Crystal structure of [Cu(N-quinolin-8-yl-p-toluenesulfonamidate)(2)]: study of its interaction with DNA and hydrogen peroxide.

A new copper complex with N-quinolin-8-yl-p-toulenesulfonamide has been prepared and characterised. The compound crystallises in the triclinic system, space group P1, with a=13.457(3), b=15.067(5), c=18.589(3) A; alpha=112.05(2), beta=93.92(2), gamma=108.30(2) degrees and Z=4. The geometry of the Cu(II) ion is distorted square planar. The N-quinolin-8-yl-p-toulenesulfonamidate anion behaves as a bidentate ligand through the N(sulfonamidate)and N(quinoline) atoms. The complex does not cleave DNA in the presence of hydrogen peroxide.     

Radical-induced DNA damage by cytotoxic square-planar copper(II) complexes incorporating o-phthalate and 1,10-phenanthroline or 2,2'-dipyridyl

DNA-targeting copper(II) reagents have emerged as suitable drug candidates owing to the clinical success of the copper-activated, natural chemotherapeutic drug bleomycin. This agent and the synthetic chemical nuclease copper(II) bis-1,10-phenanthroline represent important templates for inorganic drug design owing to their ability to initiate free radical DNA scission. Herein, we report the synthesis and biological properties of 1:1:1 square-planar copper(II) complexes incorporating the dicarboxylate o-phthalate and 1,10-phenanthroline (1) or 2,2'-dipyridyl (2) ligands. Their broad-spectrum chemotherapeutic potential has been assessed at 24- and 96-h intervals, along with that of the clinical agent cisplatin, using breast (MCF-7), prostate (DU145), colon (HT29), and intrinsically cisplatin-resistant ovarian (SK-OV-3) human cancer cells. 1 represents a potent cytotoxic agent with IC(50) values ranging from 5.6 to 3.4μM across all cell lines, including SK-OV-3. The production of endogenous reactive oxygen species within SK-OV-3 cancer cells was monitored using the fluorophore 2',7'-dichlorodihydrofluorescin diacetate, and results indicate a concentration-dependent propensity toward ROS generation by 1 and 2 that mirrors their antitumoral behavior. DNA interaction studies, using fluorescence and viscosity measurements, were conducted in tandem with the DNA-targeting drugs actinomycin D and pentamidine, using calf thymus DNA, poly[d(A-T)(2)], and poly[d(G-C)(2)], with intercalation of 1 and 2 at the minor groove appearing to be the likely interaction mode. DNA cleavage reactions using superhelical plasmid DNA, in the presence of exogenous reductant, l-ascorbic acid, revealed excellent agreement between double-stranded DNA scission capability and antitumoral IC(50) concentration. The presence of double-strand DNA breaks (DSBs) was confirmed within SK-OV-3 cancer cells using immunodetection of γ-H2AX foci by confocal microscopy and flow cytometry, with complex 1 quantitatively producing superior numbers of DSBs compared with complex 2. Superoxide dismutase and catalase mimetic activity assays were conducted, and these activities are related to the ability of both complexes to cleave DNA through free radical generation.     

DNA binding of iron(II) mixed-ligand complexes containing 1,10-phenanthroline and 4,7-diphenyl-1,10-phenanthroline

Absorption spectroscopy and circular dichroism (CD) have been used to characterize the DNA binding of [Fe(phen)3]2+, [Fe(phen)2(DIP)]2+ and [Fe(phen)(DIP)2]2+ where phen and DIP stand for 1,10-phenanthroline and 4,7-diphenyl-1,10-phenanthroline, respectively. Both [Fe(phen)3]2+ and [Fe(phen)2(DIP)]2+ bind weakly to calf thymus DNA (CT-DNA) in an electrostatic mode, while [Fe(phen)(DIP)2]2+ binds more strongly to CT-DNA, possibly in an intercalation mode. The hypochromicity, red shift and Kb increase in the order [Fe(phen)3]2+ < [Fe(phen)2(DIP)]2+ < [Fe(phen)(DIP)2]2+ in accordance with the increase in size and hydrophobicity of the iron(II) complexes. The thermodynamic parameters obtained suggest that the DNA binding of both [Fe(phen)3]2+ and [Fe(phen)2(DIP)]2+ is entropically driven, while that of [Fe(phen)(DIP)2]2+ is enthalpically driven. A strong CD spectrum in the UV and visible region develops upon addition of CT-DNA into the racemate solution of each iron(II) complex (Pfeiffer effect). This has revealed that a shift in diastereomeric inversion equilibrium takes place in the solution to yield an excess of one of the DNA-complex diastereomers. The striking resemblance of the CD spectral profiles to those of the pure delta-enantiomer indicates that the delta-enantiomer of the iron(II) complexes is preferentially bound to CT-DNA. The mechanism of the development of Pfeiffer CD is proposed on the basis of kinetic studies on the DNA binding of the racemic iron(II) complexes.     

