Publications by authors named "Graham E Ball"

36 Publications

Binding methane to a metal centre.

Nat Chem 2022 Apr 25. Epub 2022 Apr 25.

School of Chemistry, UNSW Sydney, Sydney, NSW, Australia.

The σ-alkane complexes of transition metals, which contain an essentially intact alkane molecule weakly bound to the metal, have been well established as crucial intermediates in the activation of the strong C-H σ-bonds found in alkanes. Methane, the simplest alkane, binds even more weakly than larger alkanes. Here we report an example of a long-lived methane complex formed by directly binding methane as an incoming ligand to a reactive organometallic complex. Photo-ejection of carbon monoxide from a cationic osmium-carbonyl complex dissolved in an inert hydrofluorocarbon solvent saturated with methane at -90 °C affords an osmium(II) complex, [η-CpOs(CO)(CH)], containing methane bound to the metal centre. Nuclear magnetic resonance (NMR) spectroscopy confirms the identity of the σ-methane complex and shows that the four protons of the metal-bound methane are in rapid exchange with each other. The methane ligand has a characteristically shielded H NMR resonance (δ -2.16), and the highly shielded carbon resonance (δ -56.3) shows coupling to the four attached protons (J = 127 Hz). The methane complex has an effective half-life of about 13 hours at -90 °C.
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http://dx.doi.org/10.1038/s41557-022-00929-wDOI Listing
April 2022

Molecular dynamic simulations of diacridine binding to DNA: Indications that C6 diacridine can bisintercalate spanning two base pairs.

Biopolymers 2021 Apr 18;112(4):e23409. Epub 2020 Nov 18.

School of Chemistry, UNSW Sydney, Sydney, New South Wales, Australia.

Dimers of 9-aminoacridine linked via the 9-amino group with polymethylene chains, termed diacridines, are known to bisintercalate into DNA when the linker comprises 6 or more methylene units. There are no literature reports of crystal or NMR solution structures for bisintercalated diacridine-DNA complexes, and the issue of the structure of the C6 ([CH ] linker where n = 6) diacridine complex remains unresolved. Previously, based on simple geometric considerations, it was proposed that C6 diacridine could only span a single base pair, which requires that its bifunctional reaction violates the widely-observed "neighbor exclusion principle" where bound intercalators are separated by at least 2 base pairs. Here we have explored the structure of diacridine-DNA complexes using unrestrained molecular dynamics in explicit solvent using the parmbsc0 forcefield in AMBER14. We studied the C4 to C8 dimers, intercalated via both the minor and major DNA grooves, to a variety of nucleotide sequences. We find that C6, C7, and C8 diacridine are able to form 2 base pair bisintercalated complexes from either groove, whereas the C4 and C5 homologues cannot. We conclude that C6 diacridine does have the capacity to bisintercalate without violating neighbor exclusion, and that the previous proposed binding model needs revision.
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http://dx.doi.org/10.1002/bip.23409DOI Listing
April 2021

Observation and Analysis of Large Dynamic Frequency Shifts in the H NMR Signals of H-D in Deuterium-Substituted Dihydrogen Complexes.

Inorg Chem 2020 Nov 19;59(21):15570-15573. Epub 2020 Oct 19.

School of Chemistry, University of New South Wales (UNSW), Sydney, New South Wales 2052, Australia.

A dynamic frequency shift (DFS) in the H NMR resonance of the HD unit of the deuterium-labeled dihydrogen complex [Ru(D)(η-HD)(PP)][BPh] [PP = P(CHCHCHPPr)] has been observed and analyzed. To the best of our knowledge, this is the first demonstration of the DFS for a H-D pair. The observed DFS of the center line relative to the outside lines in the H-D triplet is large, up to ∼11 Hz, because of the short H-D distance encountered in dihydrogen complexes. Analysis of the DFS as a function of the temperature, combined with density-functional-theory-calculated or least-squares-fitted electric-field-gradient (EFG) parameters, suggests an H-D bond length of 0.92-0.94 Å. A DFS was also observed in -[Fe(η-HD)(H)(dppe)], suggesting the DFS will be commonplace in dihydrogen complexes if appropriate conditions are employed for its observation. Possible applications of the DFS as a probe of the bond lengths, EFGs, and molecular motion, particularly in inorganic systems, are discussed.
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http://dx.doi.org/10.1021/acs.inorgchem.0c02082DOI Listing
November 2020

Structures and dynamics of DNA complexes of the desmethyl analog of the cytotoxin MLN944: Insights into activity when a methyl isn't futile.

J Mol Recognit 2020 08 6;33(8):e2843. Epub 2020 Apr 6.

Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, UNSW Sydney, Sydney, New South Wales, Australia.

