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The electrochemical carbon dioxide reduction reaction (CO 2 RR) is a potential and efficient method that can directly convert CO 2 into high-value-added chemicals under mild conditions. Owing to the exceptionally high activation barriers of CO 2 , catalysts play a pivotal role in CO 2 RR. In this study, the transition metal (TM = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, and Zn) is doped into g-C 3 N 4 with a unique N,O-coordination environment, namely, TM-N 1 O 2 /g-C 3 N 4 . Herein, the catalytic performance and reaction mechanism for the CO 2 RR on TM-N 1 O 2 /g-C 3 N 4 are systematically investigated by density functional theory methods. Especially, through the calculation of Δ G *H and Δ G *COOH /Δ G *OCHO , the catalysts with preference for the CO 2 RR over the hydrogen evolution reaction (HER) are selected for further study. Furthermore, Gibbs free energy computation results of each elementary step for the CO 2 RR on these catalysts indicate that Ti-N 1 O 2 /g-C 3 N 4 has significant catalytic activity and selectivity for reducing CO 2 to methanol (CH 3 OH) with the limiting potential ( U L ) of -0.55 V. Finally, through frontier molecular orbital theory and charge transfer analyses, the introduction of the O atoms illustrates that it is instrumental in regulating the electron distribution of the catalytic active site, thereby improving the catalytic performance. This work provides insight into the design of single-atom catalysts with unique coordination structures for the CO 2 RR.

Low-dimension metal halide perovskites are attractive for bandgap tunable optoelectronic materials. Among them, 1-D CsPbBr 3 quantum wires (QWs) are emerging as promising deep-blue luminescent material. However, the growth dynamics of 1-D perovskite QWs are intricate, making the study and control of 1-D QWs highly challenging. In this study, a strategy for controlling both the length and width of the CsPbBr 3 QWs was realized. The temperature-dependent isotropic growth mechanism was revealed and employed as the main tool for the oriented growth of 1-D CsPbBr 3 QWs for various aspect ratios. Our results pave the way for the controlled synthesis of ultrasmall perovskite nanocrystals.

An efficient synthesis of functionalized 3-acyl-2 H -indazoles via visible-light-induced self-catalyzed energy transfer was developed. This method utilized a self-catalyzed energy transfer process between 2 H -indazoles and α-keto acids, offering advantages like absence of photosensitizers, metal catalysts, and strong oxidants, broad substrate compatibility, and operational simplicity under mild conditions.

Hepatic carcinoma is one of the leading causes of morbidity and mortality among all cancers, but no effective treatment measures have been developed. Herein, polystyrene polysaccharide (PSP) extracted from Polygonatum was used to synthesize gold nanoparticles (PSP-AuNPs) by heating and reduction methods, and the characteristics of the PSP-AuNPs were detected after successful synthesis. In vitro , the immunoregulatory effects of PSP-AuNPs were studied by testing the concentrations of NO, TNF-α, and IL-12p70 in the culture media of PSP-AuNPs-treated RAW264.7 macrophages, and the effect of biocompatibility on the viability of RAW264.7 macrophages and L02 cells was studied via a CCK-8 assay. In vivo , tumor-bearing mice were established and treated with PSP-AuNPs, and the anticancer effects were studied by detecting trends in tumor volume, tumor inhibition rate, and tumor cell proliferation index. Immunoregulation was assessed by evaluating the serum levels of TNF-α and IL-10, the CD4+/CD8+ lymphocyte ratio in peripheral blood and the spleen and thymus indices; toxicity was investigated by measuring body weight, liver and renal function indices. The results showed that PSP-AuNPs could regulate immune function both in vitro and in vivo with almost no toxicity. PSP-AuNPs exhibited excellent anticancer effects on hepatic carcinoma in vivo . The anticancer effect could be strengthened, and the toxicity could be reduced by the combined use of PSP-AuNPs and ADM. In conclusion, PSP-AuNPs could be effective as a therapy and adjuvant therapy for treating hepatic carcinoma, providing potential treatment strategies for this disease., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

