Simultaneous binding of meso-tetrakis(N-methylpyridinium-4-yl)porphyrin and 4',6-diamidino-2-phenylindole at the minor grooves of poly(dA).poly(dT) and poly[d(A-T)(2)]: fluorescence resonance energy transfer between DNA bound drugs

The spectral properties of meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (TMPyP) bound to poly(dA).poly(dT) and poly[d(A-T)(2)] in the presence and in the absence of 4',6-diamidino-2-phenylindole (DAPI) have been studied. DAPI fits deeply into the minor groove of both poly(dA).poly(dT) and poly[d(A-T)(2)], and TMPyP is also situated at the minor groove. The nature of the absorption, circular dichroism (CD), and flow linear dichroism (LD) spectra of the TMPyP-poly(dA).poly(dT) and -poly[d(A-T)(2)] complexes in the Soret band is essentially unaffected whether the minor groove is blocked by DAPI or not, although small variations been noticed in the presence of DAPI. Furthermore, a close analysis of the reduced LD spectrum in the Soret band results in angles of approximately 80 degrees and 55 degrees between transition moments of the TMPyP and DNA helix axes in the absence of DAPI. All these observations indicate that the side of TMPyP whose structure resembles that of classical minor groove binding drugs does not fit deeply into the minor groove. This suggests that TMPyP binds across the minor groove: two positively charged pyridiniumyl rings interact electrostatically with negatively charged phosphate groups of DNA. When DAPI and TMPyP are simultaneously bound to poly(dA).poly(dT) or poly[d(A-T)(2)], the fluorescence intensity of DAPI decreases as TMPyP concentration increases, indicating that the excited energy of DAPI is transferred to TMPyP.     

Stabilization by extra-helical thymines of a DNA duplex with Hoogsteen base pairs

We present the crystal structure of the DNA duplex formed by d(ATATATCT). The crystals contain seven stacked antiparallel duplexes in the asymmetric unit with A.T Hoogsteen base pairs. The terminal CT sequences bend over so that the thymines enter the minor groove and form a hydrogen bond with thymine 2 of the complementary strand in the Hoogsteen duplex. Cytosines occupy extra-helical positions; they contribute to the crystal lattice through various kinds of interactions, including a unique CAA triplet. The presence of thymine in the minor groove apparently contributes to the stability of the DNA duplex in the Hoogsteen conformation. These observations open the way toward finding under what conditions the Hoogsteen duplex may be stabilized in vivo. The present crystal structure also confirms the tendency of A.T-rich oligonucleotides to crystallize as long helical stacks of duplexes.     

A third mode of DNA binding: Phosphate clamps by a polynuclear platinum complex

We describe a 1.2 A X-ray structure of a double-stranded B-DNA dodecamer (the Dickerson Dodecamer, DDD, [d(CGCGAATTCGCG)]2) associated with a cytotoxic platinum(II) complex, [{trans-Pt(NH3)2(NH2(CH2)6(NH3+)}2-mu-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}] (TriplatinNC). TriplatinNC is a multifunctional DNA ligand, with three cationic Pt(II) centers, and directional hydrogen bonding functionalities, linked by flexible hydrophobic segments, but without the potential for covalent interaction. TriplatinNC does not intercalate nor does it bind in either groove. Instead, it binds to phosphate oxygen atoms and thus associates with the backbone. The three square-planar tetra-am(m)ine Pt(II) coordination units form bidentate N...O...N complexes with OP atoms, in a motif we call the Phosphate Clamp. The geometry is conserved among the 8 observed phosphate clamps in this structure. The interaction appears to prefer O2P over O1P atoms (frequency of interaction is O2P > O1P, base and sugar oxygens > N). The high repetition and geometric regularity of the motif suggests that this type of Pt(II) center can be developed as a modular nucleic acid binding device with general utility. TriplatinNC extends along the phosphate backbone, in a mode of binding we call "Backbone Tracking" and spans the minor groove in a mode of binding we call "Groove Spanning". Electrostatic forces appear to induce modest DNA bending into the major groove. This bending may be related to the direct coordination of a sodium cation by a DNA base, with unprecedented inner-shell (direct) coordination of penta-hydrated sodium at the O6 atom of a guanine.     

