Application of capillary electrophoresis-mass spectrometry for the investigation of the binding behavior of oxaliplatin to 5'-GMP in the presence of the sulfur-containing amino acid L-methionine

Capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) has been used for investigating the influence of the sulfur containing amino acid L-methionine (L-Met) on the binding behavior of oxaliplatin (trans-R,R-diaminocyclohexane-(oxalato)platinum(II)) to 5'-GMP. L-Methionine competes with 5'-GMP for the platinum binding site and forms as well as 5'-GMP adducts with oxaliplatin. The formation of the prognosed complexes [Pt(DACH)(L-Met-S,N)]+ and [Pt(DACH)(5'-GMP)2]2- (DACH = 1,2-diaminocyclohexane) could be proved directly by using CE-ESI-MS. Furthermore, we could now bring forward proofs, that the coordination of 5'-GMP with oxaliplatin is inhibited by L-methionine and could show, that the 5'-GMP ligands of the [Pt(DACH) (5'-GMP)2]2- complex can be replaced slowly by L-methionine whereas methionine can not be replaced by GMP.     

fac-[Re(CO)3(H2O)3]+ nucleoside monophosphate adducts investigated in aqueous solution by multinuclear NMR spectroscopy

The fac-[Re(CO)3(H2O)3]+ cation, the putative DNA-binding species accounting for the biological activity of related Re(I) complexes, binds reversibly to N7 of 6-oxopurine nucleotide monophosphates (NMPs), in contrast to Pt(II) anticancer drugs. A relatively high amount of NMP is needed to convert all of the fac-[Re(CO)3(H2O)3]+ to adducts. The Re/nucleotide 1:1 adduct forms more rapidly and builds up to a higher concentration for guanosine 5'-monophosphate (5'-GMP) and inosine 5'-monophosphate (5'-IMP) than for the respective 3'-monophosphates (3'-GMP and 3'-IMP). These results are attributable to the 5'-positioning of the 5'-NMP phosphate group that allows it to approach the metal inner sphere for more favorable cation electrostatic and aqua ligand H-bonding interactions, both in the initial productive ion pair encounter complexes and in the N7-bound 1:1 adducts. A higher reactivity of 5'-GMP over 3'-GMP is known for cisplatin. In contrast, more Re/nucleotide 1:2 adduct was formed by 3'-GMP (and 3'-IMP) than by 5'-GMP (and 5'-IMP). Because the 3'-phosphate group cannot closely approach the metal inner coordination sphere, the greater stability for the 3'-GMP 1:2 adduct reflects the more favorable G N1H-phosphate interligand GMP-GMP interactions for 3'-GMP vs 5'-GMP (G=guanine base derivative). This type of interaction is known for platinum adducts. In 1:2 adducts the bound nucleotides are inequivalent, prompting us to perform mixed 5'-GMP/3'-GMP experiments, leading to the observation of major (M) and minor (m) mixed Re/5'-GMP/3'-GMP 1:1:1 adducts. The order of abundance at equilibrium in a typical experiment was M>bis 3'-GMP>m>or=bis 5'-GMP. This stability order was rationalized by invoking the phosphate interactions described above. When methionine and 5'-GMP were allowed to compete for fac-[Re(CO)3(H2O)3]+, the Re/5'-GMP 1:1 adduct was the kinetic product and the S-bound Re/methionine adduct was the thermodynamic product, a result opposite to that typically found for cisplatin.     