3D metal-organic frameworks (MOFs) have gained attention as heterogeneous photocatalysts due to their porosity and unique host-guest interactions. Despite their potential, MOFs face challenges, such as inefficient mass transport and limited light penetration in photoinduced energy transfer processes. Recent advancements in organic photocatalysis have uncovered a variety of photoactive cores, while their heterogenization remains an underexplored area with great potential to build MOFs. This gap is bridged by incorporating photoactive cores into 2D MOF nanosheets, a process that merges the realms of small-molecule photochemistry and MOF chemistry. This approach results in recyclable heterogeneous photocatalysts that exhibit an improved mass transfer efficiency. This research demonstrates a bottom-up synthetic method for embedding photoactive cores into 2D MOF nanosheets, successfully producing variants such as PCN-641-NS, PCN-643-NS, and PCN-644-NS. The synthetic conditions were systematically studied to optimize the crystallinity and morphology of these 2D MOF nanosheets. Enhanced host-guest interactions in these 2D structures were confirmed through various techniques, particularly solid-state NMR studies. Additionally, the efficiency of photoinduced energy transfer in these nanosheets was evidenced through photoborylation reactions and the generation of reactive oxygen species (ROS).

The substituents present upon five-membered bicyclic glucose carbonate monomers were found to greatly affect the reactivities and regioselectivities during ring-opening polymerization (ROP), which contrast in significant and interesting ways from previous studies on similar systems, while also leading to predictable effects on the thermal properties of the resulting polycarbonates. Polymerization behaviors were probed for a series of five five-membered bicyclic 2,3-glucose-carbonate monomers having 4,6-ether, -carbonate, or -sulfonyl urethane protecting groups, under catalysis with three different organobase catalysts. Irrespective of the organobase catalyst employed, regioregular polycarbonates were obtained via ROP of monomers with ether substituents, while the backbone connectivities of polymers derived from monomers with carbonate protecting groups suffered transcarbonylation reactions, resulting in irregular backbone connectivities and broad molar mass distributions. The sulfonyl urethane-protected monomers were unable to undergo organobase-catalyzed ROP, possibly due to the acidity of the proton in urethane functionality. The thermal behaviors of polycarbonates with ether and carbonate pendant groups were investigated in terms of thermal stability and glass transition temperature ( T g ). A two-stage thermal decomposition was observed when tert -butyloxycarbonyl (BOC) groups were employed as protecting side chains, while all other polycarbonates presented high thermal stabilities with a single-stage thermal degradation. T g was greatly affected by side-chain bulkiness, with values ranging from 39 to 139 °C. These fundamental findings of glucose-based polycarbonates may facilitate the development of next-generation sustainable highly functional materials.

Layered two-dimensional Ruddlesden-Popper (RP) halide perovskites are an intriguing class of semiconductors being explored for their linear and nonlinear optical and ferroelectric properties. Second harmonic generation (SHG) is commonly used to screen for noncentrosymmetric and ferroelectric materials. However, SHG measurements of perovskites can be obscured by their intense multiphoton photoluminescence (mPL). Here, we apply multidimensional harmonic generation as a method to eliminate the complications from mPL. By scanning and correlating both excitation and emission frequencies, we unambiguously assess whether a material supports SHG by examining if an emission feature scales as twice the excitation frequency. Measurements of a series of n = 2, 3 RP perovskites reveal that, contrary to previous belief, n -butylammonium (BA) RP perovskites are not SHG-active and thus centrosymmetric, but RP perovskites with phenylethylammonium (PEA) and 2-thiophenemethylammonium (TPMA) spacer cations display SHG. This work establishes multidimensional harmonic generation as a definitive method to measure SHG in halide perovskites.

Ligand binding to the cell surface receptors initiates signaling cascades that are commonly transduced through a protein-protein interaction (PPI) network to activate a plethora of response pathways. However, tools to capture the membrane PPI network are lacking. Here, we describe a cross-linking-aided mass spectrometry workflow for isolation and identification of signal-dependent epidermal growth factor receptor (EGFR) proteome. We performed protein cross-linking in cell culture at various time points following EGF treatment, followed by immunoprecipitation of endogenous EGFR and analysis of the associated proteins by quantitative mass spectrometry. We identified 140 proteins with high confidence during a 2 h time course by data-dependent acquisition and further validated the results by parallel reaction monitoring. A large proportion of proteins in the EGFR proteome function in endocytosis and intracellular protein transport. The EGFR proteome was highly dynamic with distinct temporal behavior; 10 proteins that appeared in all time points constitute the core proteome. Functional characterization showed that loss of the FYVE domain-containing proteins altered the EGFR intracellular distribution but had a minor effect on EGFR proteome or signaling. Thus, our results suggest that the EGFR proteome include functional regulators that influence EGFR signaling and bystanders that are captured as the components of endocytic vesicles. The high-resolution spatiotemporal information of these molecules facilitates the delineation of many pathways that could determine the strength and duration of the signaling, as well as the location and destination of the receptor.

