Playing with Structural Parameters: Synthesis and Characterization of Two New Maltol-Based Ligands with Binding and Antineoplastic Properties

Abstract

Two maltol-based ligands, N,N′-bis((3-hydroxy-4-pyron-2-yl)methyl)-1,4-piperazine (L1) and N,N′,N′-tris((3-hydroxy-4-pyron-2-yl)methyl)-N-methylethylendiamine (L2), were synthesized and characterized. L1 and L2, containing, respectively, two and three maltol units spaced by a diamine fragment, were designed to evaluate how biological and binding features are affected by structural modifications of the parent compound malten. The acid-base behavior and the binding properties towards transition, alkaline-earth (AE) and rare-earth (RE) cations in aqueous solution, studied by potentiometric, UV-Vis and NMR analysis, are reported along with biological studies on DNA and leukemia cells. Both ligands form stable complexes with Cu(II), Zn(II) and Co(II) that were studied as metallo-receptors for AE and RE at neutral pH. L1 complexes are more affected than L2 ones by hard cations, the L1-Cu(II) system being deeply affected by RE. The structural modifications altered the mechanism of action: L1 partially maintains the ability to induce structural alterations of DNA, while L2 provokes single strand (nicks) and to a lesser extent double strand breaks of DNA.

A Tetranuclear Copper(II)/Calcium(II) Complex as Dual Chemosensor for Colorimetric and Fluorescent Detection of Non‐Steroidal Anti‐Inflammatory Drugs

“…[50,51] The latter belongs to a class of molecules containing two maltol (3-hydroxy-2-methyl-4-pyrone) units linked to a polyamine fragment and also exerts antineoplastic activity. [52][53][54][55] In the solid state complexes, the four Cu 2 + /Ca 2 + /Ca 2 + /Cu 2 + metal ions arrange in a chain, bridged by oxygen atoms belonging to the Malten ligands. Briefly, the complexes form in aqueous solution by mixing L and Cu 2 + in an equimolar ratio around pH 7 in the presence of a large excess of Ca 2 + .…”

“…Recently we reported hetero‐tetranuclear complexes incorporating both a transition metal ion (Cu 2+ ) and a main group cation (Ca 2+ ) assembled by the ligand Malten ( L , N,N’‐bis((3‐hydroxy‐4‐pyron‐2‐yl)methyl)‐N,N’‐dimethylethylendiamine, Figure 1). [50,51] The latter belongs to a class of molecules containing two maltol (3‐hydroxy‐2‐methyl‐4‐pyrone) units linked to a polyamine fragment and also exerts antineoplastic activity [52–55] . In the solid state complexes, the four Cu 2+ /Ca 2+ /Ca 2+ /Cu 2+ metal ions arrange in a chain, bridged by oxygen atoms belonging to the Malten ligands.…”

Crystal Structure, Hirshfeld Surface Analysis and Energy Framework Calculations of Different Metal Complexes of a Biphenol-based Ligand: Role of Solvent and Transition Metal Ion

“…When looking at transition metal complexes, the metal center plays a key role in defining the molecular conformation, due to specific requirements that span different geometries, from square planar to square pyramid to octahedral, as examples for coordination number 4, 5 and 6 [15]. The metal ion could also provide the preorganization of the structure, aspect that sometimes is relevant to further applications of the complex, such as the binding in aqueous solution of species generally 2 difficult to pick up in such environment or the selective binding of guests usually difficult to distinguish in solution [16][17][18]. Different metal complexes of the same ligand can be obtained when using diverse crystallization solvents.…”

Glucosamine and maltol anchored Zinc(II) complex of COVID-19 health supplement relevance: DFT collaborated spectroscopic formulation with profound biological implications

“…Maltol is also a natural organic compound commonly used as a flavor enhancer [ 19 ]. This compound is either extracted from plants like larch trees, pine needles, malt, and oils or maybe obtained synthetically [ 20 ]. This is a well-known “artificial sweetener” and good flavoring agent to produce a ‘fresh-baked’ taste and smell in bread, chocolate, soft drinks, ice cream, jam, etc.…”