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Open Access
Abstract: Organo-osmium(II) 16-electron complexes [OsII(η6-arene)(R-PhDPEN)] (where η6-arene = para-cymene or biphenyl) can catalyze the reduction of prochiral ketones to optically pure alcohols in the presence of a hydride source. Such complexes can achieve the conversion of pyruvate to unnatural d-lactate in cancer cells. To improve the catalytic performance of these osmium complexes, we have introduced electron-donor and electron-acceptor substituents (R) into the para (R1) or meta (R2) positions of the chiral R-phenyl-sulfonyl-diphenylethylenediamine (R-PhDPEN) ligands and explored the reduction of quinones, potential biological substrates, which play a major role in cellular electron transfer chains. We show that the series of [OsII(η6-arene)(R-PhDPEN)] derivatives exhibit high turnover frequencies, enantioselectivities (>92%), and conversions (>93%) for the asymmetric transfer hydrogenation (ATH) of acetophenone-derived substrates and reduce duroquinone and menadione to their di-alcohol derivatives. Modeling of the catalysis using density functional theory (DFT) calculations suggests a mechanism involving formic acid deprotonation assisted by the catalyst amine groups, phenyl-duroquinone stacking, hydride transfer to OsII, possible CO2 coordination, and tilting of the η6-arene ring, followed by hydride transfer to the quinone. These findings not only reveal subtle differences between Ru(II) and Os(II) catalysts, but also introduce potential biological applications.
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Aug 2021
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B18-Core EXAFS
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Diamond Proposal Number(s):
[22432]
Open Access
Abstract: We have combined Cu K-edge X-ray absorption spectroscopy with NMR spectroscopy (1H and 31P) to study the Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction under operando conditions. A variety of novel, well-defined CuI iminophosphorane complexes were prepared. These ligands, based on the in situ Staudinger reduction when [Cu(PPh3)3Br] is employed, were found to be active catalysts in the CuAAC reaction. Here, we highlight recent advances in mechanistic understanding of the CuAAC reaction using spectroscopic and kinetic investigations under strict air-free and operando conditions. A mononuclear Cu triazolide intermediate is identified to be the resting state during catalysis; cyclization and protonation both have an effect on the rate of the reaction. A key finding of this study includes a novel group of highly modular CuI complexes that are active in the base-free CuAAC reaction.
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Sep 2020
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I03-Macromolecular Crystallography
I04-Macromolecular Crystallography
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Storm
Hassell-Hart
,
Andrew
Runcie
,
Tobias
Krojer
,
Jordan
Doyle
,
Ella
Lineham
,
Cory A.
Ocasio
,
Brenno A. D.
Neto
,
Oleg
Fedorov
,
Graham
Marsh
,
Hannah
Maple
,
Robert
Felix
,
Rebecca
Banks
,
Alessio
Ciulli
,
Sarah
Picaud
,
Panagis
Filippakopoulos
,
Frank
Von Delft
,
Paul
Brennan
,
Helen J. S.
Stewart
,
Timothy J.
Chevassut
,
Martin
Walker
,
Carol
Austin
,
Simon
Morley
,
John
Spencer
Diamond Proposal Number(s):
[19301]
Abstract: (+)-JD1, a rationally designed ferrocene analogue of the BET bromodomain (BRD) probe molecule (+)-JQ1, has been synthesized and evaluated in biophysical, cell-based assays as well as in pharmacokinetic studies. It displays nanomolar activity against BRD isoforms, and its cocrystal structure was determined in complex with the first bromodomain of BRD4 and compared with that of (+)-JQ1, a known BRD4 small-molecule probe. At 1 μM concentration, (+)-JD1 was able to inhibit c-Myc, a key driver in cancer and an indirect target of BRD4.
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Dec 2019
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Abstract: Classic (dynamic exchange line-shape analysis) and novel (SSTD NMR) NMR techniques have been applied in order to obtain the kinetic and thermodynamic parameters of the three main processes occurring in the fluxional behavior of Pt-allene complexes with N-containing ligands, in four and five coordination mode, in solution. Our results show intramolecular helical and rotational movements closely related to each other, confirming η1-staggered structures as possible intermediates. The ligand exchange in these complexes seems to occur via a ligand-independent dissociative mechanism, where coordinating solvents might be involved in the stabilization of the intermediates. The differences observed in the interaction of allenes with other metals could be the basis to explain the divergent reactivity observed in platinum-catalyzed processes.