Structure activity relationships for tricyclic-carboxamide topoisomerase II poisons indicate that cytotoxicity is enhanced by the presence of methyl, and other, groups in the position peri to the carboxamide. Linked dimers of phenazine-1-carboxamides are potent cytotoxins and one phenazine dimer, MLN944 (alternatively XR5944), has been in clinical trial. MLN944 is a template inhibitor of transcription, whereas corresponding monomers are not. Nevertheless, its cytotoxic potency is also diminished by removal of its peri methyl groups. Here, we describe NMR and molecular dynamic studies of the interaction of desmethyl MLN944 with d(ATGCAT) , d(TATGCATA) , and d(TACGCGTA) to investigate the influence of the nine-methyl group on the structure of MLN944 complexes. As with MLN944, the carboxamide group hydrogen bonds to the phenazine ring nitrogen, the ligand sandwiches the central GC base pairs in the major groove, and the protonated linker amines hydrogen bond primarily to the O6 atom of the guanines. Molecular dynamics studies reveal that the linker exists in multiple conformations, none of which produce an ideal set of hydrogen bonds. In distinction, however, the carboxamide-to-phenazine ring nitrogen hydrogen bond is weaker, the overall helix winding is less and the NMR resonances are broader in the desmethyl complexes. Exchange between free and complexed DNA, quantified using two-dimensional NOESY spectra, is faster for the desmethyl MLN944 complexes than for MLN944 complexes. Overall, the data suggest that desmethyl MLN944 DNA complexes are "looser" and more unwound at the binding site, leading to faster dissociation rates, which could account for the diminished efficacy of the desmethyl analog.
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http://dx.doi.org/10.1002/jmr.2843DOI Listing
August 2020

The Mosaic of Rottlerin: The Sequel.

J Nat Prod 2019 05 24;82(5):1190-1199. Epub 2019 Apr 24.

School of Chemistry , UNSW Australia , Sydney , NSW 2052 , Australia.

Rottlerin (1) is a potent protein kinase C δ inhibitor that possesses a wide range of biological activities. However, the potential of this molecule to be developed as a drug has been restricted by its limited availability. We report herein a gram scale quantity synthesis of rottlerin in a five-step synthetic route that can be completed within 2 days. The methodology was extended by the reaction of the key aminochromene intermediate (15) with various electron-rich arenes, forming novel unsymmetrical methylene-bridged compounds. The X-ray crystal structure revealed the boomerang shape of this kind of molecule for the first time. The direct transformation of rottlerin (1) into the natural product, isorottlerin (35), was observed for the first time, and we named this transformation the "isorottlerin change". In addition, the antibacterial activities of rottlerin (1) and new rottlerin analogues 32-34 were examined against Staphylococcus aureus. The compounds showed MIC values as low as 2.0 μM, which were comparable to the clinically used antibiotic gentamicin.
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http://dx.doi.org/10.1021/acs.jnatprod.8b00917DOI Listing
May 2019

Antarctic Moss Biflavonoids Show High Antioxidant and Ultraviolet-Screening Activity.

J Nat Prod 2017 08 7;80(8):2224-2231. Epub 2017 Aug 7.

School of Chemistry, UNSW , Sydney, NSW 2052, Australia.

Ceratodon purpureus is a cosmopolitan moss that survives some of the harshest places on Earth: from frozen Antarctica to hot South Australian deserts. In a study on the survival mechanisms of the species, nine compounds were isolated from Australian and Antarctic C. purpureus. This included five biflavonoids, with complete structural elucidation of 1 and 2 reported here for the first time, as well as an additional four known phenolic compounds. Dispersion-corrected DFT calculations suggested a rotational barrier, leading to atropisomerism, resulting in the presence of diastereomers for compound 2. All isolates absorbed strongly in the ultraviolet (UV) spectrum, e.g., biflavone 1 (UV-A, 315-400 nm), which displayed the strongest radical-scavenging activity, 13% more efficient than the standard rutin; p-coumaric acid and trans-ferulic acid showed the highest UV-B (280-315 nm) absorption. The more complex and abundant 1 and 2 presumably have dual roles as both UV-screening and antioxidant compounds. They are strongly bound to Antarctic moss cell walls as well as located inside the cells of moss from both locations. The combined high stability and photoprotective abilities of these isolates may account for the known resilience of this species to UV-B radiation and its survival in some of the toughest locations in the world.
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http://dx.doi.org/10.1021/acs.jnatprod.7b00085DOI Listing
August 2017

Bridgehead isomer effects in bis(phosphido)-bridged diiron hexacarbonyl proton reduction electrocatalysts.

Dalton Trans 2017 Mar;46(10):3207-3222

School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia.

The influence of the substitution, orientation and structure of the phosphido bridges in [Fe(CO)(μ-PR)] electrocatalysts of proton reduction has been studied. The isomers e,a-[Fe(CO){μ-P(Ar)H}] (1a(Ar): Ar = Ph, 2'-methoxy-1,1'-binaphthyl (bn')), e,e-[Fe(CO){μ-P(Ar)H}] (1b(Ar): Ar = Ph, bn') were isolated from reactions of iron pentacarbonyl and the corresponding primary phosphine, syntheses that also afforded the phosphinidene-capped tri-iron clusters, [Fe(CO)(μ-CO)(μ-Pbn')] (2) and [Fe(CO)(μ-PAr)] (3(Ar), Ar = Ph, bn'). A ferrocenyl (Fc)-substituted dimer [Fe(CO){μ:μ'-1,2-(P(CHFc)CH)CH}] (4), in which the two phosphido bridges are linked by an o-xylyl group, was also prepared. The molecular structures of complexes 1a(Ph), 1b(Ph), 1b(bn'), 2 and 4 were established by X-ray crystallography. All complexes have been examined as electrocatalysts for proton reduction using p-toluene sulfonic acid in tetrahydrofuran. Cyclic voltammograms of the dimers with acid exhibit two catalysis waves for proton reduction. The first wave, which appears at the potential of the primary reduction, reaches maximum current (turnover) at moderate acid concentrations and is rapidly overtaken by the second wave, which appears at more negative potential. Both of these reductive waves show an initial first order dependence on acid. The electrochemistry and electrocatalyses of the [Fe(CO)(μ-PR)] dimers show subtle variations with the nature of the bridging phosphido group(s), including the orientation of bridgehead hydrogen atoms.
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http://dx.doi.org/10.1039/c6dt01494aDOI Listing
March 2017

Photochromic switching behaviour of donor-acceptor Stenhouse adducts in organic solvents.

