Bulky Moiety Research Articles

Water soluble quarternizable gallium and indium phthalocyanines bearing quinoline 5-sulfonic acid: Synthesis, aggregation, photophysical and electrochemical studies

Abstract In this work, we have presented the synthesis, characterization, photophysical properties and electrochemical characterization of new tetra α and β-substituted indium and gallium phthalocyanines MPcX(α- or β-HQSA) 4 {M = Ga(III) ( 3 ) ( 4 ) and In(III) ( 5 ) ( 6 ); X = Cl} attached with 1-hydroxy quinoline-5-sulfonic acid groups on non-periphery and their water-soluble quaternized counterpart. The non-periphery substituted phthalocyanines with axially counter chlorine anion exhibit high solubility and low aggregation tendency owing to bulky HQSA steric hindrance moieties. The novel phthalocyanine precursors, 3, 4, 5, 6 synthesis, characterization, photochemical properties (singlet oxygen quantum yields and photodegradation quantum yields) and photophysical properties (fluorescence quantum yields and flouresans behavior) of their peripherally tetra substituted gallium and indium phthalocyanines are reported in this study. The new compounds ( 3, 4, 5, 6 ) have been characterized by using spectroscopic methods, FT-IR, 1 H NMR spectroscopy, electronic spectroscopy and Maldi-TOF spectra in addition to elemental analysis. General trends focus on fluorescence, photodegradation and singlet oxygen quantum yields of these compounds in dimethylsulfoxide (DMSO), water (H 2 O). The nature of the substituent and solvent effect on the photophysical and photochemical parameters of the substituted phthalocyanines ( 3, 4, 5, 6 ) are also reported. The effect of point of substitution on the electrochemical properties of newly synthesized phthalocyanine compounds, periphery (β-) and non-periphery (α-) substituted with 8-hydroxyquinoline-5-sulfonic acid group were evaluated.

Protein stabilization utilizing a redefined codon.

Recent advances have fundamentally changed the ways in which synthetic amino acids are incorporated into proteins, enabling their efficient and multiple-site incorporation, in addition to the 20 canonical amino acids. This development provides opportunities for fresh approaches toward addressing fundamental problems in bioengineering. In the present study, we showed that the structural stability of proteins can be enhanced by integrating bulky halogenated amino acids at multiple selected sites. Glutathione S-transferase was thus stabilized significantly (by 5.2 and 5.6 kcal/mol) with 3-chloro- and 3-bromo-l-tyrosines, respectively, incorporated at seven selected sites. X-ray crystallographic analyses revealed that the bulky halogen moieties filled internal spaces within the molecules, and formed non-canonical stabilizing interactions with the neighboring residues. This new mechanism for protein stabilization is quite simple and applicable to a wide range of proteins, as demonstrated by the rapid stabilization of the industrially relevant azoreductase.

Selection of di(meth)acrylate monomers for low pollution of fluorinated mold surfaces in ultraviolet nanoimprint lithography.

We used fluorescence microscopy to show that low adsorption of resin components by a mold surface was necessary for continuous ultraviolet (UV) nanoimprinting, as well as generation of a low release energy on detachment of a cured resin from a template mold. This is because with low mold pollution, fracture on demolding occurred at the interface between the mold and cured resin surfaces rather than at the outermost part of the cured resin. To achieve low mold pollution, we investigated the radical photopolymerization behaviors of fluorescent UV-curable resins and the mechanical properties (fracture toughness, surface hardness, and release energy) of the cured resin films for six types of di(meth)acrylate-based monomers with similar chemical structures, in which polar hydroxy and aromatic bulky bisphenol moieties and methacryloyl or acryloyl reactive groups were present or absent. As a result, we selected bisphenol A glycerolate dimethacrylate (BPAGDM), which contains hydroxy, bisphenol, and methacryloyl moieties, which give good mechanical properties, monomer bulkiness, and mild reactivity, respectively, as a suitable base monomer for UV nanoimprinting under an easily condensable alternative chlorofluorocarbon (HFC-245fa) atmosphere. The fluorescent UV-curable BPAGDM resin was used for UV nanoimprinting and lithographic reactive ion etching of a silicon surface with 32 nm line-and-space patterns without a hard metal layer.