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Dec 2016
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Diamond Proposal Number(s):
[11238]
Abstract: The reactivity of the Ti═Ti double bond in (μ,η5:η5-Pn†)2Ti2 (1; Pn† = 1,4-{SiiPr3}2C8H4) toward isocyanide and heteroallene substrates, and molecules featuring homonuclear bonds between main-group elements (E–E) has been explored. Reaction of 1 with methyl isocyanide or 1,3-N,N′-di-p-tolylcarbodiimide resulted in the formation of the 1:1 adducts (μ,η5:η5-Pn†)2Ti2(μ,η2-CNMe) (2) and (μ,η5:η5-Pn†)2Ti2(μ-C{N(4-C6H4CH3)}2) (3), respectively, which are thermally stable up to 100 °C in contrast to the analogous adducts formed with CO and CO2. Reaction of 1 with phenyl isocyanate afforded a paramagnetic complex, [(η8-Pn†)Ti]2(μ,κ2:κ2-O2CNPh) (4), in which the “double-sandwich” architecture of 1 has been broken and an unusual phenyl-carbonimidate ligand bridges two formally Ti(III) centers. Reaction of 1 with diphenyl dichalcogenides, Ph2E2 (E = S, Se, Te), led to the series of Ti–Ti single-bonded complexes (μ,η5:η5-Pn†)2[Ti(EPh)]2 (E = S (5), Se (6), Te (7)), which can be considered the result of a 2e– redox reaction or a 1,2-addition across the Ti═Ti bond. Treatment of 1 with azobenzene or phenyl azide afforded [(η8-Pn†)Ti]2(μ-NPh)2 (8), a bridging imido complex in which the pentalene ligands bind in an η8 fashion to each formally Ti(IV) center, as the result of a 4e– redox reaction driven by the oxidative cleavage of the Ti═Ti double bond. The new complexes 2–8 were extensively characterized by various techniques including multinuclear NMR spectroscopy and single-crystal X-ray diffraction, and the experimental work was complemented by density functional theory (DFT) studies.
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Dec 2016
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I19-Small Molecule Single Crystal Diffraction
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Oday A.
Al-owaedi
,
David C.
Milan
,
Marie-christine
Oerthel
,
Sören
Bock
,
Dmitry S.
Yufit
,
Judith A. K.
Howard
,
Simon J.
Higgins
,
Richard J.
Nichols
,
Colin J.
Lambert
,
Martin R.
Bryce
,
Paul J.
Low
Diamond Proposal Number(s):
[6749]
Open Access
Abstract: The single-molecule conductance of metal complexes of the general forms trans-Ru(C≡CArC≡CY)2(dppe)2 and trans-Pt(C≡CArC≡CY)2(PPh3)2 (Ar = 1,4-C6H2-2,5-(OC6H13)2; Y = 4-C5H4N, 4-C6H4SMe) have been determined using the STM I(s) technique. The complexes display high conductance (Y = 4-C5H4N, M = Ru (0.4 ± 0.18 nS), Pt (0.8 ± 0.5 nS); Y = 4-C6H5SMe, M = Ru (1.4 ± 0.4 nS), Pt (1.8 ± 0.6 nS)) for molecular structures of ca. 3 nm in length, which has been attributed to transport processes arising from tunneling through the tails of LUMO states.
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Sep 2016
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[6749]
Abstract: The Pd(PPh3)4/CuI-cocatalyzed reaction of
Ru(CñMCCñMCH)(PPh3)2Cp (2) with aryl iodides, Ar-I (3,
Ar = C6H4CN-4 (a); C6H4Me-4 (b); C6H4OMe-4 (c); 2,3-
dihydrobenzo[b]thiophene (d); C5H4N (e)) proceeds
smoothly in diisopropylamine and under an inert atmosphere
to give the substituted buta-1,3-diynyl complexes Ru(CñM
CCñMCAr)(PPh3)2Cp (4a-e) in moderate to good yield. The
procedure allows the rapid preparation of a range of metal
complexes of arylbuta-1,3-diynyl ligands without necessitating
the prior synthesis of the individual buta-1,3-diynes as ligand
precursors. Similar reaction of 2 with half an equivalent of 1,4-
diiodobenzene affords the bimetallic derivative {Ru-
(PPh3)2Cp}2(Ê-CñMCCñMC-1,4-C6H4−CñMCCñMC) (5). In
the presence of atmospheric oxygen, homocoupling of the diynyl reagent 2 takes place to provide the octa-1,3,5,7-tetrayndiyl
complex {Ru(PPh3)2Cp}2(Ê-CñMCCñMCCñMCCñMC) (6). Crystallographically determined molecular structures are reported
for five complexes (4a, 4b, 4d, 5, and 6). Quantum chemical calculations indicate that the HOMOs are mainly located on the
C4−C6H4−C4 and C8 bridges for 5 and 6, respectively, while spectroelectrochemical (UV−vis−NIR and IR) studies on 6
establish that oxidation takes place at the C8 bridge, likely followed by cyclodimerization reactions of the bridging ligand.
