Copper complexes of two isomeric NS2-macrocycles

Two isomeric NS₂-macrocycles incorporating a xylyl group at ortho (o -L) and meta (m -L) positions were employed and their copper complexes (1?C5) were prepared and structurally characterized. The copper(II) nitrate complexes [Cu(L)(NO₃)₂] (1: L = o -L, 2: L = m -L) for both ligands were isolated. In each case, the copper center is five-coordinated with a distorted square pyramidal geometry. Despite the overall geometrical similarity, 1 and 2 show the different ligand conformation due to the discriminated packing pattern. Reaction of o -L with copper(II) perchlorate afforded complex 3 containing two independent complex cations [Cu(o -L)(H₂O)(DMF)(ClO₄)]⁺ and [Cu(o -L)(H₂O)(DMF)]²⁺; the coordination geometry of the former is a distorted octahedron while the latter shows a distorted square pyramidal arrangement. In the reactions of copper(I) halides (I or Br), o -L gave a mononuclear complex [Cu(o-L)I] (4) with a distorted tetrahedral geometry, while m -L afforded a unique exodentate 2:1 (ligand-to-metal) complex [trans-Br₂Cu(m-L)₂] (5) adopting a trans-type square-planar arrangement.     

Synthetic and mechanistic investigation of piperonyl butoxide from dihydrosafrole

Piperonyl butoxide (PBO) 1 was prepared via the successive chloromethylation and etherification of dihydrosafrole 3. In this work, during the chloromethylation of 3, several by-products such as 5 (the isomer of chloromethyldihydrosafrole 4), 6-propylpiperonyl alcohol 6, bis(chloromethyl)-dihydrosafrole 7 and 8, bis(2-propyl-4,5-methylenedioxyphenyl)methane 9 and di(2-propyl-4,5-methy lene-dioxybenzyl)ether 10 were found. However, it was found that 5, 6, 7, and 8 could undergo a further reaction to the final product (PBO), rather than its derivatives, though the by-products 9 and 10 still existed. Based on these results, the plausible mechanism of the chloromethylation and etherification of 3 was proposed. Furthermore, the reliability of the plausible mechanism was verified by quantum chemical calculations using DFT. In addition, the final product (PBO) was produced with a high selectivity and yield by reducing the by-products 9 and 10.     

Divalent Pb(0) compounds

Density functional theory (DFT) calculations have been carried out on four novel dicoordinated lead compounds PbL₂ where L is an N-heterocyclic ylidene or a five-membered cyclic ylidene (1Pb, 2Pb, 4Pb, 5Pb) and for a plumbylene-coordinated carbone CL₂ (3Pb). The theoretically predicted equilibrium geometries and the first and second proton affinities of 1Pb?C5Pb are reported. Geometry optimizations have also been carried out for the complexes with one and two BH₃ ligands 1Pb(BH ₃ )?C5Pb(BH ₃ ) and 1Pb(BH ₃ ) ₂ ?C5Pb(BH ₃ ) ₂ , and for the transition metal complexes 1PbW(CO) ₅ ?C5PbW(CO) ₅ and 1PbNi(CO) ₃ ?C5PbNi(CO) ₃ . The results suggest that the molecules 1Pb, 2Pb and 4Pb possess properties which identify them as divalent Pb(0) compounds (plumbylones). This comes to the fore by the theoretically predicted second PAs which are very large for a lead compound and (for 1Pb and 4Pb) by the BDE of the second BH₃ ligand. Compound 3Pb should be considered as a plumbylene-coordinated divalent C(0) compound (carbone) which has a very high second PA of 195.1?kcal/mol. The geometry optimization of 5Pb gives an equilibrium structure which identifies the molecules as divalent Pb(II) compound, i.e., as a plumbylene.     

Watson–Crick versus imidazopyridopyrimidine base pairs: theoretical study on differences in stability and hydrogen bonding strength