Beneficial Role of a Bulky Donor Moiety in π-Extended Organic Dyes for Mesoscopic TiO2 Sensitized Solar Cells

This paper reports the spectroscopic and electrochemical characterization of two π-extended D–A−π–A organic dyes, G1 and G2, along with a comparison with their donor-free congeners, DTB-T and DTB-B. A collection of measurements has been carried out to provide insight into the different processes (injection, regeneration, and recombination) involved in the photovoltaic conversion. The study aims, in particular, at rationalizing how the presence of a bulky triarylamine donor group, along with the modification in the chemical structure of the π-bridge, influences the operative cycle of dye-sensitized solar cells. We demonstrated that the donor group contributes to the formation of a more robust organic layer uniformly covering the TiO2 surface, thus decreasing unfavorable charge recombination processes. In addition, the presence of the thiophene sulfur atom in one of the dye π-extensions (G1), by favoring interactions with the triiodide in the electrolyte, triggers detrimental recombination pathways. We conc...

Sialidases as regulators of bioengineered cellular surfaces.

Human sialidases (NEUs) catalyze the removal of N-acetyl neuraminic acids from the glycome of the cell and regulate a diverse repertoire of nominal cellular functions, such as cell signaling and adhesion. A greater understanding of their substrate permissivity is of interest in order to discern their physiological functions in disease states and in the design of specific and effective small molecule inhibitors. Towards this, we have synthesized soluble fluorogenic reporters of mammalian sialidase activity bearing unnatural sialic acids commonly incorporated into the cellular glycocalyx via metabolic glycoengineering. We found cell-surface sialidases in Jurkat capable of cleaving unnatural sialic acids with differential activities toward a variety of R groups on neuraminic acid. In addition, we observed modulated structure-activity relationships when cell-surface sialidases were presented glycans with unnatural bulky, hydrophobic or fluorinated moieties incorporated directly via glycoengineering. Our results confirm the importance of cell-surface sialidases in glycoengineering incorporation data. We demonstrate the flexibility of human NEUs toward derivatized sugars and highlight the importance of native glycan presentation to sialidase binding and activity. These results stand to inform not only metabolic glycoengineering efforts but also inhibitor design.

Gas permeation properties of poly(sulfone-co-ethylene glycol) membranes containing bis(phenyl)fluorene moieties

Copolymers based on glassy and rubbery units have been developed to take advantages of both domains to enhance solubility and diffusivity. Well-tuned microstructure in copolymers has provided high gas permeability and selectivity. In this study, we report on the syntheses and characterizations of copolymers using poly(ethylene glycol) and high free volume polysulfone. Bulky and flexible bis(phenyl)fluorene moiety is introduced in polysulfone domain. Comparison between conventional bisphenol-A based polysulfone and the polysulfone in this work is made in terms of fractional free volume and gas permeation properties. In the poly(sulfone-co-ethylene glycol), the composition of sulfone/ethylene glycol results in the improvement of thermal and physical properties. Copolymers are characterized using gel permeation chromatography, thermogravimetric analysis, differential scanning calorimetry, wide angle X-ray diffraction, and gas permeation measurements.

Influence of the linkage type and functional groups in the carcinogenic moiety on the conformational preferences of damaged DNA: structural and energetic characterization of carbon- and oxygen-linked C(8)-phenolic-guanine adducts.

Computational (DFT, MD, and free energy) methods are used to systematically compare the structural and energetic properties of C(8)-bonded 2'-deoxyguanosine (dG) adducts derived from phenolic toxins, namely, the oxygen-linked (unsubstituted) adduct ((PhO)dG) and carbon-linked adducts ((ortho-PhOH)dG or (para-PhOH)dG) that contain a hydroxyl group in the bulky moiety. Despite restricted rotation at the C(8)-X bond due to the presence of the oxygen linker, the (PhO)dG adduct likely possesses the greatest glycosidic (anti/syn) conformational flexibility at the 5'-terminus of DNA. However, the anti/syn energy difference is the smallest for the (para-PhOH)dG nucleotide at other helical positions, which correlates with the greatest conformational heterogeneity for the corresponding (NarI) adducted DNA. Most importantly, the total number of accessible conformations of adducted DNA depend on the phenolic adduct considered. Specifically, although the only conformations accessible to (PhO)dG adducted DNA correspond to the anti adduct glycosidic orientation, the C-linked adducts can also adopt the syn orientation in the double helix. Moreover, the number of accessible conformations for DNA containing the C-linked adducts depends on the nature of discrete interactions involving the hydroxyl group in the C(8)-moiety. In fact, such interactions lead to a novel (intercalated) conformational theme in the case of the (para-PhOH)dG adduct. Together, these results indicate that the type of C(8)-linkage, and the presence and location of additional functional groups in the bulky moiety affect the conformational outcomes, which adds to the list of previously established effects including the size of the carcinogenic moiety, adduct ionization state, and sequence context on the conformational preferences of damaged DNA. Most importantly, our study provides valuable structural information that explains the experimentally observed mutagenic potential of DNA phenolic adducts and predicts the relative repair propensity of the three phenolic lesions.