Disodium guanosine 5'-monophosphate self-associates into nanoscale cylinders at pH 8: a combined diffusion NMR spectroscopy and dynamic light scattering study

We report a combined NMR and dynamic light scattering (DLS) study on the size of supramolecular structures formed by disodium guanosine 5'-monophosphate, Na(2)(5'-GMP), at pH 8. In general, two distinct types of aggregate species are present in an aqueous solution of Na(2)(5'-GMP). One type consists of stacking 5'-GMP monomers, and the other contains stacking G-quartets. Both types of aggregates can be modeled as rodlike cylinders. The cylinder diameter is 10 and 26 A for monomer aggregates and quartet aggregates, respectively. For Na(2)(5'-GMP) concentrations between 18 and 34 wt %, the cylinders formed by stacking G-quartets have an average length between 8 and 30 nm, corresponding to a stack of approximately 24-87 G-quartets. These nanoscale aggregates are significantly larger than what had previously been believed for Na(2)(5'-GMP) self-association at pH 8. The length of both types of 5'-GMP aggregates was found to increase with Na(2)(5'-GMP) concentration but was insensitive to the added NaCl in solution. While the aggregate size for monomer aggregates increases with a decrease in temperature, the size of G-quartet aggregates is essentially independent of temperature. We found that the size of G-quartet aggregates is slightly larger in D(2)O than in H(2)O, whereas the size of monomer aggregates remains the same in D(2)O and in H(2)O. We observed a linear relationship between the axial ratio of the 5'-GMP cylinders and the Na(2)(5'-GMP) concentration for both types of 5'-GMP aggregates, which suggests a common stacking mechanism for monomers and G-quartets.     

稀土元素对腺嘌呤及鸟嘌呤单核苷酸的水解断裂作用

本文研究稀土元素对5'-腺嘌呤核苷酸(5'-AMP)和5'-鸟嘌呤核苷酸(5'-GMP)的水解断裂作用。空气中CeCl~3在pH 9,37℃能有效地水解断裂5'-AMP及5'-GMP,而其它三价稀土对5'-AMP和5'-GMP的水解断裂作用很小, 铈对5'-AMP的水解断裂速度大于5'-GMP。紫外吸收光谱实验结果表明反应体系中Ce(Ⅲ)部分被氧化成Ce(Ⅳ), Ce(Ⅳ)的氢氧簇合物是使5'-AMP和5'-GMP水解的活性组分。     

The self-assembly and lyotropic mesomorphism of riboguanylic acids (GMP)

The three isomeric guanylic acids (5'-GMP, 3'-GMP and 2'-GMP) and the 3':5'-cyclic derivative (cGMP) form, in water solution, left-handed columnar aggregates which, at higher concentration, pack to give left-handed cholesteric mesophases. The self-assembly process and liquid crystal formation are discussed in relation to the behaviour of the 2'-deoxy analogues.     

Cu(II)-氨基酸-核苷酸三元配合物的合成和表征

合成和表征Na~2[Cu(L-Ala)~2(5'-GMP)].2H~2O、Na~2[Cu(L-Ala)~2(5'-IMP)].6H~2O、Na~2[Cu(L-His)(5'-GMP)Cl~2^2.2H~2O和Na~2[Cu(L-His)(5'-IMP)Cl~2].H~2O四个新的三元配合物, 其中两个L-Ala分子通过羧基O和α-氨基N与Cu(II)成反式配位, 一个L-His分子通过羧基O和咪唑环上的N与Cu(II)配位; 一个5'-GMP或5'-IMP分子嘌呤环上的N(7)与Cu(II)配位; 5'-GMP的磷酸根上可能存在强氢键, 而5'-IMP的磷酸根上不存在强氢键; 在含L-Ala三元配合物中, 5'-GMP的C(6)=0可能参与配位或形成强氢键, 而5'-IMP的C(6)=0不参与配位或形成配位或形成强氢键; 在含L-His三元配合物中, 5'-IMP的C(6)=0的表现则相反。     

Neglected bidentate sp2 N-donor carrier ligands with triazine nitrogen lone pairs: platinum complexes retromodeling cisplatin guanine nucleobase adducts