Matsuda and coworkers demonstrated that imidazopyridopyrimidine nucelobases (N ^N , O ^O , N ^O , tO ^O , and O ^N ) can mimic Watson–Crick nucleobase in forming H-bonds in DNA double helix. In the present study, we address the question about the strengths of the H-bonds in imidazopyridopyrimidine base pairs compared to those in Watson–Crick ones by focusing particularly on the nature of these interactions. Optimized structures of imidazopyridopyrimidine, imidazopyridopyrimidine–Watson–Crick, and Watson–Crick base pairs are obtained at the DFTB3LYP/6-311++G (d,p). The nature and strength of the intramolecular H-bonds in these base pairs have been investigated based on natural bond orbital (NBO method) to consider the effect of charge transfer, “atoms-in-molecules” (AIM) topological parameters, and decomposition of the interaction energies using the energy decomposition analysis (EDA). These investigations imply that N ^N –O ^O and N ^O –O ^N can form base pairs with four H-bonds (most stable than those of Watson–Crick base pairs) when they incorporated into DNA double helix. Furthermore, it can be deduced that O ^N and N ^N nucleobases form energetically more favorable pairs with adenine and guanine than the normal Watson–Crick counter parts. These results can be helpful for the stabilization and regulation of a variety of new base-pairing motif of DNA structures.     

Syntheses and spectroscopic characterization of double-armed benzo-15-crown-5 derivatives and their sodium and potassium complexes

A series of new benzo-15-crown-5 derivatives (1–6) containing formyl and imine groups were prepared. New formyl crown ethers (1 and 2) were prepared by reaction of 4′,5′-bis(bromomethyl)benzo-15-crown-5 with 2-hydroxy-3-methoxybenzaldehyde (o-vanillin) and 2-hydroxy-5-methoxybenzaldehyde in the presence of NaOH. New Schiff bases (3–6) were synthesized by the condensation of corresponding aldehydes with 1,3-diaminopropane and 1,4-diaminobutane. Sodium and potassium complexes (1a–6a and 1b–6b) of the crown compounds forming crystalline complexes of 1:1 (Na⁺:ligand) and 1:2 (K⁺:ligand) stoichiometries were also synthesized. The structures of the aldehydes 1 and 2, imines 3–6 and complexes (1a–3a and 1b–3b) were confirmed on the basis of elemental analyses, IR, ¹H- and ¹³C-NMR, and mass spectroscopy.     

Spin-spin interaction between phenyl nitroxides through the σ-π system

The spin states of a series of silicon- and carbon-bridged phenyl nitroxides were examined with respect to the temperature dependent ESR and SQUID measurements. Of those, a linear relationship between the ESR signal intensity and 1/T (T = absolute temperature) and an increase of χ_molT along lowering T were observed for a compound having disilanylene-bridged m- and p-phenyl nitroxide units (Si2mp), indicating ferromagnetic spin-spin interaction in this molecule. In contrast to this, no clear intramolecular spin-spin interaction took place in the monosilanylene analogue (Si1mp). Mono- and disilanylene-bridged phenylnitroxides with p-, p- or m-, m-substitution (Si1pp,Si1mm, Si1pp, and Si2mm) exhibited the singlet ground state. The trisilanylene and siloxanylene bridges did not play an obvious role in the spin interaction, in either a ferro- or antiferromagnetic fashion, regardless of the substitution modes of the phenylenes. MO calculations on the model compounds provided a mechanistic interpretation for the high-spin interaction through the σ-π system.     

Resonance in compounds with multiple conjugated bonds

The resonance of the compounds buta-1,3-diyne (1), buta-1,3-diene (2), hexa-1,3,5-triyne (3), hexa-1,3,5-triene (4), hexa-3-en-1,5-diyne (5), and hexa-1,5-dien-3-yne (6) was analyzed. The molecular geometry, π molecular orbitals, and the electron density of these compounds were analyzed. The NBO, AIM, and NRT methods were used. By comparing the electronic structures of compounds 1 and 2 and by considering that the latter is a classic example of a π-conjugated compound (Org Lett 5:2373–2375, 2003; Org Lett 5:2373–2375, 2004), it was possible to conclude that the conjugation of compound 1 is larger than that of 2. Compounds 3 and 4 were also studied, in order to understand the effect of a longer conjugated chain, and it was found that the resonance also increases in the case of 3. In addition, the effect of changing the order of the central bond was investigated by comparison of compounds 5 and 6 with 3 and 4, respectively. The results indicated that changes produce small alterations in the properties of compounds 3 and 4.     