Crystal structure and nuclease activity of mono(1,10-phenanthroline) copper complex

The hydroxo-bridged dinuclear copper (II)/phen complex [Cu(2)(phen)(2)(OH)(2)(H(2)O)(2)][Cu(2)(phen)(2)(OH)(2)Cl(2)]Cl(2).6H(2)O (phen=1,10-phenanthroline) has been prepared and characterized by single crystal X-ray diffraction. The coordinated area of the complex shows two distorted [CuN(2)O(2)O(w)] and [CuN(2)O(2)Cl] square-pyramidal and one strictly planar configuration CuO(2)Cu involving two O atoms of hydroxo-bridged, Cu(2+) cations, N atoms of two phen ligands and disorder solvate water and chlorine anions. In the presence of H(2)O(2), the complex of mono(1,10-phenanthroline)copper exhibits higher activity as a nuclease than bis(1,10-phenanthroline)copper.     

Interactions of mixed ligand ruthenium(II) complexes containing an amino acid and 1,10-phenanthroline with DNA

Mixed ligand ruthenium(II) complexes containing an amino acid (AA) and 1,10-phenanthroline (phen), i.e. [Ru(AA)(phen)₂]ⁿ⁺ (n=1,2, AA=glycine (gly), l-alanine (l-ala), l-arginine (l-arg)) have been synthesized. The interactions of these complexes and [Ru(phen)₃]²⁺ with DNA have been examined by absorption, luminescence, and circular dichroism spectroscopic methods. Absorption spectral properties revealed that [Ru(AA)(phen)₂]⁺ (AA=gly, l-ala) interacted with CT-DNA by the electrostatic binding mode. [Ru(l-arg)(phen)₂]²⁺ exhibited the greatest hypochromicity, red shift, and binding constant, indicating that this complex may partially intercalate into the base-pairs of DNA. These results were also suggested by luminescence spectroscopy. CD spectral properties have been examined to understand the detailed interactions of the ruthenium(II) complexes with artificial DNA. In the case of Δ-[Ru(l-arg)(phen)₂]²⁺, the solution on adding [poly(dG-dC)]₂ exhibited two well-defined positive peaks, which the shorter and longer wavelength peaks were assigned as originating from the major and the minor groove binding modes, respectively. Then, the solution on adding [poly(dA-dT)]₂ exhibited only one positive peak, which was assigned as a peak corresponding to the minor groove binding mode.     

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

Three new ternary peptide-Cu(II)-1,10-phenanthroline (phen) complexes, [Cu(L-ala-gly)(phen)].3.5H(2)O 1, [Cu(L-val-gly)(phen)] 2 and [Cu(gly-L-trp)(phen)].2H(2)O 3, have been prepared and structurally characterised. These compounds exist as distorted square pyramidal complexes with the five co-ordination sites occupied by the tridentate peptide dianion and the two heterocyclic nitrogens of the phenanthroline ligand. The bulk of the lateral chain in the peptide moiety determines the relative disposition of the phen ligand. Thus, in [Cu(L-val-gly)(phen)] 2, the phenanthroline plane is deviated towards the opposite side of the isopropyl group of the L-valine moiety. On the other hand, in [Cu(gly-L-trp)(phen)].2H(2)O 3 the absence of stacking interactions between phen and indole rings and the presence of an intramolecular CH...pi interaction should be pointed out. These complexes exhibit significant differences in their nuclease activity which depends on the nature of the peptidic moiety, the complex [Cu(gly-L-trp) (phen)].2H(2)O 3 being the most active.     