Rapid rotation of guanine base derivatives about Pt-N7 bonds results in fluxional behavior of models of the key DNA intrastrand G-G cross-link leading to anticancer activity of Pt(II) drugs (G = deoxyguanosine). This behavior impedes the characterization of LPtG2 models (L = one bidentate or two cis-unidentate carrier ligands; G = guanine derivative not linked by a phosphodiester group). We have examined the formation of LPtG2 adducts with G = 5'- and 3'-GMP and L = sp(2) N-donor bidentate carrier ligands [5,5'-dimethyl-2,2'-bipyridine (5,5'-Me2bipy), 3-(4'-methylpyridin-2'-yl)-5,6-dimethyl-1,2,4-triazine) (MepyMe2t), and bis-3,3'-(5,6-dialkyl-1,2,4-triazine) (R4dt)]. NMR spectroscopy provided conclusive evidence that these LPt(5'-GMP)2 complexes exist as interconverting mixtures of head-to-tail (HT) and head-to-head (HH) conformers. For a given G, the rates of G base rotation about the Pt-N7 bonds of LPtG2 models decrease in the order Me4dt > Et4dt > MepyMe2t > 5,5'-Me2bipy. This order reveals that the pyridyl ring C6 atom + H atom grouping is large enough to impede the rotation, but the equivalently placed triazine ring N atom + N lone pair grouping is sterically less impeding. For the first time, the two possible HH conformers (HHa and HHb) in the case of an unsymmetrical L have been identified in our study of (MepyMe2t)Pt(5'-GMP)2. Although O6-O6 clashes involving the two cis G bases favor the HT over the HH arrangement for most LPtG2-type complexes, the HH conformer of (R4dt)Pt(5'-GMP)2 adducts has a high abundance (approximately 50%). We attribute this high abundance to a reduction in O6-O6 steric clashes permitted by the overall low steric effects of R4dt ligands. Under the reaction conditions used, 3'-GMP forms a higher abundance of the LPt(GMP)2 adduct than does 5'-GMP, a result attributable to more favorable second-sphere communication in the LPt(3'-GMP)2 adduct than in the LPt(5'-GMP)2 adduct.     

Circular dichroism and UV-Vis absorption spectroscopic monitoring of production of chiral silver nanoparticles templated by guanosine 5'-monophosphate

Herein we report the chemical reduction of silver ions incorporated into chiral supramolecular nanostructures by NaBH(4) in buffered (basic) and unbuffered conditions. In situ self-assembly of guanosine 5'-monophosphate (5'-GMP) templated by Ag(I) and generation of silver nanoparticles (NPs) were continuously monitored by CD and UV-Vis spectroscopy measurements. 5'-GMP has been identified as an efficient chiral organic ligand to complex silver ions into a hierarchical helical nanostructure and is a useful capping agent for stabilizing silver NPs with a size diameter lower than 20 nm. The observation of opposite signed bands in the CD spectra of Ag(I)/5'-GMP complexes at different pH has suggested the existence of opposite-handed supramolecular helical structures depending on pH. Both helical supramolecular structures induce chirality in the silver NPs during their growth of the same handedness as shown by the CD signals in the plasmon resonance band.     

Pyridine-carboxylate complexes of platinum. Effect of N,O-chelate formation on model bifunctional DNA-DNA and DNA-protein interactions

This paper reports on the chemistry of platinum complexes containing bidentate pyridine-carboxylate (pyAc = pyridin-2-yl-acetate and picEt = pyridine-2-ethylcarboxylate, ethylpicolinate) (N,O) ligands. The pyridine-2-acetate and ethylpicolinate ligands form six- and five-membered chelates, respectively, upon formation of the Pt-carboxylate bond. In all reactions with picEt with various platinum complex starting materials, spontaneous de-esterification of the pendant carboxylate ester occurs to give directly the chelates K[PtCl(2)(pic-N,O)]-trans-[Pt(pic-N,O)(2)] and SP-4,2-[PtCl(pic-N,O)(NH(3))] without any evidence of intermediates. The de-esterification is solvent dependent, and molecular modeling was used to explain this reaction. The reactions of the geometric isomers of [PtCl(pyAc-N,O)(NH(3))] with 5'-guanosine monophosphate, 5'-GMP, and N-acetyl-l-methionine, AcMet, were investigated by NMR spectroscopy. The objective was to ascertain by model chemistry the feasibility of formation of ternary DNA-Pt-protein adducts in biology. Model nucleotide and peptide compounds were formed in situ by chloride displacement giving [PtL(pyAc-N,O)(NH(3))](+) (L = 5'-GMP or AcMet). Competitive reactions were then examined by addition of the complementary ligand L. Sulfur displacement of coordinated 5'-GMP was slow. For SP-4,3-[Pt(AcMet)(NH(3))(PyAc-N,O)](+), a rapid displacement of the sulfur ligand by 5'-GMP was observed, giving SP-4,2-[Pt(5'-GMP-N7)(pyAc-N,O)(NH(3))](+).     