How do phosphoramides compete with phosphine oxides in lanthanide complexation? Structural, electronic and energy aspects at ab initio and DFT levels

Novel comparison of the structural, electronic and energy aspects of lanthanide complexes of model phosphoramides (PAs) with those of phosphine oxides (POs), phosphate esters (PEs) and phosphoryl trihalides (PHs) has been carried out by ab initio and DFT calculations. Atoms in Molecules (AIM) and Natural Bonding Orbital (NBO) analyses were performed to understand the electronic structure of ligands L and related complexes, L–Ln³⁺. NBO analysis indicates that the negative charge on phosphoryl oxygen (O_P) and the p character of the phosphoryl lone pair, Lp(O_P), increase in the order PH < PE < PO < PA. Positive charge of the lanthanide cation in PA complexes is less than those of PH, PE and PO complexes, due to the more intense ligand to metal charge transfer (LMCT). The metal–ligand distance decreases in the order PH > PE > PO > PA, which is confirmed by the results of AIM analysis. Charge density at the bond critical point of L–Ln³⁺ follows the sequence PH < PE < PO < PA. The results of the Energy Decomposition Analysis (EDA) indicate that the donative interaction and LMCT increases in order PH < PO < PE < PA. The effect of basis set superposition error (BSSE) on the L···Ln³⁺ interaction energies was also studied in detail at DFT, MP2 and CCSD(T) levels using the counterpoise (CP) method. Trends in the CP-corrected L–Ln³⁺ bond energies are in good accordance with the optimized O_P···Ln³⁺ distances. The results show that the difference between CP-corrected and uncorrected interaction energies in PA complexes is larger than those in the others, because PAs are more deformable. It is depicted that PAs are comparable with POs in lanthanide complexation.     

Dipyrrolylquinoxaline-bridged hydrazones: a new class of chemosensors for copper(II)

Novel 2,3-bis(1H-pyrrol-2-yl)quinoxaline-functionalized hydrazones were prepared and characterized as new chemosensors for copper(II) ion. The binding properties of the compounds 4, 5, 6 and 7 for cations were examined by UV–vis, fluorescence spectroscopy, and linear sweep voltammetric experiments (LSV). The results indicate that a 1:1 stoichiometric complex is formed between compound 4 (or 5, 6, 7) and copper(II) ion, and the association constant is 1.3?×?10⁵ M^?1 for 4, 2.1?×?10⁶ M^?1 for 5, 4.1?×?10⁵ M^?1 for 6 and 8.0?×?10⁵ M^?1 for 7, respectively. The recognition mechanism between compound 4 (or 5, 6, 7) and metal ion was discussed based on their electrochemical properties, absorbance changes, and the fluorescence quenching effect when they interact with each other. Control experiments revealed that compound 4 (or 5, 6, 7) has a highly selective response to copper (II) ion.     

Computational investigation of thermochemical properties of non-natural C-nucloebases: different hydrogen-bonding preferences for non-natural Watson–Crick base pairs

In the present density functional theory study, we have compared intrinsic properties of non-natural nucleobases (acA, acG, acC, and acT nucleobases) such as proton affinities, gas phase acidities, tautomerization, and hydrogen-bonding properties with those in normal Watson–Crick nucleobases (A, G, C, T nucleobases). The hydrogen-bonding interactions in non-natural and Watson–Crick base pairs were studied at B3LYP/6-311++G (d,p) level regarding their geometries, energies, and topological features of the electron density. The quantum theory of atoms-in-molecule (QTAIM) and natural bond orbital (NBO) analyses were employed to elucidate the interaction characteristics in base pairs. The electron density ρ(r) as well as its Laplacian $ \nabla^{2} $ ρ(r) at the hydrogen bond critical point predicted by QTAIM is strongly correlated with hydrogen bond structural parameter and the second-order perturbation energies in NBO scheme. Our results show that most of hydrogen bonds in normal Watson–Crick and non-natural base pairs must be considered as electrostatic interactions. Results of calculations revealed that energetic values of hydrogen bonds in T–A base pair are more than those in ac T–ac A base pair, while values of hydrogen bonds in C–G base pair and ac C–ac G base pair are almost the same. These results confirmed stability order of stabilization energies of these base pairs.     