Lead halide perovskite nanocrystals (NCs) have attracted intense attention because of their excellent optoelectronic properties. The ionic nature of halide perovskites makes them highly vulnerable to water. Encapsulation of perovskite NCs with inorganic or organic materials has been reported to enhance their stability; however, they often suffer from large aggregation size, low water solubility, and difficulty for further surface functionalization. Here, we report a facile aqueous process to synthesize water-soluble CsPbBr 3 /Cs 4 PbBr 6 NCs with the assistance of a fluorocarbon agent (FCA), which features a novel mechanism of the perovskite crystallization at the oil/water interface and direct perovskite NCs/FCA self-assembly in an aqueous environment. The products exhibit a high absolute photoluminescence quantum yield (PLQY) of ∼80% in water with the PL lasting for weeks. Through successive ionic layer adsorption and reaction, BaSO 4 was further applied to encapsulate the NCs, which greatly enhanced their stability in phosphate-buffered saline solutions. The high stability in water and saline solution, high PLQY, and tunable emission wavelength, together with the successful demonstration of brain tissue labeling and PL under X-ray excitation, make our perovskite NCs a promising choice for X-ray fluorescent biolabels.

Metal halide perovskite quantum dots (QDs) recently have attracted great research attentions. However, blue-emitting perovskite QDs generally suffer from low photoluminescence quantum yield (PLQY) because of easily formed defects and insufficient surface passivation. Replacement of lead with low toxicity elements is also preferred toward potential commercial applications. Here, we apply Cl-passivation to boost the PLQY of MA 3 Bi 2 Br 9 QDs to 54.1% at the wavelength of 422 nm, a new PLQY record for blue emissive, lead-free perovskite QDs. Because of the incompatible crystal structures between MA 3 Bi 2 Br 9 and MA 3 Bi 2 Cl 9 and the careful kinetic control during the synthesis, Cl - anions are engineered to mainly locate on the surface of QDs acting as passivating ligands, which effectively suppress surface defects and enhance the PLQY. Our results highlight the potential of MA 3 Bi 2 Br 9 QDs for applications of phosphors, scintillators, and light-emitting diodes.

Hierarchical cubelike submicrometer PbS particles consisting of truncated octahedrons, cuboctahedrons, and cubes were prepared in ethylene glycol solution under favorable high mole ratio of thiourea (Tu) to Pb(AC)2 (R(S/Pb)) via a pumping process. A qualitative analysis based on the classical nucleation theory coupled with the crystal growth theory is employed to interpret the observed experimental phenomena. By varying the concentration of reactants, R(S/Pb), and reaction temperature, it is possible to tune the local supersaturation degree (LSD), which is determined by the number of nuclei and overall growth unit (or concentration), surrounding each growing particle that dictates the branching and faceting of PbS particle. Relatively high LSD that is required for branching growth could be achieved at lower concentration of Tu and reaction temperature. Increasing the concentration of Tu and reaction temperature resulted in less LSD and yielded cubic PbS particles.

Sb2Se3 is a promising absorber material for photovoltaic cells because of its optimum band gap, strong optical absorption, simple phase and composition, and earth-abundant and nontoxic constituents. However, this material is rarely explored for photovoltaic application. Here we report Sb2Se3 solar cells fabricated from thermal evaporation. The rationale to choose thermal evaporation for Sb2Se3 film deposition was first discussed, followed by detailed characterization of Sb2Se3 film deposited onto FTO with different substrate temperatures. We then studied the optical absorption, photosensitivity, and band position of Sb2Se3 film, and finally a prototype photovoltaic device FTO/Sb2Se3/CdS/ZnO/ZnO:Al/Au was constructed, achieving an encouraging 2.1% solar conversion efficiency.