Reaction monitoring of platinum(II) complex--5'-guanosine monophosphate adduct formation by ion exchange liquid chromatography/electrospray ionization mass spectrometry

Cisplatin and four structurally related platinum(II) complexes were incubated with guanosine 5'-monophosphate (5'-GMP) in water at 37 degrees C. The adduct formation reactions were monitored with cation- and anion-exchange liquid chromatography/electrospray ionization mass spectrometry. In addition to mono- and bis-adducts of guanosine 5'-monophosphate with the platinum(II) complexes, other molecular species, presumably with a binuclear structure (two platinum(II) centres), were detected in the reaction mixtures, which have not been reported previously, indicating an unexpected complexity of adduct formation. Anion-exchange chromatography revealed the presence of isomers of two complexes which presumably result from the restricted rotation at the platinum-- N-7 (5'-GMP) bonds. All reaction products were characterized in both the positive and negative ion modes. Furthermore, preliminary kinetics and half-times of complex formation were investigated for cisplatin and two other platinum(II) complexes, monitoring the relative concentrations of free 5'-GMP and of mono- and bis-GMP adducts as a function of time (250 h) using an internal standard protocol with thymidine 5'-monophosphate.     

Equilibrium studies of the reactions of palladium(II) bis(imidazolin-2-imine) complexes with biologically relevant nucleophiles. The crystal structures of [(TLtBu)PdCl]ClO4 and [(BLiPr)PdCl2

The kinetics and the mechanism of the substitution reactions of the complex [(TL(tBu))PdCl](+), where TL(tBu) is 2,6-bis[(1,3-di-tert-butylimidazolin-2-imino)methyl]pyridine, with nucleophiles (guanosine-5'-monophosphate (5'-GMP), l-Methionine (l-Met) and l-Histidine (l-His)) were studied using variable-temperature stopped-flow techniques in aqueous 0.1 M NaClO(4) with 10 mM NaCl at 298 K. The order of reactivity is: l-Met > 5'-GMP > l-His. The formation equilibria of [(BL(iPr))Pd(H(2)O)(2)](2+), where BL(iPr) is 1,2-bis(1,3diisopropyl-4,5-dimethylimidazolin-2-imino)ethane, and [(TL(tBu))Pd(H(2)O)](2+) with some biologically relevant ligands (l-Met, 5'-GMP and l-His) were also studied. The stoichiometry and stability constants of the newly formed complexes are reported, and the concentration distribution of the various complex species has been evaluated as a function of pH. Comparing the values of logβ(1,1,0) for 5'-GMP, l-His and l-Met complexes, the most stable complex is with 5'-GMP followed by l-His and l-Met for both complexes, [(BL(iPr))Pd(H(2)O)(2)](2+) and [(TL(tBu))Pd(H(2)O)](2+). The crystal structures of [(TL(tBu))PdCl]ClO(4) and [(BL(iPr))PdCl(2)] were determined by X-ray diffraction. The coordination geometries around the palladium atoms are distorted square-planar, with the Pd-N1 distance to the central nitrogen atom of the TL(tBu) ligand, 1.944(2) ?, being shorter than those to the other two nitrogen atoms of TL(tBu), viz. 2.034(3) and 2.038(2) ?. The BL(iPr) complex displays similar Pd-N distances of 2.031(2) and 2.047(2) ?.     