Molecularly imprinted solid-phase extraction monolithic capillary column for selective extraction and sensitive determination of safranine T in wolfberry

A method was developed to sensitively determine safranine T in wolfberry by molecularly imprinted solid-phase extraction (MISPE) coupled with high-performance liquid chromatography and laser-induced fluorescence detection (HPLC-LIF). The MISPE capillary monolithic column was prepared by water-bath in situ polymerization, using safranine T, methacrylic acid (MAA), and ethylene dimethacrylate (EDMA) as template, functional monomer, and cross-linker, respectively. The properties of the homemade MISPE capillary monolithic column, including capacity and specificity, were investigated under optimized conditions and the morphologies of inner polymers were characterized by scanning electron microscopy (SEM). The mean recoveries of safranine T in wolfberry ranged from 91.2 % to 92.9 % and the intraday and interday relative standard deviation (RSD) values all ranged from 3.4 % to 4.2 %. Good linearity was obtained over 0.001–1.0 μg mL^–1 (r?=?0.9999) with a detection limit (S/N?=?3) of 0.4 ng g^–1. Under the selected conditions, enrichment factors of over 90-fold were obtained and the extraction on the monolithic column effectively cleaned up the wolfberry matrix. The results demonstrated that the proposed MISPE-HPLC-LIF method could be applied to sensitively determine safranine T in wolfberry.

Synthese,Kristallstruktur und Konformation vontrans-[2.2](1,2)Ferrocenophan und seinen 1-Hydroxyderivaten

Starting from1-(dimethylaminomethyl)-2-iodo-ferrocene (3) [2.2](1,2)ferrocenophane (2) was prepared in an 8-step synthesis with 17% overall yield. Both from the oxoderivative12 and the ferrocenophane2 puretrans-isomers (12b and2b, resp.) were obtained; the former (12b) was reduced to a separable mixture ofexo andendo 1-hydroxy-ferrocenophanes13a andb, resp. (～ 3:7), the configurations of which were assigned by the LIS-method. X-ray crystal structure analysis of2b revealed a centrosymmetrical chair conformation. From¹H- and¹³C-NMR spectra both for2b and for the hydroxyderivatives13 a rigidexo-exo chair conformation was deduced.     

Synthesis and characterization of benzothiazol-2-one derivatives as anti-inflammatory and analgesic agents

A series of new compounds bearing a 1,3-benzothiazol-2-one nucleus have been synthesized using 5,6-dimethyl-3-(2-oxo-propyl)-1,3-benzothiazol-2-one (1) as a key starting compound. The reaction of 1 with some nucleophilic compounds led to the formation of compounds 2, 3, 4, 5a, b, 6 and 7a, b. The thiosemicarbazone derivatives 7a, b were treated with a number of halo ketones to produce the new heterocyclic compounds 9–13, while their reaction with acid anhydrides led to the formation of the derivatives 14 and 15. Also, compound 1 was condensed with different aromatic aldehydes to afford the corresponding chalcones 18–22. The structures of all the novel compounds have been determined by analytical and spectral data. Some of the compounds were selected to be evaluated as anti-inflammatory and analgesic agents.     

Synthesis, X-ray structural analysis, and cytotoxic activity of some new androstane d-homo lactone derivatives

A series of d-homo lactones 4?C10 from dehydroepiandrosterone 1 via 16-hydroximino derivatives 2 and 3 were synthesized. The d-homo lactone 4 was transformed by the Oppenauer oxidation to obtain compound 5. The (Z)-2-hydroxymethylene-4-en-3-one compound 6, was obtained through reaction of 4-en-3-one compound 5 with ethyl formate and sodium hydride. The epoxides 8 and 9 were prepared from compound 7 by oxidation with m-chloroperbenzoic acid. Compound 10 was obtained by treating epoxides 8 and 9 with chromium(VI)-oxide. The structure of compounds 6 and 10 were confirmed by X-ray structural analysis. These derivatives were screened for antitumor activity against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER?, MDA-MB-231, prostate cancer AR?, PC-3), and one human non-tumor cell line, MRC-5. Compounds 4, 7, 8, and 10 exhibited significant antitumor activity against MDA-MB-231 cells, while compound 5 showed strong cytotoxicity against MDA-MB-231. No compounds displayed toxicity against MRC-5 cells.     