Chem Commun (Camb) 2016 Nov;52(93):13576-13579

School of Chemistry, The University of New South Wales, High St, Kensington, NSW 2052, Australia.

We report photochromic donor-acceptor Stenhouse adducts (DASAs) capable of fully reversible photoisomerization with visible light in organic solvents including chloroform, acetonitrile and benzene. The rates of photoisomerization and thermal reversion can be tuned by altering the electronics of the donor adduct. X-Ray crystallography and photo-NMR experiments unambiguously establish molecular structures.
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http://dx.doi.org/10.1039/c6cc08079kDOI Listing
November 2016

Diastereoselective Synthesis and Conformational Analysis of (2R)- and (2S)-Fluorostatines: An Approach Based on Organocatalytic Fluorination of a Chiral Aldehyde.

Org Lett 2016 Feb 10;18(4):662-5. Epub 2016 Feb 10.

School of Chemistry, UNSW Australia , Sydney, NSW 2052, Australia.

Stereoselectively fluorinated analogues of the amino acid statine have been efficiently synthesized. The key step is an organocatalytic electrophilic fluorination of a chiral β-oxygenated aldehyde, which provided a test of both diastereoselectivity and chemoselectivity. The target statine analogues were found to adopt unique conformations influenced by the fluorine gauche effect, rendering them potentially valuable building blocks for incorporation into bioactive peptides.
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http://dx.doi.org/10.1021/acs.orglett.5b03592DOI Listing
February 2016

Observation of Cationic Transition Metal-Alkane Complexes with Moderate Stability in Hydrofluorocarbon Solution.

J Am Chem Soc 2016 Jan 22;138(1):281-8. Epub 2015 Dec 22.

School of Chemistry, University of New South Wales , Sydney, NSW 2052, Australia.

In seeking to create more-stable transition metal-alkane complexes, we generated cationic alkane complexes of the type [(HEB)Re(CO)2(alkane)][Al(OR(f))4] (HEB = η(6)-hexaethylbenzene; alkane = cyclopentane (16) or pentane (17-19); OR(f) = perfluoro-tert-butoxy) via photolysis of the precursor complex [(HEB)Re(CO)3][Al(OR(f))4] (15) in the presence of the added alkane. The alkane complexes were generated in a hydrofluorocarbon (HFC) solvent, most often CF3CH2CF3, which is capable of simultaneously dissolving the ionic complex 15 and a small amount of alkane at low temperature (183 K). Use of the HFC solvent in tandem with the highly fluorinated, solubilizing, weakly coordinating [Al(OR(f))4](-) anion overcomes the technical difficulty of combining ionic species with alkanes in solution without the solvent molecules rapidly displacing the bound alkane ligand, as the alkanes bind in preference to the HFCs to the organometallic fragments employed in this study. The [(HEB)Re(CO)2(alkane)](+) complexes are more long-lived than the corresponding neutral alkane complexes [(HEB)W(CO)2(alkane)] and [CpRe(CO)2(alkane)] (Cp = η(5)-cyclopentadienyl), with samples of [CpRe(CO)2(cyclopentane)] decaying significantly more rapidly than [(HEB)Re(CO)2(alkane)](+) when present in the same solution. Intramolecular exchange of the methylene group bound to the metal within the cyclopentane ligand in 16 was observed at 212 K, with the 1,2 shifts appearing to be faster than 1,3 shifts.
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http://dx.doi.org/10.1021/jacs.5b10583DOI Listing
January 2016

The Mosaic of Rottlerin.

J Org Chem 2015 Nov 14;80(21):10668-74. Epub 2015 Oct 14.

School of Chemistry, The University of New South Wales , Sydney, New South Wales 2052, Australia.

The first total synthesis of rottlerin is described. The methodology allows the development of potential novel protein kinase C δ (PKCδ) analogues for better treatment of various diseases. Kamalachalcone A and dimeric rottlerin were synthesized in a very practical and economical way using FeCl3 as a catalyst.
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http://dx.doi.org/10.1021/acs.joc.5b01827DOI Listing
November 2015

Improving Child Oral Health: Cost Analysis of a National Nursery Toothbrushing Programme.

PLoS One 2015 25;10(8):e0136211. Epub 2015 Aug 25.

Dental School, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

Unlabelled: Dental caries is one of the most common diseases of childhood. The aim of this study was to compare the cost of providing the Scotland-wide nursery toothbrushing programme with associated National Health Service (NHS) cost savings from improvements in the dental health of five-year-old children: through avoided dental extractions, fillings and potential treatments for decay.

Methods: Estimated costs of the nursery toothbrushing programme in 2011/12 were requested from all Scottish Health Boards. Unit costs of a filled, extracted and decayed primary tooth were calculated using verifiable sources of information. Total costs associated with dental treatments were estimated for the period from 1999/00 to 2009/10. These costs were based on the unit costs above and using the data of the National Dental Inspection Programme and then extrapolated to the population level. Expected cost savings were calculated for each of the subsequent years in comparison with the 2001/02 dental treatment costs. Population standardised analysis of hypothetical cohorts of 1000 children per deprivation category was performed.