PHOTO-CIDNP IN GUANINE NUCLEIC ACID DERIVATIVES. A MECHANISTIC STUDY

Abstract— A mechanistic study of the photo-CIDNP effect of guanosine derivatives is presented. The pH dependence of the CIDNP effect of 5'-GMP shows a sign reversal at pH 3.3. Using methylated guanosine derivatives evidence has been obtained that the protonation state of the N7 atom influences the radical pair generation. The mechanism involves a guanine radical dication (protonated radical cation) at low pH and a radical cation at high pH. The CIDNP behaviour of 5'-GMP is compared with that of 5'-AMP, that was previously studied.     

Equilibrium, kinetic and HPLC study of the reactions between platinum(II) complexes and DNA constituents in the presence and absence of glutathione

The complex formation equilibria of [Pt(SMC)(H(2)O)(2)](+) and [Pt(terpy)H(2)O](2+), where SMC =S-methyl-L-cysteine and terpy = 2,2':6',2"-terpyridine, with some biologically relevant ligands such as inosine (INO), inosine-5'-monophosphate (5'-IMP), guanosine-5'-monophosphate (5'-GMP) and glutathione (GSH) were studied. The stoichiometry and stability constants of the complexes formed are reported, and the concentration distribution of the various complex species have been evaluated as a function of pH. Also the kinetics and mechanism of the complex formation reactions were studied as a function of nucleophile concentration and temperature. For the complex [Pt(SMC)(H(2)O)(2)](+), two consecutive reaction steps, which both depend on the nucleophile concentration, were observed under all conditions. The negative entropies of activation support an associative complex formation mechanism. Reaction of guanosine-5'-monophosphate (5'-GMP) with Pt(II) complexes was carried out in the presence and absence of glutathione (GSH) at neutral pH. The rate constants clearly showed a kinetic preference toward GSH at neutral pH. The reactions were also monitored by HPLC. However, only a small amount of coordinated 5'-GMP was detected in the HPLC trace. The products were isolated and characterized by MALDI-TOF mass spectrometry.     

Selective binding of monovalent cations to the stacking G-quartet structure formed by guanosine 5'-monophosphate: a solid-state NMR study

We report a solid-state multinuclear ((23)Na, (15)N, (13)C, and (31)P) NMR study on the relative affinity of monovalent cations for a stacking G-quartet structure formed by guanosine 5'-monophosphate (5'-GMP) self-association at pH 8. Two major types of cations are bound to the 5'-GMP structure: one at the surface and the other within the channel cavity between two G-quartets. The channel cation is coordinated to eight carbonyl oxygen atoms from the guanine bases, whereas the surface cation is close to the phosphate group and likely to be only partially hydrated. On the basis of solid-state (23)Na NMR results from a series of ion titration experiments, we have obtained quantitative thermodynamic parameters concerning the relative cation binding affinity for each of the two major binding sites. For the channel cavity site, the values of the free energy difference (Delta G degrees at 25 degrees C) for ion competition between M(+) and Na(+) ions are K(+) (-1.9 kcal mol(-1)), NH(4)(+) (-1.8 kcal mol(-1)), Rb(+) (-0.3 kcal mol(-1)), and Cs(+) (1.8 kcal mol(-1)). For the surface site, the values Delta G degrees are K(+) (2.5 kcal mol(-1)), NH(4)(+) (-1.3 kcal mol(-1)), Rb(+) (1.1 kcal mol(-1)), and Cs(+) (0.9 kcal mol(-1)). Solid-state NMR data suggest that the affinity of monovalent cations for the 5'-GMP structure follows the order NH(4)(+) > Na(+) > Cs(+) > Rb(+) > K(+) at the surface site and K(+) > NH(4)(+) > Rb(+) > Na(+) > Cs(+) > Li(+) at the channel cavity site. We have found that the cation-induced stability of a 5'-GMP structure is determined only by the affinity of monovalent cations for the channel site and that the binding of monovalent cations to phosphate groups plays no role in 5'-GMP self-ordered structure. We have demonstrated that solid-state (23)Na and (15)N NMR can be used simultaneously to provide mutually complementary information about competitive binding between Na(+) and NH(4)(+) ions.     