Duplex-promoted platination of adenine-N3 in the minor groove of DNA: challenging a longstanding bioinorganic paradigm

The interactions of [Pt(en)Cl(ACRAMTU-S)](NO3)2 (PT-ACRAMTU, en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) with adenine in DNA have been studied using a combination of analytical and high-resolution structural methods. For the first time, a cytotoxic platinum(II) complex has been demonstrated to form adducts in the minor groove of DNA through platination of the adenine-N3 endocyclic nitrogen. An acidic depurination assay was developed that allowed the controlled and selective (pH 2, 60 degrees C, 12 h) release of platinum-modified adenine from drug-treated nucleic acid samples. From the digested mixtures, three adducts were isolated by semipreparative reverse phase high-performance liquid chromatography and studied by electrospray ionization mass spectrometry (in-line LC-MS), variable-pH 1H NMR spectroscopy, and, where applicable, X-ray crystallography. The three species were identified as the N7 (A-I), N3 (A-II), and N1 (A-III) linkage isomers of [Pt(en)(ACRAMTU-S)(adenine)]3+ (A). Incubations carried out with the single- and double-stranded model sequences, d(TA)5 and d(TA)15, as well as native DNA indicate that the adduct profiles (A-I:A-II:A-IIIratios) are sensitive to the nature of the nucleic acid template. A-II was found to be a double-strand specific adduct. The crystal structure of this adduct has been determined, providing ultimate evidence for the N3 connectivity of platinum. A-II crystallizes in the triclinic space group P in the form of centrosymmetric dimers, {[Pt(en)(ACRAMTU-S)(adenine-N3)]2}6+. The cations are stabilized by a combination of adenine-adenine base pairing (N6...N1 2.945(5) A) and mutual acridine-adenine base stacking. Tandem mass spectra and 1H chemical shift anomalies indicate that this type of self-association is not merely a crystal packing effect but persists in solution. The monofunctional platination of adenine at its N7, N3, and N1 positions in a significant fraction of adducts breaks a longstanding paradigm in platinum-DNA chemistry, the requirement for nucleophilic attack of guanine-N7 as the principal step in cross-link formation. The biological consequences and potential therapeutic applications of the unique base and groove recognition of PT-ACRAMTU are discussed.     

2.4 A crystal structure of an oxaliplatin 1,2-d(GpG) intrastrand cross-link in a DNA dodecamer duplex

(1R,2R-Diaminocyclohexane)oxalatoplatinum(II) (oxaliplatin) is a third-generation platinum anticancer compound that produces the same type of inter- and intrastrand DNA cross-links as cisplatin. In combination with 5-fluorouracil, oxaliplatin has been recently approved in Europe, Asia, and Latin America for the treatment of metastatic colorectal cancer. We present here the crystal structure of an oxaliplatin adduct of a DNA dodecanucleotide duplex having the same sequence as that previously reported for cisplatin (Takahara, P. M.; Rosenzweig, A. C.; Frederick, C. A.; Lippard, S. J. Nature 1995, 377, 649-652). Pt-MAD data were used to solve this first X-ray structure of a platinated DNA duplex derived from an active platinum anticancer drug other than cisplatin. The overall geometry and crystal packing of the complex, refined to 2.4 A resolution, are similar to those of the cisplatin structure, despite the fact that the two molecules crystallize in different space groups. The platinum atom of the [Pt(R,R-DACH)](2+) moiety forms a 1,2-intrastrand cross-link between two adjacent guanosine residues in the sequence 5'-d(CCTCTGGTCTCC), bending the double helix by approximately 30 degrees toward the major groove. Both end-to-end and end-to-groove packing interactions occur in the crystal lattice. The latter is positioned in the minor groove opposite the platinum cross-link. A novel feature of the present structure is the presence of a hydrogen bond between the pseudoequatorial NH hydrogen atom of the (R,R)-DACH ligand and the O6 atom of the 3'-G of the platinated d(GpG) lesion. This finding provides structural evidence for the importance of chirality in mediating the interaction between oxaliplatin and duplex DNA, calibrating previously published models used to explain the reactivity of enantiomerically pure vicinal diamine platinum complexes with DNA in solution. It also provides a new kind of chiral recognition between an enantiomerically pure metal complex and the DNA double helix.     

