Synthesis, structure and stability of a chiral imine-based Schiff-based ligand derived from L-glutamic acid and its [Cu4] complex

Article abstract of DOI:10.1016/j.molstruc.2016.07.100

Studies of the stability of a ligand derived from L-glutamic acid and ortho-vanillin and its new [Cu₄] complex are presented. The [Cu₄] complex contains a heterocubane [Cu^II₄O₄] core and pendant carboxylic groups increasing its solubility in water, also under basic conditions. The stability of the complex in different solvents is confirmed with ESI-MS studies and such experiments as successful recrystallization. The complex is stable also under physiological conditions whereas the ligand is partly decomposed to L-glutamic acid and ortho-vanillin.

Full text of DOI:10.1016/j.molstruc.2016.07.100

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Synthesis, structure and stability of a chiral imine-based Schiff-based ligand derived
from L-glutamic acid and its [Cu ] complex
4
Simon Muche, Irina Levacheva, Olga Samsonova, Anna Biernasiuk, Anna Malm,
Richard Lonsdale, Łukasz Popiołek, Udo Bakowsky, Małgorzata Hołyńska
PII:
S0022-2860(16)30784-0
10.1016/j.molstruc.2016.07.100
MOLSTR 22803
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 19 June 2016
Revised Date: 23 July 2016
Accepted Date: 25 July 2016
Please cite this article as: S. Muche, I. Levacheva, O. Samsonova, A. Biernasiuk, A. Malm, R. Lonsdale,
E. Popiołek, U. Bakowsky, M. Hołyńska, Synthesis, structure and stability of a chiral imine-based Schiff-
based ligand derived from L-glutamic acid and its [Cu ] complex, Journal of Molecular Structure (2016),
4
doi: 10.1016/j.molstruc.2016.07.100.
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ACCEPTED MANUSCRIPT
Synthesis, structure and stability of a chiral imine-
based Schiff-based ligand derived from L-glutamic
acid and its [Cu4] complex
Simon Muche,a Irina Levacheva,b Olga Samsonova,b Anna Biernasiuk,c Anna Malm,c Richard
Lonsdale,a,d Łukasz Popiołek,e Udo Bakowsky,b and Małgorzata Hołyńska*a
a Fachbereich Chemie and Wissenschaftliches Zentrum für Materialwissenschaften, Philipps-
Universität Marburg, Hans-Meerwein-Strasse, D-35043 Marburg, Germany. E-Mail:
holynska@staff.uni-marburg.de
b Institut für Pharmazeutische Technologie & Biopharmazie, Philipps-Universität Marburg,
Ketzerbach 63, D-35032 Marburg, Germany.
c Department of Pharmaceutical Microbiology, Medical University, Chodźki 1, 20-093 Lublin,
Poland.
d Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470, Mülheim an der
Ruhr, Germany.
e Department of Organic Chemistry, Medical University of Lublin, Chodźki 4A, 20-093 Lublin,
Poland.
KEYWORDS copper (II) • Schiff-base • stability •crystal structure
1

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ABSTRACT: Studies of the stability of a ligand derived from L-glutamic acid and ortho-vanillin
and its new [Cu4] complex are presented. The [Cu4] complex contains a heterocubane [CuII O4]
4
core and pendant carboxylic groups increasing its solubility in water, also under basic conditions.
The stability of the complex in different solvents is confirmed with ESI-MS studies and such
experiments as successful recrystallization. The complex is stable also under physiological
conditions whereas the ligand is partly decomposed to L-glutamic acid and ortho-vanillin.
Graphical Abstract
Synopsis: Structure and stability of a chiral Schiff-base ligand and its new [Cu4] complex are
presented.
Highlights
•
•
•
Stability of a chiral Schiff-base ligand and its new [Cu4] complex are reported
The complex shows high solubility in polar solvents due to pendant carboxylic groups
Initial studies of biological properties point out antifungal activity
2

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Introduction
Oligonuclear metal complexes with Schiff-base ligands have been shown to often display
antibacterial, antifungal, anti-inflammatory and antiviral activities.1 In spite of these
observations, attempts to rationalize them are scarcely available. For instance, Raman et al. 2a
studied Schiff bases derived from 1H-indole-2,3-dione (isatin) and 4-(2-aminoethyl)phenol
(tyramine) and their Cu, Ni, Zn complexes interacting with the minor groove of CT-DNA. The
increased antibacterial activity of the metal complexes was rationalized in terms of Tweedy’s
chelation theory on metal-ligand bonding enhancing the system’s liphophilicity and, as a
consequence, the ability to penetrate lipid membranes and to block the metal-binding sites of
microbial enzymes. Moreover, the highest activity of the Cu(II) complex was explained in terms
of the atomic radius / electronegativity of the Cu2+ ion leading to the conclusion that the
antimicrobial properties are more promising for ions with higher electronegativities and large
atomic radii. These considerations were completed with docking studies. Such theoretical reports
rationalizing the interaction with DNA and proteasome inhibition of some Schiff-base complexes
are available also for other systems. 2b-f
In particular, fungal infections (candidiasis) are a serious problem to civilization, increasing the
mortality of infants and individuals suffering from decreased immunity. The administration of
therapeutic doses of the currently available antimicrobial agents to patients leads to multiple side
effects.3 The most common adverse effects are allergic reactions, shifts in microflora balance and
the generation of resistance in pathogenic species. After misbalancing of the natural defense
system in the body, so follows the increase in the host vulnerability towards external pathogens,
leading to a more aggressive disease progression.4,5 To find the “golden ratio” in the interplay of
3