The nature and characteristics of the CH/π interaction are discussed by comparison with other weak molecular forces such as the CH/O and OH/π interaction. The CH/π interaction is a kind of hydrogen bond operating between a soft acid CH and a soft base π-system (double and triple bonds, C6 and C5 aromatic rings, heteroaromatics, convex surfaces of fullerenes and nanotubes). The consequences of CH/π hydrogen bonds in supramolecular chemistry are reviewed on grounds of recent crystallographic findings and database analyses. The topics include intramolecular interactions, crystal packing (organic and organometallic compounds), host/guest complexes (cavity-type inclusion compounds of cyclodextrins and synthetic macrocyclic hosts such as calixarenes, catenanes, rotaxanes and pseudorotaxanes), lattice-inclusion type clathrates (including liquid crystals, porphyrin derivatives, cyclopentadienyl compounds and C60 fullerenes), enantioselective clathrate formation, catalytic enantioface discriminating reactions and solid-state photoreaction. The implications of the CH/π concept for crystal engineering and drug design are evident.

CH/π hydrogen bonds in crystals

The copper(II) complex [Cu(tdp)(ClO4)].0.5H2O (1), where H(tdp) is the tetradentate ligand 2-[(2-(2-hydroxyethylamino)ethylimino)methyl]phenol, and the mixed ligand complexes [Cu(tdp)(diimine)]+ (2-5), where diimine is 2,2'-bipyridine (bpy) (2), 1,10-phenanthroline (phen) (3), 3,4,7,8-tetramethyl-1,10-phenanthroline (tmp) (4), and dipyrido-[3,2-d:2',3'-f]-quinoxaline (dpq) (5), have been isolated and characterized by analytical and spectral methods. Complexes 1 and [Cu(tdp)(phen)]ClO4 (3) have been structurally characterized, and their coordination geometries around copper(II) are described as distorted octahedral. The equatorially coordinated ethanolic oxygen in 1 is displaced to an axial position upon incorporating the strongly chelating phen, as in 3. The solution structures of all the complexes have been assessed to be square-based using electronic absorption and electron paramagnetic resonance (EPR) spectroscopy. The interaction of the complexes with calf thymus DNA (CT DNA) has been explored by using absorption, emission, and circular dichroic spectral and viscometric studies, and modes of DNA binding for the complexes have been proposed. Absorption spectral (Kb = 0.071 +/- 0.005 (2), 0.90 +/- 0.03 (3), 7.0 +/- 0.2 (4), 9.0 +/- 0.1 x 10(5) M(-1) (5)), emission spectral (Kapp = 4.6 (1), 7.8 (2), 10.0 (3), 12.5 (4), 25.0 x 10(5) M(-1) (5)), and viscosity measurements reveal that 5 interacts with DNA more strongly than the other complexes through partial intercalation of the extended planar ring of the coordinated dpq with the DNA base stack. Interestingly, only complex 4 causes a B to A conformational change upon binding DNA. All the complexes hydrolytically cleave pBR322 supercoiled DNA in 10% DMF/5 mM Tris-HCl/50 mM NaCl buffer at pH 7.1 in the absence of an activating agent, and the cleavage efficiency varies in the order 5 > 3 > 2 > 4 > 1 with 5 displaying the highest Kcat value (5.47 +/- 0.10 h(-1)). The same order of cleavage is observed for the oxidative cleavage of DNA in the presence of ascorbic acid as a reducing agent. Interestingly, of all the complexes, only 5 displays efficient photonuclease activity through double-strand DNA breaks upon irradiation with 365 nm light through a mechanistic pathway involving hydroxyl radicals. The protein binding ability of 1-5 has been also monitored by using the plasma protein bovine serum albumin (BSA), and 4 exhibits a protein binding higher than that of the other complexes. Further, the anticancer activity of the complexes on human cervical epidermoid carcinoma cell line (ME180) has been examined. Interestingly, the observed IC50 values reveal that complex 4, which effects conformational change on DNA and binds to BSA more strongly, exhibits a cytotoxicity higher than the other complexes. It also exhibits approximately 100 and 6 times more potency than cisplatin and mitomycin C for 24 and 48 h incubation times, respectively, suggesting that 4 can be explored further as a potential anticancer drug. Complexes 4 and 5 mediate the arrest of S and G2/M phases in the cell cycle progression at 24 h harvesting time, which progress into apoptosis.

Mixed-Ligand Copper(II)-phenolate Complexes: Effect of Coligand on Enhanced DNA and Protein Binding, DNA Cleavage, and Anticancer Activity

Oxidative DNA cleavage mediated by a new copper (II) terpyridine complex: crystal structure and DNA binding studies.

Two mononuclear fluorophore-labeled copper(II) complexes [Cu(nip)(acac)]+(2) and [Cu(nip)2]2+ (3), where fluorophore is 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (nip) (1) and acac is acetylacetone, have been synthesized and characterized by various techniques. The ligand 1 and complex 2 are structurally characterized by single-crystal X-ray diffraction. The coordination geometries around the copper are square planar in solid as well as solution state as evidenced by electron paramagnetic resonance (EPR) spectroscopy. The density functional calculations carried out on 1−3 have shown that electron-rich regions in the highest occupied orbital are localized on the naphthalene and partly on the phenanthroline moiety. Both complexes 2 and 3 in dimethyl sulfoxide (DMSO) exhibit near square planar structure around the metal ion in their ground state. Time-dependent density functional theory (TD-DFT) calculations reveal that Cu(II) ion in complex 2 shows tetrahedral coordination around the metal w...

Synthesis, Electronic Structure, DNA and Protein Binding, DNA Cleavage, and Anticancer Activity of Fluorophore-Labeled Copper(II) Complexes

Copper(II) complexes of tridentate pyridylmethylethylenediamines: Role of ligand steric hindrance on DNA binding and cleavage

Synthesis, structure and nuclease properties of several ternary copper(II) peptide complexes with 1,10-phenanthroline.

Reactivity of copper(II) peptide complexes with bioligands (benzimidazole and creatinine)

X-ray diffraction structure of a ternary copper(II) peptide complex (benzimidazole) (glycylglycinato) copper(II) trihydrate

The ternary complexes (glycylglycinato)(isocytosine)copper(II) dihydrate 1 and (glycylglycinato)(6-methylisocytosine)copper(II) monohydrate 2 have been prepared and characterised by X-ray diffraction, electrochemistry and optical, ESR and IR spectroscopy. The two compounds are slightly distorted square planar, with the four co-ordination sites occupied by the tridentate glycylglycine dianion [O(7), N(13) and N(10)] and N(3) of the pyrimidine base. An additional weak axial interaction exists between an oxygen of a water molecule O(W1) and the copper atom [Cu· · ·O(W1) distances 2.74 and 2.70 A respectively]. Spectroscopic and electrochemical data are in accord with the crystal structures. Although both compounds exhibit irreversible oxidation processes, the oxidation of CuII to CuIII is best performed with the isocytosine complex.

Bartomeu Adrover

Papers

Synthesis, structure and nuclease properties of several ternary copper(II) peptide complexes with 1,10-phenanthroline.

Reactivity of copper(II) peptide complexes with bioligands (benzimidazole and creatinine)

X-ray diffraction structure of a ternary copper(II) peptide complex (benzimidazole) (glycylglycinato) copper(II) trihydrate

Synthesis and structure of isocytosine ternary copper(II) complexes

Synthesis and structure of peptide–copper(II)–isocytosine ternary complexes