Micro- and nanoparticles with high-index facets may exhibit higher chemical activities that are of great importance in practical applications. Cuprite is a potential alternative to expensive noble metals as the catalyst for CO oxidation at moderate temperatures. We report here a solution based approach to the preparation of unusual polyhedral 50-facet Cu2O microcrystals with a morphological yield higher than 70%. It has been revealed that the concentration of OH(-) and the volume ratio of polar organic solvent to water in the mixed solvent play crucial roles in controlling the morphology of Cu2O microcrystals. The formation of the 50 facets could be geometrically viewed as the truncation of all the 24 vertices of a small rhombicuboctahedron having 26 facets. When growing from solutions, however, the anisotropic growth rates along the <100>, <110>, and <111> directions might be responsible for the formation of this morphology. The Miller index of the 24 nearly isosceles trapezoids could be assigned to {311} planes based on geometrical analysis and was verified by simulated models using the WinXmorph software and supported by TEM and ED observations. Compared with other polyhedral Cu2O microcrystals, the as-prepared microcrystals showed a higher specific catalytic rate toward CO oxidation.

The first step of the reaction between DNA and the antitumor drug cisplatin or its clinically inactive isomer transplatin yields monofunctional adducts. Most of the cisplatin monofunctional adducts further react and rather rapidly (t(1/2) smaller than a few hours) to form intrastrand and interstrand cross-links. It is generally accepted that the clinical activity of cisplatin is related to the formation of bifunctional lesions. As concerns transplatin, several studies disagree on the rate of closure of the monofunctional adducts and the nature of the bifunctional lesions. In order to explain these discrepancies, we have prepared several duplexes containing a single monofunctional trans-[Pt(NH3)2(dG)Cl]+ adduct and zero to two monofunctional [Pt(dien)(dG)]2+ adducts at defined positions. In these duplexes, the inert [Pt(dien)(dG)]2+ adducts mimic the presence of transplatin monofunctional adducts. We show that the closure of the transplatin monofunctional adducts is strongly affected by the presence of other adducts and by the length of the duplexes. These findings suggest that the discrepancies in the literature originate from the nature of the platinated samples (molar ratio of bound platinum per nucleotide, length of the DNA fragments). Our general conclusion is that within transplatin-modified DNA, at a low level of platination, the monofunctional adducts evolve slowly (t(1/2) > 24 h) into bifunctional lesions and that these bifunctional lesions are mainly interstrand cross-links. This could explain, at least in part, the clinical inefficiency of transplatin.

In the reaction between trans-diamminedichloroplatinum(II) and single-stranded oligo(2'-O-methyl ribonucleotide)s containing the sequence GNG (N being a nucleotide residue), the 1,3-trans-{Pt-(NH3)2[GNG]} cross-links are formed. The 1,3-intrastrand cross-links are inert within the single-stranded oligonucleotides. By contrast, they rearrange into interstrand cross-links when the platinated oligonucleotides are paired with their complementary RNA strands. The rate of the interstrand cross-linking reaction depends upon the sequence facing the intrastrand cross-links. When the complementary sequences are 5'-CN'C (N' being a nucleotide), the rates are rather slow (T1/2 >/= 3 h at 37 degrees C). The rearrangement of the intrastrand cross-links into interstrand cross-links can be achieved in a few minutes when the triplets facing the intrastrand cross-links are replaced by doublet 5'-UA or 5'-CA. In vitro, the specificity of the cross-linking reaction between a platinated oligo(2'-O-methyl ribonucleotide) and its target sequence (containing the 5'-CA doublet) located within the coding region of Ha-ras mRNA is demonstrated by steric blocking of reverse transcriptase and translation machinery. Within the HBL100ras1 cells, this platinated oligonucleotide binds specifically and irreversibly to the cognate Ha-ras mRNA. It also inhibits the proliferation of the HBL100ras1 cells in a dose-dependent manner. The fast and specific interstrand cross-linking reaction triggered by the formation of a double helix between platinated oligo(2'-O-methyl ribonucleotide)s and RNA enhances the potential of the oligonucleotides which do not induce mRNA cleavage by RNase H, to modulate gene expression by steric blocking of the translation machinery.