Efficiency Improvement of Dye-Sensitized Solar Cells with Surface-Modified Photoelectrodes.

A novel surface modifier, ethylenediamine tetraacetic acid tetrasodium salt (EDTNa), was incorporated on the surface of TiO2, and the resulting electrodes were applied to the photoanode of dye-sensitized solar cells (DSSCs). The DSSC with EDTNa-incorporated photoelectrode showed an increase in short-circuit current (JSC) and open-circuit voltage (VOC), resulting in a 16.5% enhancement in power conversion efficiency, compared to that of reference cell without EDTNa. It was found that the presence of the bulky ethylenediamine tetraacetate moieties increases lifetime of electrons injected from dye molecules to TiO2, resulting from an effective prevention of direct contact between electrolyte ions and the TiO2 surface. This improvement of lifetime induced the enhancement in J, and VOC.

Influence of benzene ring number attached on non-conjugated 3,4-ethylenedioxythiophene derivatives for solid-state polymerization

We chose the three-atom linker EDOT–CH2–N(R)–CH2–EDOT as a large platform to determine boundary conditions through the introduction of a rigid or bulky moiety and to accurately control the SSP behavior.

The Role of the Threading Moiety in DNA Threading Intercalation by Ruthenium Dimer Complexes

There is significant interest in ruthenium dimer complexes due to their novel DNA binding properties. The binuclear ruthenium complex ΔΔ-[μ-bidppz(bipy)4Ru2]4+ that we investigate in this study binds to DNA by threading intercalation, in which one of the bulky ruthenium moieties threads through the DNA base pair stack to reach its bound state. The extremely slow dissociation from DNA of this threading intercalator gives it properties needed for chemotherapy drugs, while also making it difficult to study in traditional bulk experiments. In this study we use optical tweezers in order to quantify the threading kinetics as well as the equilibrium behavior of this ruthenium dimer complex to understand how changing the ancillary ligands coordinated to ruthenium (threading moiety) affects the process of threading. To observe the slow threading process, the DNA was held at a constant force in the presence of the ligand and the DNA extension was measured as a function of time until the extension reached equilibrium. When the concentration of the ligand is increased during these constant force measurements, the total extension of the DNA will also increase until it becomes saturated at some concentration as all of the ligand binding sites are filled. These measurements of the equilibrium DNA extension allow for a full quantitative description of the binding kinetics and equilibrium behavior of the complex. The preliminary data suggests that the ΔΔ-[μ-bidppz(bipy)4Ru2]4+ complex with its bicyclic bipyridine ligand, shows significantly faster kinetics compared to the ΔΔ-[μ-bidppz(phen)4Ru2]4+, complex with a tricyclic phenanthroline ligand counterpart.

Lone pair-π interaction-induced generation of non-interpenetrated and photochromic cuboid 3-D naphthalene diimide coordination networks.

Interpenetration is an intrinsic behaviour for the porous coordination networks. To prevent the interpenetration, a common strategy is the imposition of geometric or steric restrictions by incorporating bulky moieties into organic tectons. So far, most of the available incorporations have been achieved through a covalent connection, while few involved in the non-covalent weak interactions. In this paper, we have reported that such interpenetration can be prevented by the less common lone pair-π interactions. By imposing the lone pair-π interactions through the addition of lone-pair-bearing N-methylpyrrolidin-2-one or iodine, combinations of rigid naphthalene diimide tectons bearing two divergently oriented pyridyl units at both imide extremities with ZnSiF6 led to non-interpenetrated cuboid 3-D coordination networks that should have been interpenetrated. In addition, such close-contacting lone pair-π interactions between electron donors and acceptors have also been demonstrated to play a key role in their photochromic properties.