Ternary copper(II) complexes with hippurate derivatives and 1,10-phenanthroline: Synthesis and biological activity

Several new Cu-hippurate derivative-phenanthroline ternary complexes have been prepared. The X-ray structure of one of them, [Cu(hip)(phen)₂]⁺·(hip⁻) (2) (where hip is hippurate and phen is 1,10-phenanthroline) has been solved. The structure of this new compound shows important differences (3D-pattern) to other similar related complexes (2D-pattern). A study of the biological activity of [Cu(hip)(phen)₂]⁺·(hip⁻)·2H₂O (2), [Cu(BGG)(phen)₂]⁺·(BGG⁻)·6H₂O (3), [Cu(B^IGG)₂(phen)](H₂O) (4) and [Cu(I-hip)(bpy)₂]⁺·(I-hip⁻)·3.5H₂O (5) (where I-hip is ortho-iodohippurate, BGG corresponds to benzoylglycilglycine, and B^IGG is ortho-iodobenzoylglycilglycine) is included and compared with the anti-proliferative activity of [Cu(I-hip)(phen)₂]⁺·(I-hip⁻)·7H₂O (1) previously described, resulting in a greater cytotoxic activity of the compounds with 1,10-phenanthroline instead of those with 2,2′-bipyridyl, in the same way that removing iodine substitution or lengthening the peptidic chain diminishes the activity of compounds compared with 1. The presence of an ortho-iodine group and the direct bond between Ar-CO and glycine moieties yield to the best results.     

DNA interaction of new copper(II) complexes with sulfonamides as ligands

New copper(II) complexes with sulfonamide ligands have been prepared and characterized. Sulfonamide ligands were prepared through a reaction between 8-aminoquinoline and either 2-mesitylene (Hqmesa), 4-tert-butylbenzene (Hqtbsa), or alpha-toluene (Halphaqtsa) sulfonyl chlorides. The structural analysis carried out for complex [Cu(alphaqtsa)(2)] indicated that the local environment of the Cu(II) cation is between a square planar and a tetrahedral geometry, with stacking of the benzene rings of the sulfonyl ligands between neighbor molecules. Powder EPR spectra at room temperature gave rhombic spectra for the [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] complexes and an axial spectrum for the [Cu(qtbsa)(2)] complex, probably due to the steric hindrance of the methyl groups. Complexes [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] are artificial chemical nucleases that degrade DNA in the presence of sodium ascorbate. A study of the radical scavengers revealed that the ROS (reactive oxygen species) involved in the DNA damage were hydroxyl, singlet oxygen-like species, and superoxide anion.     

Homoleptic copper(II) and copper(I) complexes of 5,6-dihydro-5,6-epoxy-1,10-phenanthroline. Six-coordinate copper(I) in solution

Reaction of 5,6-dihydro-5,6-epoxy-1,10-phenanthroline (L) with Cu(ClO₄)₂·6H₂O in methanol in 3:1 M ratio at room temperature yields light green [CuL₃](ClO₄)₂·H₂O (1). The X-ray crystal structure of the hemi acetonitrile solvate [CuL₃](ClO₄)₂·0.5CH₃CN has been determined which shows Jahn-Teller distortion in the CuN₆ core present in the cation [CuL₃]²⁺. Complex 1 gives an axial EPR spectrum in acetonitrile-toluene glass with g_|| = 2.262 (A_|| = 169 × 10⁻⁴ cm⁻¹) and g_⊥ = 2.069. The Cu(II/I) potential in 1 in CH₂Cl₂ at a glassy carbon electrode is 0.32 V versus NHE. This potential does not change with the addition of extra L in the medium implicating generation of a six-coordinate copper(I) species [CuL₃]⁺ in solution. B3LYP/LanL2DZ calculations show that the six Cu-N bond distances in [CuL₃]⁺ are 2.33, 2.25, 2.32, 2.25, 2.28 and 2.25 Å while the ideal Cu(I)-N bond length in a symmetric Cu(I)N₆ moiety is estimated as 2.25 Å. Reaction of L with Cu(CH₃CN)₄ClO₄ in dehydrated methanol at room temperature even in 4:1 M proportion yields [CuL₂]ClO₄ (2). Its ¹H NMR spectrum indicates that the metal in [CuL₂]⁺ is tetrahedral. The Cu(II/I) potential in 2 is found to be 0.68 V versus NHE in CH₂Cl₂ at a glassy carbon electrode. In presence of excess L, 2 yields the cyclic voltammogram of 1. From ¹H NMR titration, the free energy of binding of L to [CuL₂]⁺ to produce [CuL₃]⁺ in CD₂Cl₂ at 298 K is estimated as −11.7 (±0.2) kJ mol⁻¹.     