Face-to-face and edge-to-face pi-pi interactions in a synthetic DNA hairpin with a stilbenediether linker

Synthetic conjugates possessing bis(2-hydroxyethyl)stilbene-4,4'-diether linkers (Sd2) form the most stable DNA hairpins reported to date. Factors that affect stability are length and flexibility of the linkers and pi-stacking of the stilbene moiety on the adjacent base pair. The crystal structure of the hairpin d(GT(4)G)-Sd2-d(CA(4)C) was determined at 1.5 A resolution. The conformations of the two molecules in the asymmetric unit differ both in the linker and the stem portions. One of them shows a planar stilbene that is stacked on the adjacent G:C base pair. The other displays considerable rotation between the phenyl rings and an unprecedented edge-to-face orientation of stilbene and base pair. The observation of considerable variations in the conformation of the Sd moiety in the crystal structure allows us to exclude restriction of motion as the reason for the absence of Sd photoisomerization in the hairpins. Conformational differences in the stem portion of the two hairpin molecules go along with different Mg(2+) binding modes. Most remarkable among them is the sequence-specific coordination of a metal ion in the narrow A-tract minor groove. The crystal structure provides unequivocal evidence that a fully hydrated Mg(2+) ion can penetrate the narrow A-tract minor groove, causing the groove to further contract. Overall, the structural data provide a better understanding of the origins of hairpin stability and their photochemical behavior in solution.     

The selective recognition of mismatched d(GCGAGC)_2 by the cobalt(III) complex

Base mismatches arise naturally in the life cycleof a cell as a result of either polymerase error or DNAdamage. Under most circumstances the cell correctsthese mispairings using a complex repair system toprevent mutations in the genetic code. Experimental…     

DNA小沟结合药物DB818的分子动力学模拟和结合自由能分析

采用分子动力学模拟了DNA小沟结合芳香二脒药物DB818形成的复合物. 通过5 ns的模拟研究表明: DB818药物分子可紧密结合在DNA的AATTC小沟区域, 和双螺旋d[CGCGAATTCGCG]2形成稳定的复合物. 由于噻吩硫原子的弱电负性, 使DB818能够以更大的伸展程度与DNA的小沟结合, 形成更强的结合力. DB818苯并咪唑的氮原子能够与DNA 7位和19位T碱基上的氧原子形成两个稳定的氢键, 同时, DB818末端氨基氮原子分别与DNA 的20位T碱基的氧原子和9位C碱基的氧原子形成两个氢键. 另外, 运用MM_PBSA方法计算了DB293-DNA和DB818-DNA复合物的结合自由能, 计算结合能与实验值能较好的吻合, 通过比较其结合自由能, 从热力学能量角度说明了DB818有较大的熵值与较小的焓值贡献, 从而与DNA小沟结合的结合力比DB293强. 本文在分子水平上提供了DB818直接与双螺旋DNA相互作用的结构及复合物的动态变化情况, 为设计出更高生物活性的DNA小沟结合剂提供一定的理论依据.     