Results: The estimated cost of the nursery toothbrushing programme in Scotland was £1,762,621 per year. The estimated cost of dental treatments in the baseline year 2001/02 was £8,766,297, while in 2009/10 it was £4,035,200. In 2002/03 the costs of dental treatments increased by £213,380 (2.4%). In the following years the costs decreased dramatically with the estimated annual savings ranging from £1,217,255 in 2003/04 (13.9% of costs in 2001/02) to £4,731,097 in 2009/10 (54.0%). Population standardised analysis by deprivation groups showed that the largest decrease in modelled costs was for the most deprived cohort of children.

Conclusions: The NHS costs associated with the dental treatments for five-year-old children decreased over time. In the eighth year of the toothbrushing programme the expected savings were more than two and a half times the costs of the programme implementation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136211PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549338PMC
May 2016

Bio-inspired transition metal-organic hydride conjugates for catalysis of transfer hydrogenation: experiment and theory.

Chemistry 2015 Feb 12;21(7):2821-34. Epub 2014 Dec 12.

School of Chemistry, The University of New South Wales, Sydney, NSW 2052 (Australia).

Taking inspiration from yeast alcohol dehydrogenase (yADH), a benzimidazolium (BI(+) ) organic hydride-acceptor domain has been coupled with a 1,10-phenanthroline (phen) metal-binding domain to afford a novel multifunctional ligand (L(BI+) ) with hydride-carrier capacity (L(BI+) +H(-) ⇌L(BI) H). Complexes of the type [Cp*M(L(BI) )Cl][PF6 ]2 (M=Rh, Ir) have been made and fully characterised by cyclic voltammetry, UV/Vis spectroelectrochemistry, and, for the Ir(III) congener, X-ray crystallography. [Cp*Rh(L(BI) )Cl][PF6 ]2 catalyses the transfer hydrogenation of imines by formate ion in very goods yield under conditions where the corresponding [Cp*Ir(L(BI) )Cl][PF6 ] and [Cp*M(phen)Cl][PF6 ] (M=Rh, Ir) complexes are almost inert as catalysts. Possible alternatives for the catalysis pathway are canvassed, and the free energies of intermediates and transition states determined by DFT calculations. The DFT study supports a mechanism involving formate-driven RhH formation (90 kJ mol(-1) free-energy barrier), transfer of hydride between the Rh and BI(+) centres to generate a tethered benzimidazoline (BIH) hydride donor, binding of imine substrate at Rh, back-transfer of hydride from the BIH organic hydride donor to the Rh-activated imine substrate (89 kJ mol(-1) barrier), and exergonic protonation of the metal-bound amide by formic acid with release of amine product to close the catalytic cycle. Parallels with the mechanism of biological hydride transfer in yADH are discussed.
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http://dx.doi.org/10.1002/chem.201405129DOI Listing
February 2015

The solution structure of bis(phenazine-1-carboxamide)-DNA complexes: MLN 944 binding corrected and extended.

Biopolymers 2014 Nov;101(11):1099-113

Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, UNSW Australia, Sydney, 2052, NSW, Australia.

MLN 944 is a bisintercalating DNA-binding antitumor agent known to be a template inhibitor of transcription. Previous (1) H NMR studies of its d(ATGCAT)2 complex concluded that its phenazine chromophores are protonated. However, we find that this is not so, which has important consequences for the charged state of the ligand, for the orientation of its 1-carboxamide group in the complex, and for the details of the interaction of its protonated interchromophore linker with the DNA base pairs. Here, we report a corrected solution structure of the MLN 944-d(ATGCAT)2 complex, and extend the study to complexes with d(TATGCATA)2 , and d(TACGCGTA)2 , using a variety of (1) H and (31) P NMR methods and molecular dynamics simulations employing the AMBER 12 force field. We find that for all three complexes MLN 944 binds as a dication, in which the chromophores are uncharged, in the DNA major groove spanning the central 2 GC base pairs in a manner that maintains the dyad symmetry of the DNA. The carboxamide group lies in the plane of the chromophore, its NH making hydrogen bonding interactions with the phenazine N10 nitrogen, and the protonated linkers form hydrogen bonds with the O6 atom of guanine. The dynamics simulations reveal extensive solvent interactions involving the linker amines, the carboxamide group, and the DNA bases.
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http://dx.doi.org/10.1002/bip.22513DOI Listing
November 2014

A Benchmark Ab Initio and DFT Study of the Structure and Binding of Methane in the σ-Alkane Complex CpRe(CO)2(CH4).

J Chem Theory Comput 2013 May 4;9(5):2199-208. Epub 2013 Apr 4.

School of Chemistry, University of New South Wales , NSW 2052, Australia.

