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Biomedical subjects

Robert McDonald

Publications and source records attributed to Robert McDonald.

At least 37 records · Page 2Linked to original sources
PubMed2005

Brønsted acid-catalyzed allylboration: short and stereodivergent synthesis of all four eupomatilone diastereomers with crystallographic assignments.

This study describes a novel Brønsted acid-catalyzed allylboration method suitable for the most difficult, electronically deactivated allylboronate and aldehyde substrates. This method circumvents the use of metal ions, and rather employs a simple and cheap catalyst, triflic acid. Its usefulness as a complementary allylboration variant was demonstrated with a four-step, stereodivergent synthesis of all four diastereomers of eupomatilone-6 from a single allylboronate. A thorough proof of stereochemistry supported by as many as five X-ray crystallographic structures brings an end to the ambiguity of the original stereochemical assignments. Further to the TfOH-catalyzed allylboration, the synthetic route featured a number of remarkable observations: the surprising reactivity of 2-bromo-3,4,5-trimethoxybenzaldehyde, the subtle reagent control observed in the hydrogenation of an alpha-exo-methylene lactone intermediate, and the success of a difficult case of Suzuki biaryl coupling using Buchwald's conditions.

Acids↗
PubMed2005

New bidentate cationic and zwitterionic relatives of Crabtree's hydrogenation catalyst.

Inspired by the monodentate P,N ligation strategy featured in Crabtree's catalyst [(COD)Ir(PCy3)(Py)]+PF6-([1]+PF6-), a new class of bidentate cationic ([2]+X-) and zwitterionic (3) Ir complexes have been developed, which are capable of mediating the hydrogenation of alkenes under mild conditions and in a wider range of solvents than is possible for [1]+PF6-.

Journal Article↗
PubMed2005

Synthesis and coordination chemistry of a photoswitchable bis(phosphine) ligand.

A 1,2-dithienylethene compound bearing bis(phosphine) groups (1o) represents a new class of photoresponsive ligands where there are steric and electronic differences between two photogenerated isomers. The coordination chemistry of this ligand class is demonstrated by preparing a gold(I) complex (2o) and a phosphine selenide (3o).

Journal Article↗
PubMed2005

Synthesis of cyclo-2,4,6-triarsa-1,3,5-triazanes from cyclo-2,4-diarsa-1,3-diazanes demonstrating the general influence of substituent steric strain on the relative stability of pnictazane oligomers.

2,4-Dichloro-1,3-diaryl-cyclo-2,4-diarsa-1,3-diazanes (aryl = 2,6-dimethylphenyl, Dmp, or 2,6-diisopropylphenyl, Dipp) have been transformed into the corresponding 2,4,6-trichloro-cyclo-2,4,6-triarsa-1,3,5-triazanes on reaction with GaCl(3) followed by 4-(dimethylamino)pyridine (DMAP). The nitrogen bound Dmp and Dipp substituents impose "medium" substituent steric strain on the heterocycles influencing the relative thermodynamic stability of potential oligomers in favor of the trimers. This ring expansion disproportionation reaction is initiated by chloride ion abstraction, and the intermediate 2,4-dichloro-1,3,5-tris(2,6-diisopropylphenyl)-cyclo-2,4-diarsa-1,3,5-triazane-6-arsenium tetrachlorogallate has been isolated and structurally characterized. Subsequent reaction with 4-(dimethylamino)pyridine (DMAP) effects release of chloride ion from the gallate anion and consequential formation of a covalent As-Cl bond in the trimer. The observations are analogous to those for the phosphorus derivatives demonstrating a general applicability of this new synthetic procedure for the development and diversification of cyclopnictazane chemistry.

Journal Article↗
PubMed2005

Esters of 2-iodoxybenzoic acid: hypervalent iodine oxidizing reagents with a pseudobenziodoxole structure.

Esters of 2-iodoxybenzoic acid (IBX-esters) were prepared by the hypochlorite oxidation of the corresponding 2-iodobenzoate esters and isolated as chemically stable, microcrystalline products. These hypervalent iodine compounds are potentially valuable oxidizing reagents belonging to a new class of pentavalent iodine compounds with a pseudobenziodoxole structure. Methyl 2-iodoxybenzoate can be further converted to the diacetate or a bis(trifluoroacetate) derivative by treatment with acetic anhydride or trifluoroacetic anhydride, respectively. Single-crystal X-ray diffraction analysis of methyl 2-[(diacetoxy)iodosyl]benzoate 8a reveals a pseudobenziodoxole structure with three relatively weak intramolecular I...O interactions. The dimethyl and diisopropyl esters of 2-iodoxyisophthalic acid were prepared by oxidation of the respective iodoarenes with dimethyldioxirane. Single-crystal X-ray diffraction analysis of diisopropyl 2-iodoxyisophthalate 6b showed intramolecular I...O interaction with the carbonyl oxygen of only one of the two carboxylic groups, while NMR spectra in solution indicated equivalency of both ester groups. IBX-esters, methyl 2-[(diacetoxy)iodosyl]benzoate, and 2-iodoxyisophthalate esters can oxidize alcohols to the respective aldehydes or ketones in the presence of trifluoroacetic acid or boron trifluoride etherate. The bis(trifluoroacetate) derivative can oxidize alcohols to carbonyl compounds without acid catalyst.