HPIC-UV-ICP-SFMS study of the interaction of cisplatin with guanosine monophosphate

Interaction of cis-[Pt(NH3)2Cl2] (cisplatin) with 5'-guanosine monophosphate (5'-GMP) has been investigated for the first time by on-line coupling of high performance ion chromatography (HPIC) to inductively coupled plasma sector field mass spectrometry (ICP-SFMS). The time-dependent reaction course of the cisplatin-5'-GMP system was followed after incubation under simulated physiological conditions by monitoring the decrease in the concentration of 5'-GMP and the increase in the concentration of formed adducts, on the basis of speciation analysis. Because of the two-step mechanism an intermediate mono adduct was observed together with the major product, the bis adduct cis-[Pt(NH3)2(GMP)2]2-. The data obtained correlated well with those from earlier studies employing orthogonal techniques such as capillary electrophoresis (CE). Furthermore, HPIC-ICP-SFMS provided unambiguous stoichiometric information about the major GMP-adduct. For this purpose the platinum-to-phosphorus ratio was determined by simultaneously measuring 31P and 195Pt. To separate significant interferences from 15N16O+, 14N16O1H+, 12C18O1H+, and 13C17O1H+ on 31P, high-mass resolution (m/deltam = 4,500) proved to be mandatory. The P/Pt signal ratio of 2/1 obtained corresponds to the molar ratio in the bis adduct cis-[Pt(NH3)2(GMP)2]2-.     

[Cu(dien)Cl]+与核苷酸作用的1H、31P NMR研究

本文用~1H-NMR和~(31)P-NMR谱研究了[Cu(dien)Cl]~+与5＇-AMP、5＇-GMP和5＇-CMP在pD=6.00条件下的共价键合作用.氢核磁共振谱研究表明[Cu(dien)]~(2+)与5＇-AMP可以在N-7和N-1位上键合,但N-7是最有利的键合位置.配离子与5＇-GMP、5＇-CMP、分别键合在N-7和N-3位置上.~(31)P核磁共振谱研究结果则表明[Cu(dien)]~(2+)还可以与单核苷酸上的磷酸酯根键合.并根据显著加宽质子峰及~(31)P峰的最低[Cu(dien)Cl]~+浓度,比较了[Cu(dien)]~(2+)对三种核苷酸的碱基与磷酸酯根的亲力.     

Synthesis, structures, and electrochemistry of gold(III) ethylenediamine complexes and interactions with guanosine 5'-monophosphate

[Au(en)Cl(2)]Cl.2H(2)O, where en = ethylenediamine (1,2-diaminoethane), has been synthesized, and its structure has been solved for the first time by the single-crystal X-ray diffraction method. The complex has square-planar geometry about Au(III), and the anionic Cl- is located in the apical position and at a distance of 3.3033(10) A compared to 2.2811(9) and 2.2836(11) A for the coordinated Cl-. [Au(en)Cl2]Cl.2H2O belongs to the space group Pbca with a = 11.5610(15) A, b = 12.6399(17) A, c = 13.2156(17) A, alpha = beta = gamma = 90 degrees , and Z = 8. Bond lengths of Au-N are 2.03 A. [Au(en)Cl2]Cl.2H2O is less thermally stable than [Au(en)2]Cl3 because of the replacement of two Cl ligands by a second en ligand in the latter. Cyclic voltammetry shows that the formal potential of Au(III)/Au(0) becomes more negative in the series [AuCl4]-, [Au(en)Cl2]+, and [Au(en)2]3+. 1H, 13C, and 31P NMR reveal that in an aqueous solution [Au(en)Cl2]+ bonds to guanosine 5'-monophosphate, 5'-GMP (1:1 mole ratio), via N7, although the stability is not very high. NMR data also indicate that N7-O6 or N7-phosphate 5'-GMP chelation, as found in some gold(III) nucleotide complexes, is not present. The gold(III) complex undergoes hydrolysis at pH >2.5-3.0 and, therefore, N1 coordination to 5'-GMP is not observed. No direct coordination between 5'-GMP and [Au(en)2]Cl3 is observed.     