Ab initio molecular orbital theory and density functional theory (DFT) procedures have been used to study the binding of methane in CpRe(CO)2(CH4), the simplest σ-alkane complex in the experimentally widely studied CpRe(CO)2(alkane) family. We find the optimal Re···C, Re···H and C···H distances to be 2.60, 1.92, and 1.15 Å, respectively, on the composite-CCSD(T)/def2-QZVPP (CCSD(T)/def2-TZVP with supplement for the larger def2-QZVPP basis set at the second-order Møller-Plesset perturbation theory level) potential energy surface which has been mapped out at this level of theory. The enthalpy of binding at 298 K was determined to be 62.0 kJ mol(-1) at the composite-CCSD(T)/CBS//B3-PW91/aug-cc-pVTZ-PP level. Benchmarks on the various DFT procedures show that some functionals give good geometries but underestimate binding energies, while others yield poor geometries but give closer agreements with the composite-CCSD(T) binding energy. On the other hand, the ωB97X-D functional gives fair agreements with composite-CCSD(T) for both geometry optimization as well as binding energy. Thus, it appears to be a reliable, easily implemented, and cost-effective means for studying Re-alkane complexes. Good binding energies are also obtained with several common functionals when D3 dispersion corrections are applied. Selected dispersion-corrected DFT methods (B3PW91-D3, TPSSh-D3, and B98-D3) were found to be quite accurate for the calculation of binding energies of several other model metal-CH4 complexes containing a range of metal centers (Rh, Pd, W, Ir, Pt). We also note that, for single-point energy calculation of the Re-CH4 binding, the PWP-B95-D3 double-hybrid DFT procedure provides an excellent agreement with the benchmark energy at only a slightly higher computational requirement.
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http://dx.doi.org/10.1021/ct400013pDOI Listing
May 2013

Stereodynamics in eight-coordination; a 2D NMR spectroscopic and computational study of the exchange process in ThCl4(Me2NCH2CH2NMe2)2.

Inorg Chem 2012 Oct 19;51(19):10141-7. Epub 2012 Sep 19.

School of Chemistry, University of New South Wales (UNSW), Sydney, New South Wales 2052, Australia.

The (13)C{(1)H} NMR spectrum of eight-coordinate ThCl(4)(tmed)(2), where tmed = Me(2)NCH(2)CH(2)NMe(2), shows that two isomers are present at 219.8 K in a ratio of ≈8:1 and inversion of the five-membered Th-tmed ring is slow at this temperature in both isomers. The 2D (13)C{(1)H} exchange spectroscopy (EXSY) spectrum shows that each of the two inequivalent methyl groups of the major isomer does not exchange directly with each other but that they both exchange with both of the two inequivalent methyl groups found in the minor isomer. This implies that interconversion of the two enantiomers of the major isomer proceeds by a stepwise process that involves the minor isomer. The interconversion of the isomers involves a ring-inversion process that may proceed with or without Th-N bond breaking, and the NMR spectra cannot distinguish between these two processes nor can density functional theory (DFT) calculations (B3PW91 and M06 with consideration of dispersion effects and solvent) because these two possibilities proceed by way of transition states of similar energies in this case.
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http://dx.doi.org/10.1021/ic300586fDOI Listing
October 2012

Observation of a tungsten alkane σ-complex showing selective binding of methyl groups using FTIR and NMR spectroscopies.

J Am Chem Soc 2012 May 23;134(20):8294-7. Epub 2012 Mar 23.

Research School of Chemistry, Australian National University, Canberra ACT, Australia.

The alkane σ-complex (HEB)W(CO)(2)(pentane) (HEB = η(6)-hexaethylbenzene) is produced from the UV photolysis of (HEB)W(CO)(3) in alkane solvents at low temperature. IR and (1)H and (13)C NMR spectroscopic data are reported, representing the first NMR data for a group 6 alkane complex. Only binding of the methyl functionality of the pentane ligand was observed in (HEB)W(CO)(2)(pentane). This contrasts with the previously reported binding of pentane to rhenium fragments, wherein both methylene and methyl groups were observed to bind, with a slight preference for binding of the former. The reason for the preference for binding through the methyl group is investigated, and the steric requirement for the pentane to adopt an unfavorable gauche conformation when bound via a methylene is identified as a contributing factor.
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http://dx.doi.org/10.1021/ja300281sDOI Listing
May 2012

Rhodium complexes of a chelating ligand with imidazol-2-ylidene and pyridin-2-ylidene donors: the effect of C-metalation of nicotinamide groups on uptake of hydride ion.

Inorg Chem 2012 Feb 6;51(4):2191-203. Epub 2012 Feb 6.

School of Chemistry, The University of New South Wales, Sydney, NSW 2052 Australia.