Regioregular Organoborane-Functionalized Poly(3-alkynylthiophene)s

In our quest to develop regioregular borane acceptor-modified thiophene polymers, we prepared a series of new alkynylphenylborane-functionalized monomers and explored their polymerization. The regioregular polymer rr-P1 and an alternating copolymer with 3-hexylthiopene, rr-P2, were successfully obtained by Stille-type polymerization. An X-ray crystal structure of the bithiophene model system 2-Br revealed coplanar thiophene rings and the formation of π-stacks, despite the presence of bulky dimesitylborane moieties. For the polymers, rr-P1 showed the most bathochromic absorption (520 nm) and emission bands (620 nm), indicating the importance of high regioregularity and the beneficial effect of alkynyl relative to alkyl pendent groups. A higher energy absorption at ca. 340 nm could be assigned to charge transfer to the borane pendent groups based on DFT calculations on molecular model compounds that mimic the polymer repeat units. This assignment was further supported by fluoride anion binding studies.

Polycondensation of structurally divergent tetraamine monomers with dicarboxylic acids to synthesize polybenzimidazole copolymers for polymer electrolyte membranes

AbstractIn our effort to promote 2,6‐bis(3,4‐diaminophenyl)‐4‐phenylpyridine (Py‐TAB) as an alternative tetraamine monomer to conventionally used 3,3′,4,4′‐tetraaminobiphenyl (TAB) for synthesizing readily processable pyridine bridged polybenzimidazoles (Py‐PBIs), two series of random copolymers (PBI‐co‐Py‐PBI) were synthesized by polymerizing Py‐TAB and TAB with isophthalic acid or terephthalic acid to produce meta (mPBI‐co‐mPy‐PBI) and para (pPBI‐co‐pPy‐PBI) connected copolymers, respectively. For the first time in the PBI literature, copolymers were synthesized by varying the relative compositions of tetraamines (TAB and Py‐TAB) in the polymerization feed with a single dicarboxylic acid (DCA) instead of the traditionally used method where two DCAs with variable compositions were polymerized with a single tetraamine. The solubility and hence the processability of the copolymers were improved significantly upon introduction of Py‐PBI in the copolymer. The detailed characterizations of both meta and para series copolymers compellingly established that thermal, chemical and mechanical stabilities can be easily modulated according to need by altering the relative compositions of PBI and Py‐PBI. The phosphoric acid (PA) loading of the copolymers increased gradually with increasing Py‐PBI content since the bulky pyridine moiety facilitated the absorption of PA. The presence of pyridine functionality and a larger PA loading caused a higher proton conductivity of PA doped copolymer membranes. © 2014 Society of Chemical Industry

A theoretical and experimental study of the effects of silyl substituents in enantioselective reactions catalyzed by diphenylprolinol silyl ether.

The effect of silyl substituents in diphenylprolinol silyl ether catalysts was investigated. Mechanistically, reactions catalyzed by diphenylprolinol silyl ether can be categorized into three types: two that involve an iminium ion intermediate, such as for the Michael-type reaction (type A) and the cycloaddition reaction (type B), and one that proceeds via an enamine intermediate (type C). In the Michael-type reaction via iminium ions (type A), excellent enantioselectivity is realized when the catalyst with a bulky silyl moiety is employed, in which efficient shielding of a diastereotopic face of the iminium ion is directed by the bulky silyl moiety. In the cycloaddition reaction of iminium ions (type B) and reactions via enamines (type C), excellent enantioselectivity is obtained even when the silyl group is less bulky and, in this case, too much bulk reduces the reaction rate. In other cases, the yield increases when diphenylprolinol silyl ethers with bulky substituents are employed, presumably by suppressing side reactions between the nucleophilic catalyst and the reagent. The conformational behaviors of the iminium and enamine species have been determined by theoretical calculations. These data explain the effect of the bulkiness of the silyl substituent on the enantioselectivity and reactivity of the catalysts.