Alcohols↗
PubMed2005

7:8,9:10-dibenzo-1,2,3,4-tetrafluoro- triphenylene: synthesis, structure, and photophysical properties of a novel [5]helicene.

A simple and efficient synthesis and crystallographic analysis of the partially fluorinated 7:8,9:10-dibenzo-1,2,3,4-tetrafluorotriphenylene, 1, in 59% yield is reported. Compound 1 is a blue luminescent [5]helicene in both solution and the solid state. It spontaneously forms enantiomorphous single crystals from racemic samples and exhibits slipped, face-to-face F...C(pi) contacts within the stacks of molecules.

Crystallography, X-Ray↗
PubMed2005

Chelate and pincer carbene complexes of rhodium and platinum derived from hexaphenylcarbodiphosphorane, Ph3P=C=PPh3.

The reaction of [(cod)RhCl]2 with Ph3P=C=PPh3 (1) gave the bidentate Rh(I) carbene complex, (cod)Rh[eta2-C{P(C6H4)Ph2}{PPh3}] (2), in which one of the Ph groups in 1 underwent orthometalation to form the chelate. Displacement of cod by 2 equiv of PMe3 transformed 2, via a second orthometalation event, into the Rh(III) C,C,C pincer carbene complex, HRh(PMe3)2[eta3-C{P(C6H4)Ph2}2] (3). The reaction of [Me2Pt(SMe2)]2 with 1 led directly to the analogous C,C,C pincer carbene complex of Pt(II), (Me2S)Pt[eta3-C{P(C6H4)Ph2}2] (4). DFT calculations on a model form of 3 suggest a net single sigma-bonding interaction between Rh and an sp2-hybridized carbene center, with a HOMO that is predominantly carbene pz in character.

Journal Article↗
PubMed2005

Synthesis and biological evaluation of 3,4-diphenyl-1,2,5-oxadiazole-2-oxides and 3,4-diphenyl-1,2,5-oxadiazoles as potential hybrid COX-2 inhibitor/nitric oxide donor agents.

A group of 3,4-diphenyl-1,2,5-oxadiazole-2-oxides (3,4-diphenylfuroxans) and the corresponding N-desoxy 3,4-diphenyl-1,2,5-oxadiazoles (3,4-diphenylfurazans) analogs, were synthesized for in vitro evaluation as hybrid cyclooxygenase (COX) inhibitor/nitric oxide donor agents. Reaction of 1-[4-(methylsulfonyl)phenyl]-2-phenylethene with an aqueous sodium nitrite solution in acetic acid afforded a mixture (3:1 ratio) of the inseparable 4-[4-(methylsulfonyl)phenyl]-3-phenyl-1,2,5-oxadiazole-2-oxide (13a) and 3-[4-(methylsulfonyl)phenyl]-4-phenyl-1,2,5-oxadiazole-2-oxide (13b) regioisomers. A group of related regioisomers possessing either a p-aminosulfonylphenyl (16) or a p-azidosulfonylphenyl (17), moiety were obtained by chlorosulfonation of the unsubstituted 3,4-diphenylfuroxan (10) and subsequent reaction with either ammonium hydroxide or sodium azide, respectively. The methanesulfonyl regioisomers 13a,b [COX-1 IC50=11.6 microM; COX-2 IC50=0.12 microM; COX-2 selectivity index (SI)=97] and aminosulfonyl regioisomers 16 (COX-1 IC50=9.8 microM; COX-2 IC50=0.78 microM; COX-2 SI=12), like the reference drug celecoxib (COX-1 IC50=33.1 microM; COX-2 IC50=0.07 microM; COX-2 SI=472), were potent in vitro COX-2 inhibitors with a good COX-2 selectivity index. Release of nitric oxide (NO) from the 3,4-diphenylfuroxan compounds (10, 13a,b, 16, 17) was thiol-dependent since the % NO released was higher upon incubation in the presence of l-cysteine (0.57-3.18%) compared to that in phosphate buffer solution at pH7.4 (0.06-0.15%). Molecular modeling (docking) studies show that the methanesulfonyl (MeSO2) COX-2 pharmacophore present in regioisomers 13a,b is positioned in the vicinity of the COX-2 secondary pocket. The in vitro NO release data, COX-1/COX-2 inhibition and COX-2 SI structure-activity relationships acquired, and molecular modeling docking studies suggest that the 1,2,5-oxadiazole-2-oxide (furoxan) ring possesses beneficial features that should be present in a suitable central ring template (bioisostere) pertinent to the design novel hybrid COX-2 inhibitor/nitric oxide donor agents with a low ulcerogenicity profile that may be free from adverse cardiovascular effects.

Animals↗
PubMed2005

Hypervalent, low-coordinate phosphorus(III) centers in complexes of the phosphadiazonium cation with chelate ligands.