The DNA distortion produced by the interstrand cross-link of trans-diamminedichloroplatinum-(II) has been described by means of gel electrophoresis, chemical probes, and molecular mechanics modeling. Synthetic double-stranded oligodeoxyribonucleotides of varying lengths (19-22 base pairs) were synthesized that contained a unique site-specific interstrand cross-link within their central sequence d(TGCT)/d(AGCT) between complementary guanine and cytosine residues. We find that the platinated deoxyriboguanosine residue adopts syn conformation. The duplex is distorted on both sides of the cross-link, but the bases are still paired. The distortion introduces some flexibility into the helix. In addition, the double helix is unwound and bent toward the major groove.

Double-stranded DNA oligomers were constructed to evaluate the effect of bifunctional and monofunctional platinum(II) complexes at the level of DNA transcription. They contained a single lesion, which is either a cis-[Pt(NH3)2(d(GpTpG))] intrastrand cross-link, a trans-[Pt(NH3)2(d(GpTpG))] intrastrand cross-link, a cis-[Pt(NH3)2(d(GpC/GpC))] interstrand cross-link, or a (diethylenetriamine)-platinum(II)-dG adduct. The synthetic duplexes were multimerized and then used as templates in dinucleotide-primed reactions catalyzed by prokaryotic or eukaryotic RNA polymerases. Reactions were conducted in the presence of a single triphosphate substrate (single-step addition reaction) or of a combination of triphosphate substrates, permitting elongation of the trinucleotide products to longer RNA chains (productive elongation reaction), respectively. In transcription of the platinated strands, none of the DNA adducts provided an absolute block to formation of a single phosphodiester bond by either Escherichia coli RNA polymerase or wheat germ RNA polymerase II. However, the single-step addition reactions were much more impeded from transcription of bifunctional adduct-containing templates as compared to those containing monofunctional lesions. Productive elongation was irreversibly blocked in transcription of the platinated strand of templates containing a cis-d(G*pTpG*) intrastrand cross-link or a cis-d(G*pC/G*pC) interstrand cross-link. In both cases transcription stopped at the level of the lesion. Termination occurred also several nucleotides before the elongation complexes reached the interstrand cross-link. A substantial amount of the RNA polymerase molecules was able of bypassing the trans-d(G*pTpG*) cross-links. In all the cases single-step addition reactions were enhanced on the template strand complementary to that containing the intrastrand cross-links.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects on thermal stability and conformation of DNA produced by the monofunctional adducts of chlorodiethylenetriamineplatinum(II) chloride ([Pt(dien)Cl]Cl) have been investigated. Oligodeoxyribonucleotide duplexes of varying lengths (9-20 base pairs) and of varying central trinucleotide sequences were prepared and characterized that contained site-specific and unique N(7)-guanine adducts. Included are adducts at the sequences of d(AGC), d(AGT), d(CGA), d(TGA), d(TGC), and d(TGT). All these monofunctional adducts decrease the melting temperature (Tm) of the duplexes. This destabilization effect exhibits a sequence-dependent variability. The highest lowering of Tm is observed for the modified duplexes containing the central sequence of pyrimidine-guanine-pyrimidine. The destabilization effect is reduced with decreasing concentrations of Na+. Polarography, circular dichroism, phenanthroline-copper, and chemical probes reveal conformational distortions spreading over several base pairs around the adduct. The effects of monofunctional platinum(II) adducts on conformational distortions in DNA exhibit a sequence-dependent variability similar to those on thermal stability of DNA. The influence of the monofunctional adduct formed by cis-diamminemonoaquamonochloroplatinum(II) on the stability of the oligonucleotide duplex has been also studied. This lesion decreases thermal stability of DNA in the same way as does the adduct of [Pt(dien)Cl]Cl.

A 22 base pair double-stranded oligonucleotide containing a unique interstrand adduct resulting from chelation of the two guanine residues within the central sequence d(TGCT/AGCA) by a cis-platinum residue has been studied by means of gel electrophoresis, chemical probes, and molecular mechanics. The anomalously slow electrophoretic mobility of the multimers of the platinated and ligated oligomers suggests that the platinated oligonucleotide is bent. The two cytosine residues (complementary to the platinated guanines) are hyperreactive to hydroxylamine, indicating a large exposure of the two bases to the solvent. The adduct does not induce a local denaturation within the flanking sequences since the adenine residues are not reactive with diethyl pyrocarbonate. This is confirmed by the nonreactivity of the complementary T residues with osmium tetraoxide. These results and the molecular mechanics modeling suggest that the interstrand adduct bends the double helix by approximately 55 degrees toward the major groove, that the double helix conserves its average twist angle, and that the distortion induced by the adduct is localized at the platinated sequence d(GC/CG).