Zur Chemie der 5-Alkylamino-4H-thiopyrano[2,3-b]pyridin-4-one

4-Alkylaminopyridinethiones · HCl (1 · HCl) react with bis-trichlorethylmalonate (3) predominantly to 5-alkylamino-4H-thiopyrano [2,3-b]pyridine-4-ones (6). With alcohols in the presence of acids at 25°C6 undergoes an alcoholysis to the corresponding alkyl-3-(2-thioxo-3-pyridyl)propionates (9). On heating in dilute alkali6 is hydrolysed via 4-alkylamino-2-thioxopyridyl-propylketones (11) to the tautomers, 4-hydroxy-2-thioxopyridylpropylketone (12 A) and 2-thioxo-3-(1-hydroxybutenyl)-4-piperidon (12 B), resp. On refluxing with alkali the ethyl-pyridylpropionate9 a is cyclisized to the 1-alkyl-1,6-naphthyridine-2(1H)-one (4 a), but boiling in ethanolic acid hydrolyses9 a via the pyridylpropionic acid10 to 4-alkyl-aminopyridylpropylketone (11 a). The latter can be transformed via the tautomers12 A,B and 2-methylthio-3-pyridylpropylketone (13) to the 4-hydroxy-3-butyrylpyridone (14 A) and its tautomer, 3-(1-hydroxy-butenyl)-piperidine-2,4-diones (14 B) resp. The structure of14 A,B is established by reaction of 4-isopropylamino-2(1H)-pyridone (2) with butanoylchloride to the 4-isopropylamino-3-butyrypyridone (15) and hydrolysis of15 to the tautomers14 A,B.     

Autoassembly of cage structures

Thed,l-(1a) andmeso-forms (1b) of α,α'-dihydroxy-α,α'-dimethyladipic acid, dilactone (3), diiminodilactone (4), and lactonolactam (5) were obtained by the reaction of acetonylacetone with KCN and HCl. The transformations of1 to the esters2, dilactone3 to la, and diiminodilactone4 to dilactone3 were studied. It was shown that3 can be readily obtained from la by thermolysis, acid catalysis, and DCC action as well as by acid catalyzed cyclization of2a, while dilactone3 can be obtained from1b and2b in negligible yield only under drastic conditions, obviously, due to the partial epimirization of themeso-forms. The mild thermolysis of1b leads totrans-lactonoacid (6), from which the ester7 has been obtained. The effective acid catalyzed cyclization of amides8 and9 to3, lactamoamide12 to5, and amide14 to model lactone13 was found. The NMR spectra of the products were studied, and a¹H NMR test was suggested for identification ofd,l- andmeso-forms1 and2. The stereochemistry of monolactones6, 7, 9, 10a, 10b, 11, and dilactone3 was established. The differences in the chemical behavior of α,α'-dihydroxyglutaric and adipic acids were explained by the significant reduction of the non-bonded interactions of the substituents in the corresponding monolactones during the transfer from 1,3- to 1,4-substituted systems.     

Synthesis of some fused heterocyclic systems and their nucleoside candidates

A series of pyridofuro compounds were synthesized from 4-(4-chlorophenyl)-1,2-dihydro-2-oxo-6-(thiophen-2-yl)pyridine-3-carbonitrile (1) as starting material. Alkylation of 1 with ethyl bromoacetate gave the corresponding ester 2, which was condensed with hydrazine hydrate to afford the corresponding acid hydrazide derivative 3. Thrope-Ziegler cyclization of 2 with sodium methoxide gave furo[2,3-b]pyridine derivative 4, which was reacted with thiosemicarbazide, allyl isothiocyanate, formamide or hydrazine hydrate to give furopyridine derivatives 5–8, respectively. The latter compound 8 was cyclized with acetylacetone or formic acid to give the corresponding compounds 9 and 10, respectively. Furthermore, sulfurization of 1 with P₂S₅ gave the corresponding thioxopyridine 11, which was reacted with glycosyl (or galactosyl) bromide, morpholine or piperidine to give the corresponding thioglycoside 12a,b and Mannich base 14a,b derivatives. The deacetylation of 12a,b gave the corresponding deacetylated thioglycosides 13a,b, respectively. All the newly synthesized compounds were characterized by the elemental analyses and spectroscopic evidences (IR, ¹H- and ¹³C NMR).     