Long range 1,4 and 1,6-interstrand cross-links formed by a trinuclear platinum complex. Minor groove preassociation affects kinetics and mechanism of cross-link formation as well as adduct structure

Reported here is a comparison of the kinetics of the stepwise formation of 1,4- and 1,6-GG interstrand cross-links by the trinuclear platinum anticancer compound (15)N-[[trans-PtCl(NH(3))(2)](2)[mu-trans-Pt(NH(3))(2)(H(2)N(CH(2))(6)NH(2))(2)]](4+), (1,0,1/t,t,t (1) or BBR3464). The reactions of (15)N-1 with the self-complementary 12-mer duplexes 5'-[d(ATATGTACATAT)(2)] (I) and 5'-[d(TATGTATACATA)(2)] (II) have been studied at 298 K, pH 5.3 by [(1)H,(15)N] HSQC 2D NMR spectroscopy. The kinetic profiles for the two reactions are similar. For both sequences initial electrostatic interactions with the DNA are observed for 1 and the monoaqua monochloro species (2) and changes in the chemical shifts of certain DNA (1)H resonances are consistent with binding of the central charged [PtN(4)] linker unit in the minor groove. The pseudo first-order rate constants for the aquation of 1 to 2 in the presence of duplex I (3.94 +/- 0.03 x 10(-5) s(-1)), or II(4.17 +/- 0.03 x 10(-5) s(-1)) are ca. 40% of the value obtained for aquation of 1 under similar conditions in the absence of DNA. Monofunctional binding to the guanine N7 of the duplex occurs with rate constants of 0.25 +/- 0.02 M(-1) s(-1) (I) and 0.34 +/- 0.02 M(-1) s(-1) (II), respectively. Closure to form the 1,4- or 1,6-interstrand cross-links (5) was treated as direct from 3 with similar rate constants of 4.21 +/- 0.06 x 10(-5) s(-1) (I) and 4.32 +/- 0.04 x 10(-5) s(-1) (II), respectively. Whereas there is only one predominant conformer of the 1,6 cross-link, evidence from both the (1)H and [(1)H,(15)N] NMR spectra show formation of two distinct conformers of the 1,4 cross-link, which are not interconvertible. Closure to give the major conformer occurs 2.5-fold faster than for the minor conformer. The differences are attributed to the initial preassociation of the central linker of 1 in the minor groove and subsequently during formation of both the monofunctional and bifunctional adducts. For duplex I, molecular models indicate two distinct pathways for the terminal [PtN(3)Cl] groups to approach and bind the guanine N7 in the major groove with the central linker anchored in the minor groove. To achieve platination of the guanine residues in duplex II the central linker remains in the minor groove but 1 must diffuse off the DNA for covalent binding to occur. Clear evidence for movement of the linker group is seen at the monofunctional binding step from changes of chemical shifts of certain CH(2) linker protons as well as the Pt-NH(3) and Pt-NH(2) groups. Consideration of the (1)H and (15)N shifts of peaks in the Pt-NH(2) region show that for both the 1,4 and 1,6 interstrand cross-links there is a gradual and irreversible transformation from an initially formed conformer(s) to product conformer(s) in which the amine protons of the two bound [PtN(3)] groups exist in a number of different environments. The behavior is similar to that observed for the 1,4-interstrand cross-link of the dinuclear 1,1/t,t compound. The potential significance of preassociation in determining kinetics of formation and structure of the adducts is discussed. The conformational flexibility of the cross-links is discussed in relation to their biological processing, especially protein recognition and repair, which are critical determinants of the cytotoxicity of these unique DNA-binding agents.     

Does Hydrogen Bonding Matter in Crystal Engineering? Crystal Structures of Salts of Isomeric Ions