Rhodium complexes of the imidazolylidene (C-im) N-heterocyclic carbene (NHC) ligand, C-im-pyH(+), bearing a nicotinamide cation substituent (pyH(+)) have been targeted for ligand-centered uptake and delivery of hydride ion. This work reveals that rhodium(I) complexes such as [Rh(C-im-pyH(+))(COD)X][PF(6)] (1, a: X = Cl, b: X = I) undergo facile C-metalation of the nicotinamide ring to afford rhodium complexes of a novel chelate ligand, C,C'-im-py, with coordinated imidazolylidene (C(im)) and pyridylidene (C(py)) NHC-donors. Seven examples were characterized and include rhodium(III) monomers of the general formula [Rh(C,C'-im-py)L(x)I(2)](z+) (2: z = 1, L = H(2)O or solvent, x = 2; 3, 5, 7: z = 0, L = carboxylate, x = 1) and novel rhodium(II) dimers, the anti/syn-isomers of [Rh(2)(C,C'-im-py)(2)(μOAc)(2)I(2)] (4-anti/syn). The NMR data, backed by DFT calculations, is consistent with attribution of the C,C'-im-py ligand as a bis(carbene) donor. Single crystal X-ray diffraction studies are reported for 2, 3, 4-anti, 4-syn and 7. Consistently, within the each complex, the Rh-C(im) bond length is shorter than the Rh-C(py) bond length, which is the opposite trend to that expected based on simple electronic considerations. It is proposed that intramolecular steric interactions imposed by different rings in the rigid C,C'-im-py chelate ligand dictate the observed Rh-C(NHC) bond lengths. Attempts to add hydride to the C-metalated nicotinamide ring in 3 were unsuccessful. The redox behavior of 3 and 4 and, for comparison, an analogous bis(imidazolylidene)rhodium(III) monomer (8), were characterized by cyclic voltammetry, electron paramagnetic resonance (EPR), and UV-vis spectroelectrochemistry. In 3 and 4, the C-metalated nicotinamide ring is found to exhibit a one-electron reduction process at far lower potential (-2.34 V vs. Fc(+)/Fc in acetonitrile) than the two-electron nicotinamide cation-dihydronicotinamide couple found for the corresponding nonmetalated ring (-1.24 V). The C,C'-ligand is electrochemically silent over a large potential range (from -2.3 V to the anodic solvent limit), thus for both 3 and 4 the first reduction processes are metal-centered. For 4-anti, the cyclic voltammetry and UV-vis spectrochemical results are consistent with a diamagnetic [Rh(I)Rh(II)](2) tetrameric reduction product. Density functional theory (DFT) calculations were used to further probe the uptake of hydride ion by the nicotinamide ring, both before and after C-metalation. It is found that C-metalation significantly decreases the ability of the nicotinamide ring to take up hydride ion, which is attributed to the "carbene-like" character of a C-metalated pyridylidene ring.
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http://dx.doi.org/10.1021/ic202164vDOI Listing
February 2012

Low valent and hydride complexes of NHC coordinated gallium and indium.

Dalton Trans 2012 Jan 14;41(3):946-52. Epub 2011 Nov 14.

School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia.

The reactions of the N-heterocyclic carbene 1,3-dimesitylimidazol-2-ylidene (IMes) with Ga[GaCl(4)], "GaI", InCl(2) and GaBr(3) have been examined. All reactions using a low valent gallium or indium starting material led to species of the form [{MX(2)(IMes)}(2)], where M = Ga, X = Cl (1), I (2); M = In, X = Cl (3), with disproportionation and loss of gallium metal in the case of 2. Reaction of IMes with gallium tribromide yields the air and moisture stable complex [GaBr(3)(IMes)] (4), which has been used as a precursor to the mixed bromohydrides [GaBrH(2)(IMes)] (5) and [GaBr(2)H(IMes)] (6) by (i) ligand redistribution with [GaH(3)(IMes)], (ii) hydride-bromide exchange with triethylsilane, and (iii) alkylation with (n)butyllithium followed by β-hydride elimination (6 only). Attempts to prepare 1, or monovalent analogues such as [{GaCl(IMes)}(n)], by thermally induced reductive elimination of dihydrogen from the chlorohydride congeners of 5 and 6 resulted in isolation of the known compounds [IMesCl][Cl] (IMesCl = 1,3-dimesityl-2-chloroimidazolium), and/or 1,3-dimesityl-2-dihydroimidazole, and gallium metal. Preliminary photochemical NMR spectroscopy and catalytic studies of 5 and 6 aimed at reductive dehydrogenation under milder conditions are reported. Compounds 1 and 4 have been characterised by single crystal X-ray structure determination.
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http://dx.doi.org/10.1039/c1dt11202cDOI Listing
January 2012

Transition metal-alkane σ-complexes with oxygen donor co-ligands.

J Am Chem Soc 2011 Sep 15;133(35):13806-9. Epub 2011 Aug 15.

Institute of Advanced Studies, Australian National University, Canberra, ACT, Australia.

A new family of long-lived alkane σ-complexes of the type (L(OEt))Re(CO)(2)(alkane) [alkane = cyclopentane, cyclohexane, pentane; L(OEt) = cyclopentadienyltris(diethylphosphito)cobaltate(III)] has been observed using both IR and NMR spectroscopies and computationally interrogated with DFT methods. The oxygen-rich coordination spheres makes these complexes perhaps more relevant as models for intermediates in metal oxide mediated hydrocarbon transformations than other known alkane σ-complexes.
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http://dx.doi.org/10.1021/ja203470yDOI Listing
September 2011

Photochromic spirooxazines functionalized with oligomers: investigation of core-oligomer interactions and photomerocyanine isomer interconversion using NMR spectroscopy and DFT.

J Org Chem 2010 May;75(9):2851-60

Centre for Marine Bio-Innovation, The University of New South Wales, Sydney, NSW 2052, Australia.

Photochromic spirooxazines functionalized with poly(ethylene glycol) (PEG) and poly(dimethylsiloxane) (PDMS) oligomers were monitored using NMR spectroscopy at temperatures between 193 and 233 K before and after in situ exposure to UV irradiation. NOESY and ROESY experiments reveal the TTC (trans-s-trans-cis) isomer to be the dominant merocyanine isomer formed on photolysis, with some CTC (cis-s-trans-cis) isomer also present. Significant ROE cross peaks were observed between the "bulk" of the oligomeric units and protons across the entire photochromic core of the molecule, the intensity of these cross peaks suggesting that the interaction of the oligomer side chain and core of the molecule is significantly enhanced by the permanent attachment, especially with the PDMS side chain. The 2D NMR spectra indicate that there is exchange between the TTC and CTC isomers even at 193 K. This isomerization of the parent spirooxazine compounds, lacking the oligomeric side chains, was found to be acid-catalyzed, and DFT calculations support the strong possibility that it is the protonated merocyanine form that undergoes the facile isomerization process. Interconversion of the different merocyanine isomers is suggested to be fast on the NMR time scale under many experimental conditions, precluding the observation of different isomers using NMR spectroscopy at room temperature.
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http://dx.doi.org/10.1021/jo100081gDOI Listing
May 2010

NMR assignment of prespore specific antigen--a cell surface adhesion glycoprotein from Dictyostelium discoideum.