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Jun 2015
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Abstract: Polypyridyl ruthenium complexes have been
intensively studied and possess photophysical properties that
are both interesting and useful. They can act as probes for
DNA, with a substantial enhancement in emission when
bound, and can induce DNA damage upon photoirradiation.
Therefore, the synthesis and characterization of DNA binding
of new complexes is an area of intense research activity. While
knowledge of how the binding of derivatives compares to that
of the parent compound is highly desirable, this information
can be difficult to obtain. Here we report the synthesis of three
new methylated complexes, [Ru(TAP)2(dppz-10-Me)]Cl2,
[Ru(TAP)2(dppz-10,12-Me2)]Cl2, and [Ru(TAP)2(dppz-11-
Me)]Cl2 (TAP = 1,4,5,8-tetraazaphenanthrene; dppz =
dipyrido[3,2-a:2′,3′-c]phenazine), and examine the consequences for DNA binding through the use of atomic-resolution Xray
crystallography. We find that the methyl groups are located in discrete positions with a complete directional preference. This
may help to explain the quenching behavior found in solution for analogous [Ru(phen)2(dppz)]2+ derivatives.
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Jun 2015
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I19-Small Molecule Single Crystal Diffraction
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Abstract: The six-membered-ring NHC complexes Rh(6-NHC)(PPh3)2H (6-NHC = 6-iPr (1), 6-Et (2), 6-Me (3)) have been employed in the catalytic hydrodefluorination (HDF) of C6F5CF3 and 2-C6F4HCF3. Stoichiometric studies showed that 1 reacted with C6F5CF3 at room temperature to afford cis- and trans-phosphine isomers of Rh(6-iPr)(PPh3)2F (4), which re-form 1 upon heating with Et3SiH. Although up to three consecutive HDF steps prove possible with C6F5CF3, the ultimate effectiveness of the catalysts is limited by their propensity to undergo CH activation of partially fluorinated toluenes to give, for example, Rh(6-iPr)(PPh3)2(C6F4CF3) (7), which was isolated and structurally characterized.
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Nov 2014
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[6749]
Abstract: Bipyridyl appended ruthenium alkynyl complexes have been used to prepare a range of binuclear homometallic ruthenium and heterometallic ruthenium–rhenium complexes. The two metal centers are only weakly coupled, as evinced by IR and UV–vis–near NIR spectroelectrochemical experiments and supported by quantum chemical calculations. The alkynyl complexes of the type [Ru(C≡Cbpy){Ln}] ({Ln} = {(PPh3)2Cp}, {(dppe)Cp*}, {Cl(dppm)2}) undergo reversible one-electron oxidations centered largely on the alkynyl ligands, as has been observed previously for closely related complexes. The homometallic binuclear complexes, exemplified by [Ru(C2bpy-κ2-N′N-RuClCp)(PPh3)2Cp] undergo two essentially reversible oxidations, the first centered on the (C2bpy-κ2-N′N-RuClCp) moiety and the second on the Ru(C≡Cbpy)(PPh3)2Cp fragment, leading to radical cations that can be described as Class II mixed-valence complexes. The heterometallic binuclear complexes [Ru(C2bpy-κ2-N′N-ReCl(CO)3){Ln}] display similar behavior, with initial oxidation on the ruthenium fragment giving rise to a new optical absorption band with Re → Ru(C≡Cbpy) charge transfer character. The heterometallic complexes also exhibit irreversible reductions associated with the Re hetereocycle moiety.
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Aug 2014
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