A monofunctional platinum(II)-based anticancer agent from a salicylanilide derivative: Synthesis, antiproliferative activity, and transcription inhibition

Cationic monofunctional platinum(II)-based anticancer agents with a general formula of cis-[Pt(NH3)2(N-donor)Cl]+ have recently drawn significant attention due to their unique mode of action, distinctive anticancer spectrum, and promising antitumor activity both in vitro and in vivo. Understanding the mechanism of action of novel monofunctional platinum compounds through rational drug design will aid in the further development of active agents. In this study, we synthesized and evaluated a monofunctional platinum-based anticancer agent SA–Pt containing a bulky salicylanilide moiety. The antiproliferative activity of SA–Pt was close to that of cisplatin. Mechanism studies revealed that SA–Pt entered HeLa cells more efficiently than cisplatin, blocked the cell cycle at the S-phase, and induced apoptosis. The compound bound to DNA as effectively as cisplatin, but did not block RNA polymerase II-mediated transcription as strongly as cisplatin, indicating that once the compound formed Pt-DNA lesions, the salicylanilide group was more easily recognized and removed. This study not only enriches the family of monofunctional platinum-based anticancer agents but also guides the design of more potent monofunctional platinum complexes.

Abstract 4302: The development study of hypoxia responsive chemiluminescent probe for tumor hypoxia imaging

Abstract Introduction: The tumor microenvironment is recognized as a major factor that influences not only the response to conventional anticancer therapies but also the potential for malignant progression and metastasis. Therefore, it is considered that tumor hypoxia imaging is critical for cancer diagnosis and therapy. As optical modalities offer the advantages of non-invasive, easy-to-handle, and cost-effective imaging, much effort has been done to develop synthetic fluorescent imaging probes for tumor hypoxia. In particular, we focus our attention on chemiluminescence imaging which can avoid interference from tissue autofluorescence and scattering light. We therefore show the development of hypoxia responsive chemiluminescent probe, which has the advantage of lower detection limits and improved signal-to-noise ratio compared to existing fluorescent probes. Results and discussion: In our molecular design, luminescence is derived from 1,2-dioxetane cleavage triggered by hypoxia-selective enzymatic reduction of electron-deficient aromatics. At the start, nitrobenzyl moiety was chosen as a bioreductively cleavable protective group linked to 1,2-dioxetane moiety through phenyl ether linker to construct synthetic probe NB-Adm. The compound was synthesized from 2-adamantanone in 19% (overall yield, 6 steps). Then NB-Adm was attempted to be reduced by nitroreductase, however, no luminescence was observed. HPLC analysis of the reaction mixture indicated that our expected reduction did not occur, probably because bulky adamantane moiety prevented the enzymatic reaction owing to steric hindrance. Therefore, a self-immolative linker was employed to keep away 1,2-dioxetane moiety from enzyme recognition moiety. In this time, quinone moiety was chosen as a protective group which was expected to be better substrate than nitrophenyl one in terms of their redox potential. This newly designed compound, TMQ-Adm was synthesized from 2-adamantanone in 16% (overall yield, 6 steps). By the use of TMQ-Adm, we successfully observed luminescent emission from the reaction with nitroreductase. This implied that our bioredctively activatable probe can be applicable for chemiluminescence imaging for tumor hypoxia. Now we are investigating to develop chemiluminescent probe to realize in vivo imaging of tumor hypoxia by improving luminescent quantum yield under physiological condition. Citation Format: Kensuke Okuda, Toru Ban, Tasuku Hirayama, Hideko Nagasawa. The development study of hypoxia responsive chemiluminescent probe for tumor hypoxia imaging. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4302. doi:10.1158/1538-7445.AM2014-4302

Mixed amido-/imido-/guanidinato niobium complexes: synthesis and the effect of ligands on insertion reactions.