Biomol NMR Assign 2009 Jun 7;3(1):1-3. Epub 2008 Nov 7.

Department of Chemistry & Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia.

Presopore-specific antigen (PsA) is a cell surface glycoprotein of the cellular slime mould Dictyostelium discoidum implicated in cell adhesion. The (15)N, (13)C and (1)H chemical shift assignments of PsA were determined from multidimensional, multinuclear NMR experiments. Resonance assignments have been made for both the N-terminal globular domain and its attached O-glycosylated PTVT linker motif.
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http://dx.doi.org/10.1007/s12104-008-9126-4DOI Listing
June 2009

Fluxionality in a paramagnetic seven-coordinate iron(II) complex: a variable-temperature, two-dimensional NMR and DFT study.

Inorg Chem 2009 Jun;48(11):4863-72

School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia.

The preparation and detailed characterizations of the high-spin seven-coordinate complexes [M(kappa(7)N-L)](ClO(4))(2) (M = Mn(II), Fe(II); L = N,N,N',N'-tetrakis(2-pyridylmethyl)-2,6-bis(aminomethyl)pyridine) are described. The X-ray crystal structures reveal seven-coordinate metal complex ions. Consideration of continuous shape measures reveals that the coordination environments about the metal ions are better described as having (C(s)) face-capped trigonal prismatic symmetry than (C(2)) pentagonal bipyramidal symmetry. The (S = (5)/(2)) Mn(II) species shows complicated X-band electron paramagnetic resonance (EPR) spectra and broad, unrevealing (1)H NMR spectra. In contrast, the (S = 2) Fe(II) complex is EPR-silent and shows completely interpretable (1)H NMR spectra containing the requisite number of paramagnetically shifted peaks in the range delta +150 to -60. The (13)C NMR spectra are likewise informative. Variable-temperature (1)H NMR spectra show coalescences and decoalescences indicative of an intramolecular process that pairwise-exchanges the nonequivalent pyridylmethyl "arms" of the two bis(pyridylmethyl)amine (bpa) domains. A suite of NMR techniques, including T(1) relaxation measurements and variable-temperature (1)H-(1)H correlation spectroscopy, (1)H-(1)H total correlation spectroscopy, (1)H-(1)H nuclear Overhauser effect spectroscopy/exchange spectroscopy, and (1)H-(13)C heteronuclear multiple-quantum coherence experiments, has been used to assign the NMR spectra and characterize the exchange process. Analysis of the data from these experiments yields the following thermodynamic parameters for the exchange: DeltaH++ = 53.6 +/- 2.8 kJ mol(-1), DeltaS++ = -10.0 +/- 9.8 J K(-1) mol(-1), and DeltaG++ (298 K) = 50.6 kJ mol(-1). Density functional theory (B3LYP) calculations have been used to explore the energetics of possible mechanistic pathways for the underlying fluxional process. The most plausible mechanism found involves dissociation of a pyridylmethyl arm to afford a strained six-coordinate species followed by rebinding of the arm in a different position to afford a new seven-coordinate transition state in which the pyridylmethyl arms within each bpa domain are essentially equivalent; the calculated energy barrier for this process is 53.5 kJ mol(-1), in good agreement with the observations.
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http://dx.doi.org/10.1021/ic900233dDOI Listing
June 2009

A mild and general method for the synthesis of 5-substituted and 5,5-disubstituted fulleroprolines.

Org Lett 2008 Mar 21;10(6):1315-7. Epub 2008 Feb 21.

School of Chemistry, University of Wollongong, Wollongong, New South Wales, 2522, Australia.

The reductive ring-opening of fullerenyldihydropyrrole yields ethyl N-benzhydryl fullerenyl[60]glycinate, which is deprotected to give ethyl fullerenylglycinate. The free amine is able to react with a variety of aldehydes and ketones in a Mannich-type process to produce 5-substituted and 5,5-disubstituted fulleroprolines and represents a versatile and general strategy to this class of compounds.
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http://dx.doi.org/10.1021/ol8002157DOI Listing
March 2008

Roles of alpha and beta carbonic anhydrases of Helicobacter pylori in the urease-dependent response to acidity and in colonization of the murine gastric mucosa.

Infect Immun 2008 Feb 19;76(2):497-509. Epub 2007 Nov 19.

Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France.

