This Special Issue of the International Journal of Molecular Science comprises a comprehensive
study on "Metal Complex Interactions with Nucleic Acids and/or DNA". This Special
Issue has been inspired by the important contribution of Prof. Nick Hadjiliadis in
the field of palladium or/and platinum/nucleic acid interactions. It covers a selection
of recent research and review articles in the field of metal complex interactions
with nucleic acids and/or DNA.
Metal complexes have long been recognized as critically important components of nucleic
acid chemistry, both in the regulation of gene expression and as promising therapeutic
agents. The ability to recognize and understand how metal complexes interact with
DNA at the molecular level has become an active research area at the interface between
biological inorganic chemistry, molecular biology, and medicine. Arguably the most
prominent drug which contains a metal is cisplatin, the most widely used anti-cancer
drug. The success of cisplatin in chemotherapy and the clarification of its mechanism
of action through its interaction with DNA has motivated a large number of studies
on metal complex interactions with nucleic acids or/and DNA. Thus, the reader of this
Special Issue will gain an appreciation of the real role of the interactions of metal
complexes with nucleic acids or/and DNA in modern medicine.
This Special Issue on "Metal complex Interactions with Nucleic Acids and/or DNA" provides
an overview of this increasingly diverse field, presenting recent developments and
the latest research with particular emphasis on metal-based drugs and metal ion toxicity.
Inorganic biochemistry or bioinorganic chemistry is a multidiscipline field which
involves inorganic chemistry, biochemistry, spectroscopy, material science, biology,
and medicine. The introduction of metal ions or metal ion binding components into
a biological system for the treatment of diseases is one of the main subdivisions
in the field of inorganic biochemistry. Nowadays, at the forefront of the field is
the development of new metallodrugs for diagnostics (radiopharmaceuticals drugs),
medicines (anticancer, antimicrobial/antiparasitic, therapeutic radiopharmaceuticals,
photochemotherapeutic metallodrugs, antiarthritic, antidiabetes, antiviral, metallodrugs
addressing deficiencies syndromes), and tools for chemical biology, biocatalysis,
and bioelectronics, as well as the characterization of metalloproteins, enzymes, and
their model complexes. Recently, biomaterials have been applied in many cases such
as cardiovascular medical devices, orthopedic and dental applications, ophthalmologic
applications, bioelectrodes and biosensors, burn dressings and skin substitutes, sutures,
and drug delivery systems. For the coming years, the well-defined bioavailability,
absorption, distribution, metabolism, and excretion of metal-based drugs will be the
main target of new metallodrugs. The use of nanoparticles, micelle emulsions, and
liposomal formulations can open new opportunities for improved delivery, cell uptake,
and targeting.
Emeritus Professor Nick Hadjiliadis is one of the pioneers in the field of bioinorganic
chemistry. He graduated from the University of Athens, and subsequently earned a Masters
in Science from the University of Montreal and a Doctor of Chemistry, PhD from the
University of Montreal in 1975. He served as a Professor of Inorganic and General
Chemistry at the Department of Chemistry of the University of Ioannina, Greece, since
1980. He worked on the interaction of metal ions with nucleobases and nucleosides,
as well as with DNA and RNA. This pioneering work led to the first conclusions elucidating
the mechanism of the antitumoral action of cisplatin. His research interests also
included: (i) the synthesis, characterization, and study of the antitumor properties
of new metal complexes (e.g., Pt, Pd, Sn, Sb, etc.); (ii) the study of metalloenzyme
models and the clarification of their mechanism of action. His research on thiamine
enzymes in the presence of divalent metal ions, for which he proposed a mechanism,
was also a pioneering work in the field of enzyme/metal ion interactions. He also
studied (iii) the mechanism of action of superoxide dismutase, Cu(II), and Zn(II);
(iv) peptide interactions with metal ions, as models of enzymes or other biological
systems; (v) the involvement of metal ions such as Ni(II) and Cu(II) in carcinogenesis;
(vi) the biocatalysis of new materials; (vii) the mechanism of action of anti-thyroid
drugs; (viii) organometallic chemistry, etc. He has numerous publications (up to 260),
which have been cited more than 7000 times with an h-index of 44. He has been invited
to 70 international conferences (as a Lead Speaker). He has coordinated many research
and teaching programs. Important international conferences dedicated to the field
of inorganic biochemistry—such as 5-ISABC, HALCHEM-III, 12-EURASIA, etc.—have been
organized and chaired by him. Furthermore, he mentored many scientists, initiating
their careers as academicians worldwide. Special attention should be paid to his contribution
to the foundation and operation of the Interdisciplinary Program of Postgraduate Studies
in Bioinorganic Chemistry, which he led for a decade. His contribution to the field
of Inorganic-Bioinorganic Chemistry is undoubtedly superior in quality and unique
for a Greek scientist. Overall, he contributed to the progress of inorganic chemistry
not only at the University of Ioannina, Greece, but in the whole nation.
Recognizing this contribution of Emeritus Professor Nick Hadjiliadis to the field
of inorganic biochemistry and especially to the field of palladium or/and platinum/nucleic
acid interactions, it is our honour to dedicate the prologue of this commemorative
issue of the International Journal of Molecular Sciences to him.
This Special Issue is composed of 14 articles, which are briefly reviewed below.
Yu-Wen Chen et al. showed that the i-motif DNA sequence may transition to a base-extruded
duplex structure with a GGCC tetranucleotide tract when it is bound to the (CoII)-mediated
dimer of chromomycin A3 [1]. G. Momekov et al. investigated two paramagnetic palladium(III)
complexes of hematoporphyrin IX for their ability to process DNA adducts as well as
for their antineoplastic and apoptogenic activities [2]. E. Makkonen et al. reported
a combined quantum mechanics/molecular mechanics molecular dynamics and time-dependent
density functional study of silver-mediated deoxyribonucleic acid nanostructures [3].
S. Liu et al. investigated the interactions between ruthenium(II) complexes and 15-mer
single- and double-stranded oligodeoxynucleotides and they tested the thermodynamic
base and sequence selectivity [4]. G.K. Latsis et al. investigated two polyorganotic
acetate complexes against DNA with possible implementation towards breast cancer cells
[5]. S. Savino et al. tested the ability of platinum prodrugs of kiteplatin with a-lipoic
acid in the axial position to target in mitochondria [6]. Q.Y. Yang et al. tested
the molecular mechanism of two transition metal complexes with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol
against tumor cells [7]. M. Hande et al. described the synthesis and hybridization
properties of short oligonucleotides incorporating cyclopalladated benzylamine “warheads”
at their 5′-termini [8]. M.F. AlAjmi et al. evaluated the benzimidazole-derived biocompatible
copper(II) and zinc(II) complexes as anticancer chemotherapeutics [9]. T. Qin et al.
examined the binding of zinc cationic porphyrin towards B-DNA and Z-DNA [10] A.B.
Olejniczak et al. presented an overview of the methods for incorporating metal centers
into nucleic acids based on metal–boron cluster complexes (metallacarboranes) as the
metal carriers [11]. Y.H. Lai et al. reviewed the mechanisms by which the regulation
of copper homeostasis modulates the chemosensitivity of tumors to platinum drugs [12].
V. Murray et al. reviewed the abilities of bleomycin to interact with DNA [13]. N.C.
Sabharwal et al. investigated the interactions between spermine-derivitized tentacle
2 porphyrins and the human telomeric DNA G quadruplex [14].