Tri- and tetraphenylantimony propiolates: Syntheses and structures

The reaction of triphenylantimony with propiolic acid in the presence of hydrogen peroxide (molar ratios 1 : 2 : 1 and 1 : 1 : 1) in diethyl ether affords triphenylantimony dipropiolate Ph₃Sb[OC(O)C≡CH]₂ (I) and μ₂-oxobis[(propiolato)triphenylantimony] [Ph₃SbOC(O)C≡CH]₂O (II). Tetraphenylantimony propiolate Ph₄SbOC(O)C≡CH (III) is synthesized from pentaphenylantimony and propiolic or acetylenedicarboxylic acid in toluene. According to the X-ray diffraction data, the crystals of compounds I and III include two types of crystallographically independent molecules (a and b). The antimony atoms in molecules Ia, Ib, II, IIIa, and IIIb have the trigonal-bipyramidal coordination mode with different degrees of distortion. The OSbO and OSbC axial angles are 176.8(2)° (Ia, Ib), 170.17(15)°, 178.78(14)° (II), and 173.2(5)°, 174.4(5)° (IIIa, IIIb). The CSbC equatorial angles lie in the ranges 108.2(3)°–143.1(3)° (I), 109.0(2)°–131.0(2)° (II), and 113.1(4)°–125.4(4)° (III). The SbOSb angle in II is 141.55(19)°. The Sb-C bond lengths are 2.103(8)–2.141(5) (I), 2.105(5)–2.119(5) (II), and 2.076(12)–2.166(13) Å (III). The Sb-O distances increase in a series of I, II, and III: 2.139(6)–2.156(7) (Ia, Ib); 2.206(4), 2.218(3) (II); and 2.338(10), 2.340(10) Å (III).     

Zur Kenntnis der Struktur der Chalkon-Guanidin-Kondensate Über Heterocyclen, 75. Mitt.

Guanidine reacts with chalkone1 a, 4-methylchalkone1 b and 4′-methylchalkone1 c resp. to yield mixtures of pyrimidinamines2 a,3 b and3 c (=3 b) resp. with (2:1)-condensatesA,B andC resp. The structures of the compoundsA-C (whicha priori could be dihydropyrimidopyrimidines4 a-c or5 a-c or6 a-c) are elucidated. NMR-investigations show that the saltsA-C · HCl must be symmetrically substituted pyrimidopyrimidinyliumchlorides4 a-c · HCl or5 a-c · HCl (and not6 a-c · HCl). Furthermore, it is proved by chemical methods that the condensatesB · HCl andC · HCl are pyrimidopyrimidinyliumchlorides4 b andc · HCl (and not5 b andc · HCl): The structure ofB · HCl (=4 b · HCl) was established by total synthesis of dimethylpyrimidopyrimidinyliumpicrate9 b-Pi from10 c (via13 c · HI-18 · HCl) and transformation ofB · HCl into an identical salt9 b-Pi via hexahydropyrimidopyrimidine8 b · HCl. The structure ofC · HCl (=4 c · HCl) was determined by comparison of its hydrogenation product (=8c · HCl) with8 b · HCl. The structure of condensateA · HCl (=4 a · HCl) results from conclusion by analogy. The spatial structure of4 a-c · HCl and8 a-c · HCl is discussed; it was established by NMR that the salts are racemic mixtures of stereoisomers4 a-c K · HCl and8 a-c K · HCl resp. and their antipodes (with C₂ symmetry).     

Competitive Binding Sites of a Ruthenium Arene Anticancer Complex on Oligonucleotides Studied by Mass Spectrometry: Ladder-Sequencing versus Top-Down

We report identification of the binding sites for an organometallic ruthenium anticancer complex [(η ⁶-biphenyl)Ru(en)Cl][PF₆] (1; en = ethylenediamine) on the 15-mer single-stranded oligodeoxynucleotides (ODNs), 5′-CTCTCTX₇G₈Y₉CTTCTC-3′ [X = Y = T (I); X = C and Y = A (II); X = A and Y = T (III); X = T and Y = A (IV)] by electrospray ionization mass spectrometry (ESI-MS) in conjunction with enzymatic digestion or tandem mass spectrometry (top-down MS). ESI-MS combined with enzymatic digestion (termed MS-based ladder-sequencing), is effective for identification of the thermodynamically-favored G-binding sites, but not applicable to determine the thermodynamically unstable T-binding sites because the T-bound adducts dissociate during enzymatic digestion. In contrast, top-down MS is efficient for localization of the T binding sites, but not suitable for mapping ruthenated G bases, due to the facile fragmentation of G bases from ODN backbones prior to the dissociation of the phosphodiester bonds. The combination of the two MS approaches reveals that G₈ in each ODN is the preferred binding site for 1, and that the T binding sites of 1 are either T₇ or T₁₁ on I and IV, and either T₆ or T₁₁ on II and III, respectively. These findings not only demonstrate for the first time that T-bases in single-stranded oligonucleotides are kinetically competitive with guanine for such organoruthenium complexes, but also illustrate the relative merits of the combination of ladder-sequencing and top-down MS approaches to elucidate the interactions of metal anticancer complexes with DNA.