The neglected Pt-N(sulfonamido) bond in Pt chemistry. New fluorophore-containing Pt(II) complexes useful for assessing Pt(II) interactions with biomolecules

Treatment of cis-Pt(Me2SO)2Cl2 with DNSH-tren afforded [Pt(DNSH-tren)Cl]Cl and with DNSH-dienH, under increasingly more basic conditions, led to Pt(DNSH-dienH)Cl(2), Pt(DNSH-dien)Cl, and Pt(DNS-dien). (DNSH = 5-(dimethylamino)naphthalene-1-sulfonyl, linked via a sulfonamide group to tris(2-aminoethyl)amine (DNSH-tren) and diethylenetriamine (DNSH-dienH); the H's in DNSH-dienH designate protons sometimes lost upon Pt binding, i.e., sulfonamide NH for the dienH moiety and H8 for the DNSH moiety). Respectively, the three neutral DNSH-dienH-derived complexes are difunctional, monofunctional, and nonfunctional and exhibit decreasing fluorescence in this order as the dansyl group distance to Pt decreases. 2D NMR data establish that Pt(DNS-dien) has a Pt-C8 bond and a Pt-N(sulfonamido) bond. Pt(DNSH-dien)Cl and [Pt(DNSH-tren)Cl]Cl bind to N7 of 6-oxopurines (e.g., 5'-GMP, 3'-IMP, and 9-ethylguanine) and sulfur of methionine (met). Competition and challenge reactions for Pt(II) with met and 5'-GMP typically reveal that met binding is favored kinetically but that 5'-GMP binding is favored thermodynamically. This common type of behavior was found for [Pt(DNSH-tren)Cl]Cl. In contrast, Pt(DNSH-dien)Cl had reduced kinetic selectivity for met. This unusual behavior undoubtedly arises as a consequence of the bound Pt-N(sulfonamido) group, which donates strongly to Pt (as indicated by relatively upfield dien NH signals) and which places the bulky DNSH moiety close to the monofunctional reaction site. The decrease in the relatively upfield shifts of the DNSH group signals indicates that this group stacks with the purine. This stacking could explain the unprecedented, relatively low reactivity of a Pt complex bearing a dien-type ligand toward met vs 5'-GMP.     

双核Pt(Ⅳ)配合物与Guanosine-5''''-Monophosphate和Glutathione反应的核磁共振光谱研究

合成了一个新型的双核Pt(Ⅳ)配合物{[cis-Pt(NH3)2Cl(OH)2]2(4,4'-methylenedianiline)}(NO3)2(化合物1)及相应的 15N标记化合物{[cis-Pt(15NH3)2Cl(OH)2]2(4,4'-methylenedianiline)}(NO3)2(化合物15N-1).利用1H NMR和ESMS进行了结构表征,化合物15N-1的2D[1H,15N]HSQC NMR发现,该化合物在水溶液中存在同分异构体.2D[1H,15N]HSQC NMR技术跟踪了化合物15N-1与Guanosine-5'-Monophosphate(5'-GMP)和Glutathione(GSH)的反应.结果显示,5'-GMP能在0.5 h内将化合物1还原,而GSH在6 h以后才能够部分的将化合物1还原.化合物1所表现出来的反应性能将有利于提高其治疗效果和降低毒副作用.     

Single atom modification leads to enhanced nucleotide self-assembly: the role of cation bridging

We report that the ability of disodium 5'-deoxy-5'-thioguanosine-5'-monophosphate, Na(2)(5'-GSMP), to self-associate into a helical G-quadruplex structure in aqueous solution at pH 8 is significantly higher than that of disodium guanosine-5'-monophosphate, Na(2)(5'-GMP), which supports our earlier hypothesis regarding the importance of cation bridging.