The preparation and structure determinations of the crystalline salts [3,3'-H(2)bipy][PtCl(4)] (2), [2,2'-H(2)bipy][PtCl(4)] (3) and [1,4'-Hbipy][PtCl(4)] (4) and [3,3'-H(2)bipy][SbCl(5)] (6) and [1,4'-Hbipy][SbCl(5)] (8) are reported. In addition a redetermination of the structure of the metastable salt [4,4'-H(2)bipy][SbCl(5)] (5 b) in the corrected space group Pbcm is described. These structures are compared to those of the known salt [4,4'-H(2)bipy][PtCl(4)] (1), the stable triclinic form of [4,4'-H(2)bipy][SbCl(5)] (5 a) and [2,2'-H(2)bipy][SbCl(5)] (7). In the case of the salts of the rigid [PtCl(4)](2-) ion, structures 2, 3 and 4 are essentially isostructural despite the differing hydrogen-bonding capability of the cations. Similarly, among the salts of [SbCl(5)](2-) ions, structures 7 and 8 are essentially isostructural. Structure 6 differs from these in having a differing pattern of aggregation of the [SbCl(5)](2-) ions to form polymeric rather than tetrameric units. It is evident that local hydrogen-bonding interactions, although significant, are not the only or even the decisive influence on the crystal structures formed by these salts. These observations are not in good accord with the heuristic "sticky tecton" or supramolecular synthon models for synthetic crystallography or crystal engineering.     

△,Λ-[Co(phen)2tpphz]^3+与B - DNA相互作用的分子 模拟

针对国际上对金属配合物同DNA间作用机量的争议,采用分子模拟手段在MM2力场下,搭建并优化了手性金属配合物△,Λ-[Co(phen)2tpphz]^3+与B-DNA[d(GTCGATCGAC)2]的模型,继而对其相互作用进行了模拟,得出的结论是：对所采用的B-DNA片断,该金属配合物有明显的立体选择性△型配合物从小沟插入占明显优势,而且,总体来看,从AT区插入更易进行。     

Influence of the dynamic positions of cations on the structure of the DNA minor groove: sequence-dependent effects

Different models for minor groove structures predict that the conformation is essentially fixed by sequence and has an influence on local ion distribution or alternatively that temporal positions of ions around the minor groove can affect the structure if they neutralize cross-strand phosphate charges. Our previous studies show that the minor groove in an AATT dodecamer responds to local sodium ion positions and is narrow when ions neutralize cross-strand phosphate-phosphate charges [J. Am. Chem. Soc. 2000, 122, 10513-10520]. Previous results from a number of laboratories have shown that G-tracts often have a wider minor groove than A-tracts, but they do not indicate whether this is due to reduced flexibility or differences in ion interactions. We have undertaken a molecular dynamics study of a d(TATAGGCCTATA) duplex to answer this question. The results show that the G-tract has the same amplitude of minor groove fluctuations as the A-tract sequence but that it has fewer ion interactions that neutralize cross-strand phosphate charges. These results demonstrate that differences in time-average groove width between A- and G-tracts are due to differences in ion interactions at the minor groove. When ions neutralize the cross-strand phosphates, the minor groove is narrow. When there are no neutralizing ion interactions, the minor groove is wide. The population of structures with no ion interactions is larger with the GGCC than with the AATT duplex, and GGCC has a wider time-average minor groove in agreement with experiment.     

Synthesis, DNA binding, photo-induced DNA cleavage and cytotoxicity studies of europium(III) complexes

Two Eu(III) complexes, [Eu(acac)(3)(dpq)] (1) and [Eu(acac)(3)(dppz)] CH(3)OH (2) {viz. acetylacetonate (acac), dipyrido[3,2-d:20,30-f]quinoxaline (dpq), dipyrido[3,2-a:20,30-c] phenazine (dppz)}, have been synthesized and their DNA binding, photo-induced DNA cleavage activity and cell cytotoxicity are studied. The complexes display significant binding propensity to the calf thymus DNA in the order: 2(dppz) >1(dpq). Cleavage experiments using pBR322 supercoiled DNA suggest major groove binding for 2 and minor groove binding for 1. The mechanistic aspects on natural light (natural light in room during the day) and UV-A (365 nm) irradiation are via a mechanistic pathway involving formation of singlet oxygen and hydroxyl radical as the reactive species. The photo-induced DNA cleavage activity of 2 is also stronger than 1. The cytotoxicity of 1 and 2 against HeLa (cervical) cancer cells show that the IC(50) value of 19.11 ± 3.56 μM and 17.95 ± 5.47 μM, respectively.     