Crystal structure, magnetic and electrochemical properties of five-coordinate copper (II) complexes with 1,10-phenanthroline-5,6-dione

Three new five-coordinate Cu^II complexes, [Cu(tpy)(phen-dione)](PF₆)₂, [Cu(phen)(phen-dione)Cl]PF₆ and [Cu(bpy)(phen-dione)Cl]PF₆ (tpy = 2,2′;6′,2″-terpyridine, phen = 1,10-phenanthroline and phen-dione = 1,10-phenanthroline-5,6-dione) have been prepared and characterized by elemental analysis, IR and UV-Vis spectroscopies and cyclic voltammetry.The complex of [Cu(tpy)(phen-dione)](PF₆)₂ crystallized with one molecule of acetonitrile. The ortep drawing of [Cu(tpy)(phen-dione)](PF₆)₂ · CH₃CN shows that the coordination geometry around Cu^II is a distorted trigonal- bipyramid. Due to the steric hindrance of in the unit cell, the tpy ligands in each complex cation cannot interact in a π-π fashion. The effective magnetic moment (μ_eff) of the complexes was measured by the Evans method. The cyclic voltammograms at Pt disk electrode for these complexes display only one reversible Cu(II)/Cu(I) redox couple.     

Palladium(II) complexes of 1,10-phenanthroline: Synthesis and X-ray crystal structure determination

Two palladium(II) complexes, [Pd(phen)(NCCH₃)₂][O₃SCF₃]₂ (1) and [Pd(phen)(μ-OH)]₂[O₃SCF₃]₂ · 2H₂O (2) (where phen = 1,10-phenanthroline), have been crystallized following the reaction of Pd(phen)Cl₂ with silver triflate, Ag(O₃SCF₃), in acetonitrile and water, respectively. The structures of both complexes are based on a Pd(phen)²⁺ metal core, with two acetonitrile molecules binding in a monodentate fashion in complex 1 and two hydroxo bridges holding together two cores to form a dimer in complex 2. Additionally, both complexes present a hydrogen bonded 3-D network involving the triflate anions in 1, and water and triflate anions in 2. Both complexes have been characterized by infrared and ¹H NMR spectroscopy and their crystal structures determined by X-ray crystallography.     

Oxidative damage to DNA by 1,10-phenanthroline/<Emphasis Type="SmallCaps">l</Emphasis>-threonine copper (II) complexes with chlorogenic acid

The oxidative DNA damage by copper (II) complexes in the presence of chlorogenic acid was explored using agarose gel electrophoresis. The extent of pBR322 DNA damage was enhanced significantly with increasing concentration of [Cu-phen-Thr] complex and incubation time. A fluorescence quenching activity of calf thymus DNA–EB was observed more remarkably with chlorogenic acid than without chlorogenic acid. The fluorescence measurements suggested that [Cu-phen-Thr] complex not only can bind to DNA by intercalation but also can damage the double strand DNA in the presence of chlorogenic acid. Further, 8-hydroxy-2′-deoxyguanosine, a biomarker of DNA oxidative damage was determined by electrochemical method. The control experiments revealed that the structure of copper (II) complexes affected capability of complex to DNA damage. The planar structure copper (II) complex showed high efficiency to DNA damage. The chlorogenic acid as biological reductant could improve copper (II) complex to DNA damage. A mechanism on [Cu-phen-Thr] complex to DNA damage in the presence of chlorogenic acid was proposed.     

Synthesis and DNA binding of mu-[2,9-bis(2-imidazo[4,5-f][1,10]phenanthroline)-1,10-phenanthroline]bis[1,10-phenanthrolinecopper(II)

A binuclear complex [(phen)Cu(mu-bipp)Cu(phen)](ClO(4))(4), where phen=1,10-phenanthroline and bipp=2,9-bis(2-imidazo[4,5-f][1,10]phenanthroline)-1,10-phenanthroline, has been synthesized and its interaction with calf-thymus DNA in the buffer containing 5mM Tris and 50mM NaCl has been studied by means of electronic absorption titration, luminescence titration and viscometric measurements. The absorbance of the complex in the range of 320-400 nm, which is mainly based on bipp showed no obvious change upon addition of DNA, while the peak at 270 nm, which is determined by both phen and bipp decreased by up to 18%. The emission band of the complex around 360 nm decreased remarkably in presence of DNA. The emission quenching of this complex by [Fe(CN)(6)](4-) was depressed greatly when bound to DNA. The relative viscosity of DNA was increased by this complex more significantly than a bipp directed intercalating reagent. These results suggest that this complex binds to calf thymus DNA by intercalation of the two phenanthrolinecopper terminals. The apparent intrinsic binding constant of the complexes with DNA was 1.6 x 10(4)M(-1) as determined by UV-visible titration.     