Carbon dioxide occupies a central position in the physiology of Helicobacter pylori owing to its capnophilic nature, the large amounts of carbon dioxide produced by urease-mediated urea hydrolysis, and the constant bicarbonate supply in the stomach. Carbonic anhydrases (CA) catalyze the interconversion of carbon dioxide and bicarbonate and are involved in functions such as CO(2) transport or trapping and pH homeostasis. H. pylori encodes a periplasmic alpha-CA (alpha-CA-HP) and a cytoplasmic beta-CA (beta-CA-HP). Single CA inactivation and double CA inactivation were obtained for five genetic backgrounds, indicating that H. pylori CA are not essential for growth in vitro. Bicarbonate-carbon dioxide exchange rates were measured by nuclear magnetic resonance spectroscopy using lysates of parental strains and CA mutants. Only the mutants defective in the alpha-CA-HP enzyme showed strongly reduced exchange rates. In H. pylori, urease activity is essential for acid resistance in the gastric environment. Urease activity measured using crude cell extracts was not modified by the absence of CA. With intact CA mutant cells incubated in acidic conditions (pH 2.2) in the presence of urea there was a delay in the increase in the pH of the incubation medium, a phenotype most pronounced in the absence of H. pylori alpha-CA. This correlated with a delay in acid activation of the urease as measured by slower ammonia production in whole cells. The role of CA in vivo was examined using the mouse model of infection with two mouse-adapted H. pylori strains, SS1 and X47-2AL. Compared to colonization by the wild-type strain, colonization by X47-2AL single and double CA mutants was strongly reduced. Colonization by SS1 CA mutants was not significantly different from colonization by wild-type strain SS1. However, when mice were infected by SS1 Delta(beta-CA-HP) or by a SS1 double CA mutant, the inflammation scores of the mouse gastric mucosa were strongly reduced. In conclusion, CA contribute to the urease-dependent response to acidity of H. pylori and are required for high-grade inflammation and efficient colonization by some strains.
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http://dx.doi.org/10.1128/IAI.00993-07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223474PMC
February 2008

Modulation of brain metabolism by very low concentrations of the commonly used drug delivery vehicle dimethyl sulfoxide (DMSO).

J Neurosci Res 2008 Jan;86(1):208-14

Prince of Wales Medical Research Institute, Randwick, Australia.

Dimethyl sulfoxide (DMSO) has long been used in studies as a vehicle to enhance the solubility and transport of ligands in biological systems. The effects of this drug on the outcomes of such studies are still unclear, with concentrations of DMSO reported as "safe" varying considerably. In the present work, we investigated the effects of very low concentrations of DMSO on the brain metabolism of [3-(13)C]pyruvate and D-[1-(13)C]glucose using (1)H/(13)C NMR spectroscopy and a guinea pig cortical brain slice model. Our results show that DMSO is accumulated by brain slices. DMSO at all concentrations [0.000025%-0.25% (v/v)] increased the metabolic rate when [3-(13)C]pyruvate was used as a substrate and also in the presence of D-[1-(13)C]glucose (0.00025%-0.1% DMSO). These results are consistent with DMSO stimulating respiration, which it may do through altering the kinetics of ATP-requiring reactions. Our results also emphasize that there is no practical concentration of DMSO that can be used in metabolic experiments without effect. Therefore, care should be taken when evaluating the actions of drugs administered in combination with DMSO.
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http://dx.doi.org/10.1002/jnr.21477DOI Listing
January 2008

A delicate balance of complexation vs. activation of alkanes interacting with [Re(Cp)(CO)(PF3)] studied with NMR and time-resolved IR spectroscopy.

Proc Natl Acad Sci U S A 2007 Apr 13;104(17):6927-32. Epub 2007 Apr 13.

School of Chemistry, University of New South Wales, Sydney 2052, Australia.

The organometallic alkane complexes Re(Cp)(CO)(PF(3))(alkane) and Re(Cp)(CO)(2)(alkane) have been detected after the photolysis of Re(Cp)(CO)(2)(PF(3)) in alkane solvent. NMR and time-resolved IR experiments reveal that the species produced by the interaction of n-pentane with [Re(Cp)(CO)(PF(3))] are an equilibrium mixture of Re(Cp)(CO)(PF(3))(pentane) and Re(Cp)(CO)(PF(3))(pentyl)H. The interaction of cyclopentane with [Re(Cp)(CO)(PF(3))] most likely results in a similar equilibrium between cyclopentyl hydride and cyclopentane complexes. An increasing proportion of alkane complex is observed on going from n-pentane to cyclopentane to cyclohexane, where only a small amount, if any, of the cyclohexyl hydride form is present. In general, when [Re(Cp)(CO)(PF(3))] reacts with alkanes, the products display a higher degree of oxidative cleavage in comparison with [Re(Cp)(CO)(2)], which favors alkane complexation without activation. Species with the formula Re(Cp)(CO)(PF(3))(alkane) have higher thermal stability and lower reactivity toward CO than the analogous Re(Cp)(CO)(2)(alkane) complexes.
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http://dx.doi.org/10.1073/pnas.0610212104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855363PMC
April 2007

Structural reassignment of the mono- and bis-addition products from the addition reactions of N-(Diphenylmethylene)glycinate esters to [60]fullerene under Bingel conditions.

J Org Chem 2005 Oct;70(21):8572-4

NMR Facility, School of Chemistry, University of New South Wales, Sydney, New South Wales 2052, Australia.

The addition of N-(diphenylmethylene)glycinate esters (Ph2C=NCH2CO2R) to [60]fullerene under Bingel conditions gives [60]fullerenyldihydropyrroles and not methano[60]fullerenyl iminoesters [C60C(CO2R)(N=CPh2)] as previously reported. Unequivocal evidence for the structure of C60C(CO2Et)(N=CPh2) was provided by INADEQUATE NMR studies on 13C enriched material. New mechanistic details are proposed to account for the formation of [60]fullerenyldihydropyrroles and their reductive ring-opening reactions.
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http://dx.doi.org/10.1021/jo051282uDOI Listing
October 2005
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