Cubic PtRh alloys supported on graphene (PtxRhy/GN) with different atomic ratio of Pt and Rh were directly synthesized for the first time using the modified polyol method with Br(-) for the shape-directing agents. The process didn't use surface-capping agents such as PVP that easily occupy the active sites of electrocatalysts and are difficult to remove. Graphene is the key factor for cubic shape besides Br(-) and keeping catalysts high-dispersed. The X-ray diffraction (XRD), scanning electron microscope (SEM) and transmission electron microscope (TEM) were used to characterize the structure and morphology of these electrocatalysts. The results showed that they were composed of homogeneous cubic PtRh alloys. Traditional electrochemical methods, such as cyclic voltammetry and chronoamperometry, were used to investigate the electrocatalytic properties of PtxRhy/GN towards ethanol electrooxidation. It can be seen that PtxRhy/GN with all atomic ratios exhibited high catalytic activity, and the most active one has a composition with Pt : Rh = 9 : 1 atomic ratio. Electrochemical in situ FTIR spectroscopy was used to evaluate the cleavage of C-C bond in ethanol at room temperature in acidic solutions, the results illustrated that Rh in an alloy can promote the split of C-C bond in ethanol, and the alloy catalyst with atomic ratio Pt : Rh = 1 : 1 showed obviously better performance for the C-C bond breaking in ethanol and higher selectivity for the enhanced activity of ethanol complete oxidation to CO2 than alloys with other ratios of Pt and Rh. The investigation indicates that high activity of PtxRhy/GN electrocatalyst towards ethanol oxidation is due to the specific shape of alloys and the synergistic effect of two metal elements as well as graphene support.

The interactions of PT-ACRAMTU, a cytotoxic platinum-acridine conjugate, with the human telomeric G-quadruplex have been studied using in-line high-performance liquid chromatographymass spectrometry and footprinting assays. The conjugate reacts significantly faster with quadruplex DNA (t 1/2 = 1.2 h) than with double-stranded DNA, and A-N7, and not G-N7, is the kinetically preferred target, an unprecedented reactivity feature in platinum-DNA interactions. Unlike the clinical platinum drug cisplatin, which targets the human telomeric sequence nonspecifically, the platinum-intercalator technology has the potential to produce telomere-specific anticancer agents via a mechanism that kinetically discriminates between G and A in the two DNA secondary structures.Human telomeres consist of noncoding repeats of the guanine (G)-rich sequence 5′-TTAGGG, which protect chromosomes from degradation and end fusion, two factors limiting a normal cell's life span. 1 In most tumors, the telomeres are relatively short compared to normal cells, but are efficiently maintained by up-regulated telomerase, rendering cancer cells immortal. 2 It has been proposed that telomere-targeted agents capable of disrupting indefinite cell proliferation might have applications as anticancer therapeutics. 2 Telomeres contain 3′ singlestranded overhangs, which have the potential to fold into G-quadruplex structures containing three π-stacked G tetrads (G4). In a G tetrad, the four guanine bases are linked by Hoogsteen H-bonding. 3 In this configuration, N7 of guanine is protected from DNA-targeted electrophilic agents, such as platinum-containing drugs, which preferentially bind to this site.Our previous discovery of the unusual high frequency of monofunctional adenine (A) adducts in double-stranded DNA formed by PT-ACRAMTU (ACRAMTU = 1-[2-(acridin-9-ylamino) ethyl]-1,3-dimethylthiourea) ( Figure 1A), a platinating-intercalating cytotoxic hybrid agent, 4 prompted us to study its interactions with the sequence 5′-TTAGGG in a quadruplex secondary structural context. On the basis of high-resolution 5 and biophysical 6 data available for human telomere sequences, we anticipated that specific adenine bases in the flexible TTA loop regions of the quadruplex might be targeted by PT-ACRAMTU. The current study demonstrates that telomeric A is not only highly susceptible to platination by this agent, but binding to A-N7 is kinetically favored over adduct formation with G-N7. This is an E-mail: bierbau@wfu.edu. ] (ss-6), were also studied. The base and donor-site specificity of platination in G4-22 (as well as in ds-22 and ss-6) was deduced from the LC-MS analysis of fragments detected in the enzymatic and acidic digests. Structural assignments were based on molecular masses and characteristic fragmentation patterns observed in positive-and negative-mode ESMS and tandem MS/MS spectra (Supporting Information). NIH Public AccessFour fragments were observed in the enzymatic digests of drug-modified G4-22, all of which could be unambiguously identified: 2′...