A novel cytotoxic ternary copper(II) complex of 1,10-phenanthroline and L-threonine with DNA nuclease activity

A novel ternary copper(II) complex, [Cu(phen)(L-Thr)(H2O)](ClO4) (phen=1,10-phenanthroline, L-Thr=L-threonine), has been synthesized and structurally characterized. The complex crystallized in a triclinic system with space group P1 , a=7.526(15) A, b=11.651(2) A, c=12.127(2) A, alpha=115.41(3) degrees , beta=102.34(3) degrees and gamma=91.33(3) degrees . The copper(II) center is situated in a distorted square-pyramidal geometry. At a concentration of 10(-6) mol L(-1), the complex exhibited potent cytotoxic effects against human leukemia cell line HL-60 and human stomach cancer cell line SGC-7901 with inhibition rates of over 90%, however, less pronounced effects were observed for human liver carcinoma cell line BEL-7402 and human non-small-cell lung cancer cell line A-549. The complex was shown to bind DNA by intercalation and cleave pBR322 DNA in the presence of ascorbate.     

Synthesis, characterization, and DNA binding and cleavage properties of copper(II)-tryptophanphenyl-alanine-1,10-phenanthroline/2,2'-bipyridine complexes

The mononuclear dipeptide‐based Cu^II complexes [Cu^II(trp‐phe)(phen)(H₂O)] ⋅ ClO₄ ( 1 ) and [Cu^II(trp‐phe)(bpy)(H₂O)] ⋅ ClO₄ ( 2 ) (trp‐phe=tryptophanphenylalanine, phen=1,10‐phenanthroline, bpy=2,2′‐bipyridine) were isolated, and their interaction with DNA was studied. They exhibit intercalative mode of interaction with DNA. The intercalative interaction was quantified by Stern Volmer quenching constant (K_sq=0.14 for 1 and 0.08 for 2 ). The Cu^II complexes convert supercoiled plasmid DNA into its nicked circular form hydrolytically at physiological conditions at a concentration as low as 5 μM (for 1 ) and 10 μM (for 2 ). The DNA hydrolysis rates at a complex concentration of 50 μM were determined as 1.74 h⁻¹ (R=0.985) for 1 and 0.65 h⁻¹ (R=0.965) for 2 . The rate enhancement in the range of 2.40–4.10×10⁷‐fold compared to non‐catalyzed double‐stranded DNA is significant. This was attributed to the presence of a H₂O molecule in the axial position of the Cu complexes.     

Binding and oxidative cleavage studies of DNA by mixed ligand Co(III) and Ni(II) complexes of quinolo [3,2-b]benzodiazapine and 1,10-phenanthroline

Two mixed ligand complexes of the type [M(phen)(2)(qbdp)](PF(6))n.xH(2)O where M = Co(III) and Ni(II), qbdp = quinolo[3,2-b] benzodiazepine and phen = 1,10-phenanthroline, n = 3 or 2, x = 2 or 3 have been synthesized and characterized by employing analytical and spectral methods. The DNA binding property of the complexes with calf thymus-DNA has been investigated by using absorption spectra, viscosity measurements as well as thermal denaturation studies. The absorption spectral results indicate that the Co(III) and Ni(II) complexes intercalate between the base pairs of the DNA tightly with intrinsic DNA binding constant of 6.4 x 10(4) and 4.8 x 10(4) M(-1) in Tris HCl buffer containing 50 mM NaCl, respectively. The large enhancement in the relative viscosity of DNA on binding to the quinolo [3,2-b] benzodiazepine supports the proposed DNA binding modes. The complexes on reaction with super coiled (SC) DNA shows nuclease activity.     