Two duplexes (20-mers) were constructed containing either a single cis-[Pt(NH3)2[d(GpG)]] or cis-[Pt(NH3)2[d(ApG)]] intrastrand cross-link, the major DNA adducts of the antitumor drug cis-diamminedichloroplatinum(II). These synthetic duplexes were multimerized and the resultant polymers used as templates in single-step addition reactions of condensation of a single nucleoside triphosphate substrate to a dinucleotide primer (abortive elongation reaction) catalyzed by prokaryotic or eukaryotic RNA polymerases. Primer-substrate combinations were selected so as to direct trinucleotide product formation within the platinated bases of the templates. Transcription experiments established that cis-DDP-DNA adducts formed at d(ApG) or d(GpG) sites are not an absolute block to formation of a single phosphodiester bond by either Escherichia coli RNA polymerase or wheat germ RNA polymerase II. Furthermore, the kinetic data indicate that single-step addition reactions are much more impeded at the platinated d(GpG) than at the platinated d(ApG) site and that the mechanisms of inhibition of RNA polymerase activity are different at the two platinated sites. In particular, binding affinity between E. coli RNA polymerase and the d(GpG)-containing platinated template is lowered, as the apparent Km of enzyme for the platinated polymer is increased by a factor of 4-5. In contrast, binding affinity between the RNA polymerase and the d(ApG)-containing template is not affected by modification of the d(ApG) site by cis-diamminedichloroplatinum(II). Similar experiments were carried out with synthetic templates containing the adducts at the d(GpG) sites, in which one of the two platinated dG residues is paired with a dT residue.(ABSTRACT TRUNCATED AT 250 WORDS)

We have investigated whether DNA modified at a d(GG) or a d(AG) site by the chemotherapeutic drug cis-diamminedichloroplatinum(II) (cis-DDP) can be used as template by wheat germ RNA polymerase II. The templates used in the present study were obtained by ligation of double-helical oligodeoxyribonucleotides, containing 18 pyrimidine bases and 2 central dG, or dA and dG, bases on one strand and 18 purine bases and 2 central dC, or dT and dC, bases on the complementary strand. Therefore, the cis-DDP adducts are only present on one strand of each of the two templates and are regularly spaced by 18 pyrimidine bases. These constructs allowed us to investigate the effect of cis-DDP on transcription of the platinated strand and of the complementary unplatinated sequence. Transcription experiments were carried out in the presence of dinucleotide primers and either a single triphosphate substrate (abortive elongation) or the full set of triphosphate substrates dictated by the template sequence (productive elongation). The results show that the eucaryotic RNA polymerase can catalyze dinucleotide-primed reactions on platinated DNA. However, the eucaryotic enzyme behaved very differently depending on which strand was transcribed. Thus, transcription elongation was completely blocked on the strand carrying the metal complex, whereas transcription elongation was not blocked on the complementary template strand. However, on this latter strand and with the platinated polymers, productive elongation was slightly inhibited. Furthermore, abortive elongation leading to dinucleotide-primed trinucleotide formation was enhanced on the template strand complementary to that carrying the cis-DDP adducts.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this work was the comparison of the conformational changes induced in the double helix by the adducts formed at d(GG) and d(AG) sites in the reaction between the antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) and DNA. Two duplexes (20-mer) containing either a single d(A*G*) or a single d(G*G) adduct were studied by means of gel electrophoresis and artificial nuclease and chemical probes. It is shown that the d(G*G*) and the d(A*G*) adducts bend DNA similarly, but at the nucleotide level they distort differently the double helix. We suggest that the weaker interactions between platinated A residues and the other nucleotides, as compared to the interactions between platinated G residues and the other nucleotides, are largely responsible for the differences in the distortions induced in DNA by the d(A*G) and d(G*G*) adducts. This suggestion is supported by the study of the distortions induced in duplexes by the d(G*G*) adducts, one of the platinated G residues being paired with a T residue.