A restriction enzyme cleavage inhibition assay was designed to determine the rates of DNA platination by four non-cross-linking platinum-acridine agents represented by the formula [Pt(am 2 )LCl](NO 3 ) 2 , where am is a diamine nonleaving group and L is an acridine derived from the intercalator 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea (ACRAMTU). The formation of monofunctional adducts in the target sequence 5′-CGA was studied in a 40-base-pair probe containing the EcoRI restriction site GAATTC. The time dependence of endonuclease inhibition was quantitatively analyzed by polyacrylamide gel electrophoresis. The formation of monoadducts is approximately 3 times faster with double-stranded DNA than with simple nucleic acid fragments. Compound 1 (am 2 is ethane-1,2-diamine, L is ACRAMTU) reacts with a first-order rate constant of k obs = 1.4 ± 0.37 × 10 −4 s −1 (t 1/2 = 83 ± 22 min). Replacement of the thiourea group in ACRAMTU with an amidine group (compound 2) accelerates the rate by fourfold (k obs = 5.7 ± 0.58 × 10 −4 s −1 , t 1/2 = 21 ± 2 min), and introduction of a propane-1,3-diamine nonleaving group results in a 1.5-fold enhancement in reactivity (compound 3, k obs = 2.1 ± 0.40 × 10 −4 s −1 , t 1/2 = 55 ± 10 min) compared with the prototype. Derivative 4, containing a 4,9-disubstituted acridine threading intercalator, was the least reactive compound in the series (k obs = 1.1 ± 0.40 × 10 −4 s −1 , t 1/2 = 104 ± 38 min). The data suggest a correlation may exist between the binding rates and the biological activity of the compounds. Potential pharmacological advantages of rapid formation of cytotoxic monofunctional adducts over the common purine-purine cross-links are discussed.

The interactions of a newly synthesized platinum-modified perylene derivative, compound 7 ([{Pt(dien)}2(μ-4-S,S')](NO3)4 (dien = diethylenetriamine, 4 = N,N'-bis(1-(2-aminoethyl)-1,3-dimethylthiourea)-3,4,9,10-perylenetetracarboxylic acid diimide), with the human telomeric repeat were studied using various model oligo(deoxy)ribonucleotides to mimic the polymorphic nature of the telomeric G-quadruplex. UV/visible spectroscopy, CD spectropolarimetry, electrospray mass spectrometry (ES-MS), and isothermal titration calorimetry (ITC) were used to demonstrate that compound 7 selectively recognizes the antiparallel form of the unimolecular telomeric G-quadruplex formed by the sequence d(TTAGGG)4 (dG-24), to which it binds with a 2:1 stoichiometry and nanomolar affinity. Compared with telomeric DNA, the first binding event of compound 7 in titrations with the RNA quadruplex formed by r(UUAGGG)4 (rG-24) is an order of magnitude weaker. Compound 7 does not induce the antiparallel G-quadruplex RNA, which invariably exists in a parallel form and dimerizes in solution. Based on the cumulative experimental data, two distinct mechanisms are proposed for the recognition of G-quadruplex DNA and RNA by compound 7. Potential biomedical and biochemical applications of the platinum–perylene technology are discussed.

The reactivity of two DNA-targeted platinum-acridine conjugates with cysteine sulfur was studied. The conjugate containing an amidine-NH donor group cis to the chloride leaving group showed considerably reduced reactivity with N-acetylcysteine compared to the prototypical derivative containing a thiourea-S linkage. The opposite scenario has been observed previously in reactions with nucleobase nitrogen. Possible consequences of the unique target-selective tuning of the substitution chemistry for the pharmacodynamic properties and biological activity of these agents are discussed.