Trifluoromethylsulfonyloxy-(2,4,6-tri-tert-butylphenylimino)phosphine, Mes*NPOTf (Mes = 2,4,6-tri-tert-butylphenyl, OTf = trifluoromethanesulfonate, triflate) reacts quantitatively with the multifunctional ligands 2,2'-bipyridine (2,2'-BIPY), N,N,N',N'-tetramethylethylenediamine (TMEDA), 1,2-bis(diethylphosphino)ethane (DEPE), 1,2-bis(diphenylphosphino)ethane (DIPHOS), and N,N,N',N' ',N' '-pentamethyldiethylenetriamine (PMDETA) to give the Lewis acid-base complexes [Mes*NP(2,2'-BIPY)][OTf], [Mes*NP(TMEDA)][OTf], [Mes*NP(DIPHOS)][OTf], [Mes*NP(DEPE)][OTf], and [Mes*NP(PMDETA)][OTf], respectively. Single-crystal X-ray diffraction studies indicate that the closest contact of the ligand donor atoms occurs at phosphorus in all cases, affecting significant displacement of the OTf anion. The resulting cations [Mes*NP(L)]+ are best described as complexes of a neutral chelating ligand on a phosphadiazonium Lewis acceptor, and highlight the potential for electron-rich centers to behave as Lewis acids despite the presence of a lone pair of electrons at the acceptor site. More importantly, the new complexes represent rare examples of systems containing hypervalent, low-coordinate phosphorus(III) centers.

Journal Article↗
PubMed2005

Polyynes as a model for carbyne: synthesis, physical properties, and nonlinear optical response.

With the Fritsch-Buttenberg-Wiechell rearrangement as a primary synthetic route, a series of conjugated, triisopropylsilyl end-capped polyynes containing 2-10 acetylene units has been assembled. In a few steps, significant quantities of the polyynes are made available, which allow for a thorough analysis of their structural, physical, and optical properties. Molecules in the series have been characterized in detail using (13)C NMR spectroscopy, differential scanning calorimetry, mass spectrometry, and, for four derivatives including octayne 6, X-ray crystallography. UV-vis spectroscopy of the polyynes 1-7 shows a consistent lowering of the HOMO-LUMO gap (E(g)) as a function of the number of acetylene units (n), fitting a power-law relationship of E(g) approximately n(-)(0.379)(+/-)(0.002). The third-order nonlinear optical (NLO) properties of the polyyne series have been examined, and the nonresonant molecular second hyperpolarizabilities (gamma) increase as a function of length according to the power-law gamma approximately n(4.28)(+/-)(0.13). This result exhibits an exponent that is larger than theoretically predicted for polyynes and higher than is observed for polyenes and polyenynes. The combined linear and nonlinear optical results confirm recent theoretical studies that suggest polyynes as model 1-D conjugated systems. On the basis of UV-vis spectroscopic analysis, the effective conjugation length for this series of polyynes is estimated to be ca. n = 32, providing insight into characteristics of carbyne.

Journal Article↗
PubMed2005

Synthesis, structure, and nonlinear optical properties of diarylpolyynes.

A series of alpha,omega-diarylpolyynes has been synthesized. In addition to the synthesis of three hexaynes (3a-c), a notably improved synthesis of 1,16-diphenylhexadecaoctayne (5) is described. The third-order nonlinear optical characteristics for these molecules have been studied and show a substantial increase in molecular hyperpolarizability (gamma) as a function of increasing length. The unusual solid-state structures of compounds 3a and 3b are reported.

Journal Article↗
PubMed2005

Use of the Jones Criteria in the diagnosis of acute rheumatic fever in an Australian rural setting.

OBJECTIVE: To answer the question, are the Jones Criteria being used appropriately in the diagnosis of acute rheumatic fever (ARF) by non-specialist medical staff in a remote Australian setting? METHODS: The medical records of all patients discharged from Katherine Hospital (Northern Territory) with a diagnosis of ARF between January 2000 and April 2004 were retrospectively reviewed for adherence to the Jones Criteria. Data were also collected on specialist follow-up and need for transfer to a tertiary hospital. RESULTS: Twenty-five patients had a diagnosis of ARF and all were Aboriginal or Torres Strait Islander. Thirty-two per cent did not fulfil the Jones Criteria and of these 63% were recurrent cases. Eighty-eight per cent received specialist follow-up and of those who did not fulfil the Jones Criteria, all were diagnosed as ARF by the specialist. Only 20% required transfer to a tertiary hospital for higher-level care. CONCLUSION: The Jones Criteria are being used appropriately to diagnose initial episodes of ARF but less successfully in recurrent episodes. Specialist follow-up is essential but acute episodes can be managed in remote settings, reducing the need to transfer patients to tertiary care with resultant patient dislocation and social isolation. IMPLICATIONS: The diagnosis of ARF results in long-term penicillin prophylaxis. This is a major public health undertaking that requires correct diagnosis. This study demonstrates that the Jones Criteria are being used appropriately to diagnose ARF in a remote setting. The ability to diagnose and treat Indigenous patients within their local region reduces social isolation and creates a more positive health care experience.

Acute Disease↗