DNA小沟结合二脒:水分子的识别作用

采用分子动力学模拟了DB921-DNA复合物, 通过7 ns的模拟研究表明: DB921一端的氨基氮原子与一个水分子形成氢键, 同时, 水分子又与DNA的5位A碱基的氮原子形成一个氢键. 水分子在DB921与DNA小沟结合中起了桥连的作用, 使得直线型的芳香二脒化合物DB921通过水桥与DNA小沟结合, 水分子诱导DB921分子与DNA的小沟域构型相适应, 与DNA小沟域的AATTC碱基有较强的结合作用. 在分子水平上提供了DB921与双螺旋DNA相互作用的结构及复合物的动态变化情况, 指出水分子在DNA小沟结合二脒化合物中的识别作用, 为设计出更高生物活性的DNA小沟结合剂提供一定的理论依据.     

The selective recognition of mismatched d(GCGAGC)2 by the cobalt(III) complex

We studied the binding of [Co(phen)₂(HPIP)]CI₃ to mismatched d(GCGAGC)₂ containing two sheared G:A mispairs by NMR. The result shows that the complex was intercalated into G:A region from the minor groove and extended to the major groove, and could selectively recognize the mispairs.³¹P NMR indicates that the complex binding induced the change of the phosphate backbone in the mismatched base pairs region.     

Oxozinc carboxylate complexes: a new synthetic approach and the carboxylate ligand effect on the noncovalent-interactions-driven self-assembly

An atom-efficient and mild synthesis of a series of oxozinc carboxylates [Zn(4)(μ(4)-O)(O(2)CR)(6)] [where R = Ph (2a), p-PhC(6)H(4) (2b), p-MeC(6)H(4) (2c), and p-MeSC(6)H(4) (2d)] from well-defined alkylzinc precursors and H(2)O is described. The molecular and crystal structures of the resulting complexes have been determined by single-crystal X-ray diffraction. A closer examination of their crystal structure provides a direct picture of the effect of the nature of substituents on the molecular self-assembly of the octahedral oxozinc through noncovalent interactions. It was revealed that these discrete oxozinc clusters can form diverse types of noncovalent assemblies ranging from structures representing zeolitic topologies in the case of 2a to soft porous materials with gated voids or open channels for the remaining molecular clusters.     

诺氟沙星-DNA复合物的分子动力学模拟

采用分子模建的方法构建了诺氟沙星-DNA复合物的初始结构, 通过2 ns的分子动力学(MD)模拟研究表明: 诺氟沙星能够和双螺旋d[ATATCGATAT]₂形成稳定的复合物, 药物分子可紧密结合在DNA的小沟区域, 并且能够与DNA的鸟嘌呤碱基形成两个稳定的氢键. 在分子水平上提供了诺氟沙星直接与双螺旋DNA相互作用的结构及复合物的动态变化情况.     

Atomic Resolution Insight into Sac7d Protein Binding to DNA and Associated Global Changes by Molecular Dynamics Simulations

Sac7d is a small, thermostable protein that induces large helical deformations in DNA upon association. Starting from multiple initial placements of the unbound Sac7d structure relative to a B‐DNA oligonucleotide, molecular dynamics (MD) simulations were employed to directly follow several successful binding events at atomic resolution that resulted in structures in close agreement with the native complex geometry. The final native complex formed rapidly within tenths of nanoseconds and included simultaneous large‐scale kinking, groove opening, twisting, and intercalation in the target DNA. The simulations indicate that the complex formation process involves initial non‐native contacts that helped in reaching the final bound state, with residues intercalated at the center of the kinked DNA. It was also possible to identify several long‐lived trapped intermediate states of the binding process and to follow sliding processes of Sac7d along the DNA minor groove.     

