stay in Cambridge. In 2014, a
parent molecule was made in Igor's group in collaboration with Prof. Kirby. The compound modelled the transition state of cis-trans isomerization of
amides and allowed obtaining fundamental
knowledge about the
amide bond.[11]
Although Igor's interest to the synthesis of chiral ligands has not been faded, he changed the general direction of his research once more, and now he works in the area of
drug design.[7] One of the main design principle is restriction of
conformational mobility of the
drug candidatemolecules.[19][20] Prof. Komarov's research group developed many approaches to synthesis of conformationally restricted
amines and
amino acids - the
building blocks for drug design.[19][21] Numerous conformationally restricted
fluorine-containing amino acids were also designed and synthesized, with a purpose of using them as labels to study
peptides in
lipid bilayers by
solid-state NMR spectroscopy.[22]
Igor V. Komarov's group made a contribution to design and synthesis of light-controllable biologically active compounds -
photocontrollable peptides - potential candidates for
photopharmacology drugs. Photopharmacology drugs can be
administered in the inactive,
non-toxic form, and then activated ("switched on") by
light only when and where required to treat localized
lesions (e.g.in
solid tumors).[23] The activation by light can be done with very high spatiotemporal precision in the lesion site, leaving the rest of the
patient body unaffected.[24][25] After the treatment, the photopharmacology drugs can be inactivated ("switched off") by light in order to diminish
side-effects and
environmental burden.[23]
Another research direction in the Igor V. Komarov's scientific group is navigation of
chemical space. A method of structural comparison for organic molecules was developed which employed exit vector plot analysis.[26]Enumeration of molecules (exhaustive generation of all theoretically possible structures) was carried out for some classes of organic compounds, for example, for conformationally restricted
diamines.[27]
Igor V. Komarov has a Ukrainian patent,[29] 2 international patents,[30][31] is a co-authors of
text-books on NMR spectroscopy.[32]
Scientific projects
Igor V. Komarov was a coordinator of scientific projects financed by the Ministry of Education and Science of the Ukraine (three applied projects devoted to design of therapeutic peptides, including photocontrolled
[1]), Alexander von Humboldt Foundation (Institute Partnershaft and Research Linkage Programs, in collaboration with Karlsruhe University (Karlsruhe, Germany)
[2] and Leibniz Institute of Molecular Pharmacology (Berlin, Germany)
[3]), private companies Degussa (the project was devoted to development of large-scale production of a ligand for Rhodium-based catalysts of asymmetric hydrogenation) and Enamine (six medicinal chemistry projects, lead discovery and lead optimization). He is currently a coordinator of a European Horizon2020 Research and Innovation Staff Exchange (RISE) Programme (2016–2019) Grant Agreement number: 690973
[4], the title of the project – “Peptidomimetics with Photocontrolled Biological Activity”.
Awards and grants
NATO Research Award (
postdoctoral fellowship, 01.1996–01.1997, The University of Cambridge, United Kingdom);
INTAS grants (research visits, 08.1993 and 10.1994,The University of Cambridge, United Kingdom);
ISF grants (1998, research project, Taras Shevchenko National University of Kyiv);
^Komarov, Igor.
"Biography". Encyclopedia of Taras Shevchenko National University of Kyiv. Archived from
the original on 2017-08-10. Retrieved 2017-08-10.
^Liu, Chengwei; Szostak, Michal (2017-05-29). "Twisted Amides: From Obscurity to Broadly Useful Transition-Metal-Catalyzed Reactions by N−C Amide Bond Activation". Chemistry – A European Journal. 23 (30): 7157–7173.
doi:
10.1002/chem.201605012.
ISSN1521-3765.
PMID27813178.
^Komarov, Igor V.; Yanik, Stanislav; Ishchenko, Aleksandr Yu.; Davies, John E.; Goodman, Jonathan M.; Kirby, Anthony J. (2015-01-21). "The Most Reactive Amide As a Transition-State Mimic For cis–trans Interconversion". Journal of the American Chemical Society. Vol. 137, no. 2. pp. 926–930.
doi:
10.1021/ja511460a.
ISSN0002-7863.
^V. Komarov, Igor; Yu. Kornilov, Mikhail; V. Turov, Aleksandr; V. Gorichko, Marian; O. Popov, Vladimir; A. Tolmachev, Andrey; J. Kirby, Anthony (1995-11-06). "Phosphorylation of 1,3-Di(N-alkyl)Azoles by Phosphorus(V) Acid Chlorides — a Route to Potential Haptens Derived from Phosphinic Acids". Tetrahedron. 51 (45): 12417–12424.
doi:
10.1016/0040-4020(95)00797-C.
^Budnyak, Tetyana M.; Strizhak, Alexander V.; Gładysz-Płaska, Agnieszka; Sternik, Dariusz; Komarov, Igor V.; Kołodyńska, Dorota; Majdan, Marek; Tertykh, Valentin А. (2016-08-15). "Silica with immobilized phosphinic acid-derivative for uranium extraction". Journal of Hazardous Materials. 314: 326–340.
doi:
10.1016/j.jhazmat.2016.04.056.
PMID27177215.
^Komarov, Igor V.; Monsees, Axel; Kadyrov, Renat; Fischer, Christine; Schmidt, Ute; Börner, Armin (2002-08-14). "A new hydroxydiphosphine as a ligand for Rh(I)-catalyzed enantioselective hydrogenation". Tetrahedron: Asymmetry. 13 (15): 1615–1620.
doi:
10.1016/S0957-4166(02)00372-5.
^
abGrygorenko, Oleksandr O.; Radchenko, Dmytro S.; Volochnyuk, Dmitriy M.; Tolmachev, Andrey A.; Komarov, Igor V. (2011-09-14). "Bicyclic Conformationally Restricted Diamines". Chemical Reviews. Vol. 111, no. 9. pp. 5506–5568.
doi:
10.1021/cr100352k.
ISSN0009-2665.
^Grygorenko, Oleksandr O.; Artamonov, Oleksiy S.; Komarov, Igor V.; Mykhailiuk, Pavel K. (2011-02-04). "Trifluoromethyl-substituted cyclopropanes". Tetrahedron. 67 (5): 803–823.
doi:
10.1016/j.tet.2010.11.068.
^Chernykh, Anton V.; Radchenko, Dmytro S.; Grygorenko, Oleksandr O.; Daniliuc, Constantin G.; Volochnyuk, Dmitriy M.; Komarov, Igor V. (2015-04-17). "Synthesis and Structural Analysis of Angular Monoprotected Diamines Based on Spiro[3.3]heptane Scaffold". The Journal of Organic Chemistry. Vol. 80, no. 8. pp. 3974–3981.
doi:
10.1021/acs.joc.5b00323.
ISSN0022-3263.
^Kubyshkin, Volodymyr (2012). Trifluoromethyl-substituted α-amino acids as solid-state 19F NMR labels for structural studies of membrane-bound peptides. Fluorine in Pharmaceutical and Medicinal Chemistry: From Biophysical Aspects to Clinical Applications. pp. 91–138.