The new monoguanidinato complexes [Nb(NMe2)2{N(2,6-(i)Pr2C6H3)}{(NR)(NR')C(NMe2)}] (R = R' = (i)Pr, 2; R = (t)Bu, R' = Et, 3) were obtained by the insertion reaction of either diisopropylcarbodiimide or 1-tert-butyl-3-ethylcarbodiimide with the triamido precursor [Nb(NMe2)3(N-2,6-(i)Pr2C6H3)] (1) bearing a bulky imido moiety. The μ-oxo derivative [{N(2,6-(i)Pr2C6H3)}{(N(i)Pr)2C(NMe2)}(NMe2)Nb]2(μ-O) (2a) was formed by an unexpected hydrolysis reaction of the amido niobium compound 2. Alternatively, monoguanidinato complexes [Nb(NMe2)2{N(2,6-(i)Pr2C6H3)}{(N(i)Pr)2C(NHR)}] (R = (i)Pr, 4, (n)Bu, 5) can be obtained by protonolysis of 1 with N,N',N''-alkylguanidines [(NH(i)Pr)2C(NR)] (R = (i)Pr, (n)Bu). Compound also reacts with either tert-butylisocyanide or 2,6-xylylisocyanide to give, by a migratory insertion reaction, the corresponding iminocarbamoyl compounds [Nb(NMe2)2{(NMe2)C=NR}{N(2,6-(i)Pr2C6H3)}] (R = (t)Bu, 6, Xy, 7). Addition of the neutral alkylguanidines to complex 6 results in a facile C-N bond cleavage at room temperature in a process directed by the formation of the stable chelate complex 4 or 5. Complex reacts with heterocumulenic CS2 to produce new imido dithiocarbamato complexes [Nb(NMe2){S2C(NMe2)}2{N(2,6-(i)Pr2C6H3)}] (8) and [Nb{S2C(NMe2)}3{N(2,6-(i)Pr2C6H3)}] (9). These complexes do not react with alkylguanines, although new mixed guanidinato dithiocarbamato complexes [Nb(NMe2){S2C(NMe2)}{(N(i)Pr)2C(NHiPr)}{N(2,6-(i)Pr2C6H3)}] (10) and [Nb{(S2C(NMe2)}2{(N(i)Pr)2C(NH(i)Pr)}{N(2,6-(i)Pr2C6H3)}] (11) can be obtained by reaction of complex 4 with one or two equivalents of CS2, respectively. All of the complexes were characterized spectroscopically and the dynamic behaviour of some of them was studied by variable-temperature NMR. The molecular structures of 2a, 3, 6 and 10 were also established by X-ray diffraction studies.

The influence of the leaving iodine atom on phyllosilicate syntheses and useful application in toxic metal removal with favorable energetic effects

Novel nanostructured 2:1 hybrid cobalt and nickel phyllosilicates containing attached diethyl iminodiacetate moieties within the interlamellar spaces were synthesized using a mild non-hydrothermal sol–gel methodology. The organofunctionalization of these hybrids was achieved using silylating agents formed by the reaction of 3-chloropropyltriethoxysilane or 3-iodopropyltrietoxysilane with diethyl iminodiacetate, whereas 3-iodopropyltriethoxysilane was synthesized from the reaction of 3-chloropropyltriethoxysilane with NaI. The degrees of functionalization of the new materials are associated with the nucleophilic displacement of the halide atom by the nitrogen basic center of diethyl iminodiacetate during the silylating agents' syntheses. The incorporation of an iodine atom favored the introduction of bulky basic moieties in the pendant chain. For example, the degree of functionalization for the nickel phyllosilicate functionalized from 3-iodopropyltriethoxysilane, (1.83 ± 0.01) mmol g−1, was higher than that of the nickel phyllosilicate functionalized from 3-chloropropyltriethoxysilane, (0.59 ± 0.02) mmol g−1. Infrared spectroscopy combined with 13C and 29Si NMR spectroscopy confirmed the attachment of organic moieties covalently bonded to the silicon sheet network, and the lamellar 2:1 trioctahedral phyllosilicate structures were confirmed by XRD. Further characterization was provided by thermogravimetry, SEM and TEM, which exhibited thermally stable hybrids presenting well-formed particles with a homogeneous distribution of cobalt, nickel, and nitrogen. The attached basic centers have the ability to sorb lead and cadmium from aqueous solution. The sorption data fit the Langmuir model and indicated maximum lead sorption values of (2.11 ± 0.16) mmol g−1 for the cobalt phyllosilicate functionalized from 3-iodopropyltriethoxysilane and (1.99 ± 0.11) mmol g−1 for the hybrid prepared from 3-chloropropyltriethoxysilane, for example, reflecting the higher degree of functionalization of the former. All of the other hybrids exhibited the same tendency, even for cadmium sorption. The thermodynamic data obtained from calorimetric titration revealed the spontaneity of these chelating interactive processes, which are enthalpically and entropically favorable for the proposed cation-basic center interactions at the solid–liquid interface.