Hydrothermal single-crystal growth in the systems Ag/Hg/X/O (X = VV, AsV): crystal structures of (Ag3Hg)VO4, (Ag2Hg2)3(VO4)4, and (Ag2Hg2)2(HgO2)(AsO4)2 with the unusual tetrahedral cluster cations (Ag3Hg)3+ and (Ag2Hg2)4+ and crystal structure of AgHgVO4

Single crystals of (Ag3Hg)VO4 (I), (Ag2Hg2)3(VO4)4 (II), AgHgVO4 (III), and (Ag2Hg2)2(HgO2)(AsO4)2 (IV) were grown under hydrothermal conditions (250 degrees C, 5 d) from starting mixtures of elementary mercury, silver nitrate, ammonium vanadate, and disodium hydrogenarsenate, respectively. All crystal structures were determined from X-ray diffraction data, and their chemical compositions were confirmed by electron microprobe analysis. I crystallizes in the tillmannsite structure, whereas II-IV adopt new structure types: (I) I4, Z = 2, a = 7.7095(2) A, c = 4.6714(2) A, 730 structure factors, 24 parameters, R[F2 > 2sigma(F2)] = 0.0365; (II) I42d, Z = 4, a = 12.6295(13) A, c = 12.566(3) A, 1524 structure factors, 55 parameters, R[F2 > 2sigma(F2)] = 0.0508; (III) C2, Z = 4, a = 9.9407(18) A, b = 5.5730(8) A, c = 7.1210(19) A, beta = 94.561(10) degrees , 1129 structure factors, 48 parameters, R[F2 > 2sigma(F2)] = 0.0358; (IV) P31c, Z = 2, a = 6.0261(9) A, c = 21.577(4) A, 1362 structure factors, 52 parameters, R[F2 > 2sigma(F2)] = 0.0477. The most striking structural features of I, II, and IV are the formation of tetrahedral cluster cations (Ag3Hg)3+ and (Ag2Hg2)4+, respectively, built of statistically distributed Ag and Hg atoms with a metal-metal distance of about 2.72 A. The electronic structure of these clusters can formally be considered as two-electron-four-center bonding. The crystal structure of III differs from the protrusive structure types insofar as silver and mercury are located on distinct crystallographic sites without a notable metal-metal interaction >3.55 A. All crystal structures are completed by tetrahedral oxo anions XO4(3-) (X = VV, AsV) and for IV additionally by a mercurate group, HgO2(2-).     

New mononuclear copper(II) complexes from β-diketone and β-keto ester N-donor heterocyclic ligands: structure,bioactivity, and molecular simulation studies

Four new mononuclear copper(II) complexes with methyl acetoacetate and benzoylacetone in the presence of 1,10-phenanthroline and 2,2′-bipyridine were synthesized and characterized by elemental analyses, FT-IR, and UV–Vis spectroscopy. The molecular structures of complexes [Cu(MAA)(bpy)(ClO₄)] (1a), [Cu(bzac)(bpy)]ClO₄ (2a), [Cu(MAA)(phen)(ClO₄)] (1b) and [Cu(bzac)(phen)(ClO₄)] (2b) were determined by single crystal X-ray diffraction technique. 1a, 1b, and 2b are five coordinate with a distorted square pyramidal geometry and the structure of 2a consists of isolated [Cu(bzac)(bpy)]⁺ cations and perchlorate counter anions. The electrochemical studies of copper complexes in acetonitrile solution showed that Cu^II/Cu^I reduction processes are electrochemically irreversible. Cytotoxic activity of complexes was screened, including an MTT assay against gastric cancer cell line (MKN-45). The four Cu(II) complexes exhibited lethal effects against MKN-45 cell lines and the half maximal inhibitory concentration (IC₅₀) values obtained were much lower in comparison with 5-fluorouracil. In addition, MTT and migration studies revealed that benzoylacetone complexes are more active than complexes of methyl acetoacetate against the MKN-45 cancer cell lines. Docking simulations of Cu(II) complexes on DNA revealed that the most stable adducts with DNA bind in the minor groove. All complexes display a binding specificity to the A/T rich regions.