The deuteration rates of the poly(dA-dT).poly(dA-dT) amino and imino protons have been measured with stopped-flow spectrophotometry as a function of general and specific base catalyst concentration. Two proton exchange classes are found with time constants differing by a factor of 10 (4 and 0.4 s-1). The slower class represents the exchange of the adenine amino protons whereas the proton of the faster class has been assigned to the thymine imino proton. The exchange rates of these two classes of protons are independent of general and specific base catalyst concentration. This very characteristic behavior demonstrates that in our experimental conditions the exchange rates of the imino and amino protons in poly(dA-dT).poly(dA-dT) are limited by two different conformational fluctuations. We present a three-state exchange mechanism accounting for our experimental results.

Interactions between antibodies to poly(inosinic acid).poly(cytidylic acid) [poly(I).poly(C)] (or Fab fragments) and double-stranded polynucleotides have been studied by several techniques. In quantitative precipitation tests, the amounts of precipitated antibodies depend upon salt concentration. This effect of salt is reversible. From the comparison of the association constants (deduced from fluorescence measurements) for the binding of Fab fragments to several polynucleotides, a direct interaction between atoms or groups of the bases, which can be involved in hydrogen bonds, can be excluded. The complexes between poly(I).poly(C) and Fab fragments interact with ethidium bromide. The association constants for the binding of ethidium bromide to poly(I).poly(C) and to poly(I).poly(C)-Fab fragments complexes are about the same, but Fab fragments reduce the number of base pairs available to ethidium bromide binding. At saturation of poly(I).poly(C) by Fab fragments, the number of binding sites of ethidium bromide is only reduced by a factor of two. It is concluded that all the nucleotide residues covered by the Fab fragment binding site do not interact with the amino acid residues. Circular dichroism studies of the complexes between Fab fragments and polynucleotides are in favor of some conformational change of the polynucleotides.

The purpose of this work was to analyze at the nucleotide level the distortions induced by the binding of cis-diamminedichloroplatinum(II) (cis-DDP) to DNA by means of chemical probes. In order to test the chemical probes, experiments were first carried out on two platinated oligonucleotides. It has been verified by circular dichroism and gel electrophoresis that the binding of cis-DDP to an AG or to a GTG site within a double-stranded oligonucleotide distorts the double helix. The anomalously slow electrophoretic mobility of the multimers of the platinated and ligated oligomers strongly suggests that the platinated oligonucleotides are bent. The reactivity of the oligonucleotide platinated at the GTG site with chloroacetaldehyde, diethyl pyrocarbonate, and osmium tetraoxide, respectively, suggests a local denaturation of the double helix. The 5'G residue and the T residue within the adduct are no longer paired, while the 3'G residue is paired. The double helix is more distorted (but not denatured) at the 5' side of the adduct than at the 3' side. In the case of the oligonucleotide platinated at the AG site, the double helix is also more distorted at the 5' side of the adduct than at the 3' side. The G residue within the adduct is paired. The reactivities of the chemical probes with six platinated DNA restriction fragments show that even at a relatively high level of platination only a few base pairs are unpaired but the double helix is largely distorted. No local denaturation has been detected at the GG sites separated from the nearest GG or AG sites by at least three bases pairs.(ABSTRACT TRUNCATED AT 250 WORDS)

Rabbits were immunized with native DNA modified by the carcinogen N-acetoxy-N-acetyl-2-aminofluorene. The interactions between the purified antibodies to nDNA-AAF (or the Fab fragments) and several ligands have been studied. By radioimmunoassay, nDNA-AAF, dDNA-AAF, and GMP-AAF were found to bind to the antibodies with about the same affinity. GMP-AF interacts slightly less, and GMP and N-OH-AAF do not interact. The values of the association constants deduced from fluorescence measurements for the binding of the Fab fragments to nDNA-AAF, dDNA-AAF, and GMP-AAF, in 50 mM NaCl, pH 7.5, are of the same order of magnitude. The values of the association constants with nDNA-AAF and dDNA-AAF depend upon salt concentration. From this variation; it is deduced that 1-1.5 phosphate groups interact by charge--charge interactions with the Fab fragments. The absorption and circular dischroism spectra of GMP-AAF, nDNA-AAF, and dDNA-AAF bound to the Fab fragments show that the Fab fragments induce similar perturbation to the three ligands. These results lead to the conclusion that the immunodeterminant group is the dGMP-AAF residue.