Complex Conformational Heterogeneity of the Highly Flexible O6-Benzyl-guanine DNA Adduct

The conformational preference of the O6-benzyl-guanine (BzG) adduct was computationally examined using nucleoside, nucleotide, and DNA models, which provided critical information about the potential mutagenic consequences and toxicity of the BzG adduct in our cells. Substantial conformational flexibility of the BzG moiety, including rotation of the bulky group with respect to the base and the internal conformation of the bulk moiety, is seen in the nucleoside and nucleotide models. This large conformational flexibility suggests the conformation adopted by BzG is dependent on the local environment of the BzG adduct. Upon incorporation of the adduct into the DNA helix, the BzG conformational flexibility is maintained. The range of BzG conformations adopted in DNA likely arises due to a combination of the long and flexible (-CH2-) linker, the small adduct size, and the lack of discrete interactions between the bulky moiety and G. Because of the conformational flexibility of the adduct, many DNA conformations are observed for BzG adducted DNA, including those not previously reported in the literature, and thus, a modified nomenclature for adducted DNA conformations is presented. Furthermore, the preferred conformation of BzG adducted DNA is greatly dependent on a number of factors, including the pairing nucleotide, the discrete interactions in the helix, and the solvation of the benzyl moiety. These factors in turn lead to a complicated mutagenic and toxic profile that may invoke pairing with natural C, mispairs, or deletion mutations, which is supported by previously reported experimental biochemical studies. Despite this complex mutagenic profile, pairing with C leads to the most stable helical structure, which is the first combined structural and energetic explanation for experimental studies reporting a higher rate of C incorporation than any other nucleobase upon BzG replication.

ChemInform Abstract: Titanium‐Mediated Addition of Grignard Reagents to Acyl Cyanohydrins: Aminocyclopropane versus 1,4‐Diketone Formation.

ChemInformVolume 45, Issue 26 Preparative Organic Chemistry ChemInform Abstract: Titanium-Mediated Addition of Grignard Reagents to Acyl Cyanohydrins: Aminocyclopropane versus 1,4-Diketone Formation. Paul Setzer, Paul Setzer Inst. Mol. Materiaux Mans, CNRS, Univ. Maine, F-72085 Le Mans, Fr.Search for more papers by this authorGwenael Forcher, Gwenael Forcher Inst. Mol. Materiaux Mans, CNRS, Univ. Maine, F-72085 Le Mans, Fr.Search for more papers by this authorFabien Boeda, Fabien Boeda Inst. Mol. Materiaux Mans, CNRS, Univ. Maine, F-72085 Le Mans, Fr.Search for more papers by this authorMorwenna S. M. Pearson-Long, Morwenna S. M. Pearson-Long Inst. Mol. Materiaux Mans, CNRS, Univ. Maine, F-72085 Le Mans, Fr.Search for more papers by this authorPhilippe Bertus, Philippe Bertus Inst. Mol. Materiaux Mans, CNRS, Univ. Maine, F-72085 Le Mans, Fr.Search for more papers by this author Paul Setzer, Paul Setzer Inst. Mol. Materiaux Mans, CNRS, Univ. Maine, F-72085 Le Mans, Fr.Search for more papers by this authorGwenael Forcher, Gwenael Forcher Inst. Mol. Materiaux Mans, CNRS, Univ. Maine, F-72085 Le Mans, Fr.Search for more papers by this authorFabien Boeda, Fabien Boeda Inst. Mol. Materiaux Mans, CNRS, Univ. Maine, F-72085 Le Mans, Fr.Search for more papers by this authorMorwenna S. M. Pearson-Long, Morwenna S. M. Pearson-Long Inst. Mol. Materiaux Mans, CNRS, Univ. Maine, F-72085 Le Mans, Fr.Search for more papers by this authorPhilippe Bertus, Philippe Bertus Inst. Mol. Materiaux Mans, CNRS, Univ. Maine, F-72085 Le Mans, Fr.Search for more papers by this author First published: 12 June 2014 https://doi.org/10.1002/chin.201426056Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume45, Issue26July 1, 2014 RelatedInformation