Chemical speciation of ternary complexes of L-dopa and 1,10-phenanthroline with Co(II), Ni(II) and Cu(II) in low dielectric media

Abstract

A computer assisted pH-metric investigation has been carried out on the speciation of complexes of Co(II), Ni(II) and Cu(II) with L-dopa and 1,10-phenanthroline. The titrations were performed in the presence of different relative concentrations (M:L:X = 1.0:2.5:2.5; 1.0:2.5:5.0; 1.0:5.0:2.5) of metal (M) to L-dopa (L) and 1,10-phenanthroline (X) with sodium hydroxide in varying concentrations (0-60% v/v) of 1,2-propanediol-water mixtures at an ionic strength of 0.16 mol L^-1 and at a temperature of 303.0 K. Stability constants of the ternary complexes were refined using MINIQUAD75. The species MLXH, MLX, ML₂X and MLX₂H for Co(II) and Cu(II) and MLXH, MLX and MLX₂H for Ni(II) were detected. The extra stability of ternary complexes compared to their binary complexes was believed to be due to electrostatic interactions of the side chains of ligands, charge neutralisation, chelate effect, stacking interactions and hydrogen bonding. The species distribution with pH at different compositions of 1, 2-propanediol-water mixtures and plausible equilibria for the formation of species were also presented. The bioavailability of the metal ions is explained based on the speciation.     

Sequence specificity of DNA cleavage by bis(1,10-phenanthroline)copper(I)

The bis(1,10-phenanthroline)copper(I) complex is a relatively simple molecule previously shown to cause DNA cleavage with a strong preference for gene control regions such as the Pribnow box. Sequence level mapping of sites of [(Phen)2CuI]+ cleavage in greater than 2000 bases in histone genes and the plasmid pUC9 showed that the specificity for control regions is related to a predominant preference for minor groove binding at TAT triplets, which were cleaved most strongly at the adenosine sugar ring. The related sequences TGT, TAAT, TAGPy, and CAGT (Py = pyrimidine) were moderately preferred, while CAT and TAC triplets, PyPuPuPu quartets, PuPuPuPy quartets, and CG-rich PyPuPuPy quartets were cleaved with low to average frequency. Polypurine and polypyrimidine sequences were cleaved with low frequency. The sequence preferences of [(Phen)2CuI]+ can be ascribed predominantly to (i) a requirement for binding in the minor groove at a pyrimidine 3'----5' step and (ii) stereoelectronic effects of the 2-amino group of guanine in the minor groove, which inhibit binding. Although the reagent appears primarily to recognize sequence features at the triplet or quartet level, lower than expected cleavage was observed for two TAT sequences adjacent to several other preferred sequences and higher than expected cleavage was observed at CAAGC sequences, suggesting that longer range sequence-dependent DNA conformational effects influence specificity in certain cases.     

Noncovalent DNA binding of bis(1,10-phenanthroline)copper(I) and related compounds

The noncovalent DNA binding of the bis(1,10-phenanthroline)copper(I) complex [(Phen)2CuI] was examined under anaerobic conditions by absorption and circular dichroism spectroscopy, and viscometry, as a function of phenanthroline concentration. Analyses according to the McGhee-von Hippel method indicated that binding exhibited both neighbor-exclusion and positive cooperativity effects, with a neighbor-exclusion parameter n approximately 2 and a cooperativity parameter omega approximately 4. The association constant for (Phen)2CuI binding decreased with increasing concentration of phenanthroline in excess over that required to stoichiometrically generate (Phen)2CuI, indicating that free phenanthroline was a weak competitive inhibitor of (Phen)2CuI binding. The maximal association constant for DNA binding of (Phen)2CuI in 0.2 M NaCl and 9.8% ethanol, extrapolated to zero concentration of excess phenanthroline, was 4.7 x 10(4) M-1 (DNA base pairs). The magnitude of the neighbor-exclusion parameter, the changes in spectral properties of (Phen)2CuI induced by DNA binding, and the increase in DNA solution viscosity upon (Phen)2CuI addition are consistent with a model for DNA binding by (Phen)2CuI involving partial intercalation of one phenanthroline ring of the complex between DNA base pairs in the minor groove as suggested previously [Veal & Rill (1989) Biochemistry 28, 3243-3250]. Viscosity measurements indicated that the mono(phenanthroline)copper(I) complex also binds to DNA by intercalation; however, no spectroscopic or viscometric evidence was found for DNA binding of free phenanthroline or the bis(2,9-dimethyl-1,10-phenanthroline)copper(I) complex. DNA binding of free phenanthroline may be cooperative and induced by prior binding of (Phen)2CuI.