Antibodies to Z-DNA have been elicited in rabbits immunized with chloro(diethylenetriamine)platinum(II)chloride (Cl2dienPt) modified poly(dG-dC).poly(dG-dC). Under physiological conditions this polynucleotide in which 12% of the bases were substituted is in the Z form. The antibodies are mainly immunoglobulins G as shown by gel filtration of the antiserum and by ultracentrifugation of the antibodies purified on a Sepharose--poly(dG-dC).poly(dG-dC) column. From the quantitative precipitin curve, it is concluded that each binding site of the antibody covers four nucleotide residues. The Z-form DNA-antibody complex is stabilized by electrostatic interactions. There was no interaction between poly(dI-br5dC).poly(dI-br5dC) in the Z form and the antibodies, which strongly suggests that the exocyclic amino group of guanine residues in Z-poly(dG-dC).poly(dG-dC) interacts with the antibody binding site. The modification of poly(dG-dC).poly(dG-dC) by 2-(acetylamino)fluorene residues decreases but does not prevent the binding to the antibodies. It is also shown that the polynucleotide poly(dG-br5dC).poly(dG-br5dC) adopts the Z form over a large range of salt concentration [5 mM tris(hydroxymethyl)aminomethane hydrochloride, pH 7.5, to 3 M NaCl].

In the reaction of cis-diamminedichloroplatinum(II) (cis-DDP) with double-helical (dC-dG)4.(dC-dG)4 or (dC-dG)5.(dC-dG)5, intrastrand and interstrand cross-links between two guanine residues are formed. This is shown by gel electrophoresis in denaturing conditions of the reaction products and by high-performance liquid chromatography (HPLC) analysis of the products digested with nuclease P1. In the reaction of cis-DDP and poly(dG-dC).poly(dG-dC), at relatively low levels of platination, it is mainly interstrand cross-links between two guanine residues that are formed. This is shown by HPLC analysis of the nuclease P1 digest and by gel electrophoresis in denaturing and nondenaturing conditions of the platinated polymer after cleavage with the restriction enzyme HhaI. Moreover, the antibodies to platinated poly(dG-dC).poly(dG-dC) cross-react with the interstrand cross-linked (dC-dG)4 or (dC-dG)5 but not with the intrastrand cross-linked (dC-dG)4 or (dC-dG)5. These antibodies cross-react with platinated natural DNA. The amount of interstrand cross-links deduced from radioimmunoassays (0.5% of the total bound platinum) is lower than that (2%) deduced by gel electrophoresis in denaturing conditions of a platinated DNA restriction fragment. By gel electrophoresis, it is also shown that in vitro the isomer trans-DDP is more efficient in forming interstrand cross-links than cis-DDP.

With the tritium-Sephadex method, the hydrogen-exchange kinetics of the five NH protons of guanine and cytosine residues in Z-form poly(dG-dC) X poly (dG-dC) were measured as a function of temperature and catalyst concentration. Over the measured temperature range from 0 to 34 degrees C, two classes of protons with constant amplitudes are found. The three protons of the fast class, which were assigned to the guanine amino and imino protons, have an exchange half-time in the minute time range (at 20 degrees C the half-time is 2.5 min) and an activation energy of 18 kcal mol-1. Since these two types of protons exchange at the same rate in spite of their grossly different pK values, the exchange of these protons must be limited by the same nucleic acid conformational change. The two cytosine amino protons of the slow class are especially slow with exchange half-times in the hour time range (at 20 degrees C the exchange half-time is 1 h) and the activation energy is 20 kcal mol-1. The exchange of these two protons is not limited by some nucleic acid conformational change as shown by the marked exchange acceleration of these protons upon addition of 0.2 M imidazole. In addition, we have also reexamined the hydrogen-deuterium exchange kinetics of the amino protons of guanosine cyclic 2',3'-monophosphate by a spectral difference method using a stopped-flow spectrophotometer. The measured kinetic process is monophasic with a rate constant of 3 s-1 at 20 degrees C, which is in the same range as the predicted rate constant of the guanine amino protons.(ABSTRACT TRUNCATED AT 250 WORDS)