33 research outputs found
Heteroaryl carbene complexes : synthesis, reactivity and redox behaviour
A series of Fischer mono- and biscarbene complexes of the type [MLn{C=(XR)R'}] was
synthesized and characterized. The redox behavior of the complexes was studied by different
techniques, including cyclic voltammetry, spectroelectrochemistry, ESR and computational
methods. Different transition metals (M) and carbene substituents (XR, R') were employed to
compare both the effect of the central metal atom as well as the carbene substituent.
Thienyl, furyl and ferrocenyl chromium(0) mono- and biscarbene complexes with ethoxy and
amino substituents were electrochemically studied in CH2Cl2. Results were mutually
consistent with computational data showing that the carbene double bond of all complexes is
reduced pseudo reversibly to an anion radical, -Cr-C•. The Cr centers are oxidized in two
successive one electron transfer steps to Cr(II) via the Cr(I) intermediate. For all ferrocenyl
carbene complexes the Fe(II) is oxidized after the first oxidation of Cr. It was found that with
respect to the aryl substituents the donating effect decreases from Fc>Fu>Th. Stabilization
from the XR substituent, where XR = NHR, also resulted in lower redox potentials compared
to their OEt analogues.
The inclusion of ferrocene in the carbene substituent was done, as its redox activity and
increased donating effect are well known. Mono- and biscarbene complexes with ethoxy and
amino substituents of both chromium and tungsten were electrochemically studied. Again
experimental data were supported by computational studies. Similar to the ethoxy chromium
complexes, reduction of the W=C fragment to -W-C• was observed. However oxidation of the
Fc group occurred first before the electrochemically irreversible oxidation process for W(0) involving a three electron-mediated process as seen in chronocoulometric analyses. The
tungsten oxidation was restricted to a W0/II, consistent with computational studies, by the use
of the electrolyte [NnBu4][B(C6F5)4]. The short-lived W(II) species were calculated to be
stabilized by agostic CH···W interactions, similar to the chromium analogues. To extend
linkers between the metal-carbene termini and investigate metal-metal interaction,
biferrocenyl and 2,5-thienylbiferrocenyl tungsten(0) mono-and biscarbene complexes were
synthesized and studied by spectroelectrochemistry. A metal-metal charge transfer transition between the tungsten carbonyl increment and the biferrocenyl / 2,5-thienylbiferrocenyl unit
was confirmed by infrared spectroelectrochemical studies. The electronic interaction in the
corresponding cationic species can be described as weakly coupled class II systems according
to Robin and Day.
The cymantrenyl moiety, Mn(η5-C5H4)(CO)3, provides an interesting alternative to ferrocene
as an organometallic molecular tag, however the instability of the radical cation impairs its
use. Improved stability of the cation, monitored by electrochemical measurements, was
accomplished by substituting a carbonyl with a ferrocenyl Fischer carbene ligand resulting in
Mn(I) oxidation occuring at lower potentials than ferrocenyl oxidation. These uncommon
Fischer carbene complexes is the first organometallic multi-tags reported. The mono cationic
species, [CpMn(CO)2{=C(OEt)Fc}][PF6], could be isolated and characterized with ESR
analysis. Finally, transmetallation from the tungsten(0) Fischer carbene complexes yielded examples of
rare acyclic alkoxy- and aminocarbene complexes of gold(I). Single x-ray structures for all
complexes could be obtained including the novel ferrocenophane dinuclear biscarbene Au(I)
complex. All structures display unsupported aurophilic interactions, while the bridging
biscarbene shows a semi-supported Au-Au interaction. In the case of the furanyl/thienyl
methoxy monocarbene complexes, extended Au-Au interactions result in oligomeric
structures. Although this study is of a fundamental nature, it is imperative for the
understanding and design of gold compounds with specific applications.Thesis (PhD)--University of Pretoria, 2013.gm2014Chemistryunrestricte
Synthetic investigation of Mn(I) and Re(I) N-heterocyclic carbene complexes
The study involves synthetic approaches towards the preparation of novel NHC complexes of low valent rhenium and manganese transition metals. Diverse methods of synthesis were studied. The direct approach, in which the ylidene obtained from deprotonation of 1,3-bis(2,4,6- trimethylphenyl)imidazolium chloride was added to the metal substrate, proved to be unsuccessful as isolation of the free carbene should rather be performed in an argon filled glove box under extreme inert conditions. By way of further investigation the ylidene was prepared by in situ methods and then quenched with the metal substrate. Different bases for deprotonation purposes and reaction conditions were explored. All routes employed were investigated and compared using group VII transition metal substrates Re(CO)5Br, Mn(CO)5Br, Re2(CO)10 and Mn2(CO)10. Isolation and purification of these products proved to be very challenging due to the insolubility in some organic solvents with consequent problematic spectroscopic analyses of the complexes. The tendency of the products to undergo various side reactions is observed in all reactions. Specifically, hydrolysis of the imidazolium ligand, followed by vinyl formation, yielded the mesitylformamide compound (3). The results obtained for some of the monometal substrates indicated that the target complexes were formed but could not be isolated. However, the synthesis route employing deprotonation by nBuLi as base and [Mn2(CO)10] as dimetal substrate lead to the isolation of the target dinuclear complex [Mn2(CO)9IMes] (9). Other novel complexes obtained during the course of this study include the biscarbene tetrarhenium complex [Re2(CO)9.C(OEt)C4H2OC(OEt)Re2(CO)9] (12) and various side reaction products. In many cases, metal-metal bond cleavage and carbonyl insertion was observed, as is evident in the complex IMesH[ReO4] (6) and ketene product (13). Structural and theoretical studies were performed to investigate the bond character between the carbene ligand and the metal.Dissertation (MSc)--University of Pretoria, 2010.Chemistryunrestricte
Recent advances in the field of multicarbene and multimetal carbene complexes of the Fischer-type
This review article covers the development of Fischer carbene complexes since the year 2000, with specific
focus on carbene complexes bearing metal-containing fragments as substituents, as well as multicarbene
systems. The role of the metal-containing substituents on the character and reactivity of such complexes
are discussed. In addition, larger systems containing more than one carbene ligand are also covered (rodlike
biscarbenes, chelates, macrosystems, etc.) in terms of the synthesis, reactivity and structural aspects.http://www.elsevier.com/locate/ccrhb201
1,3-Bis(2,4,6-trimethylphenyl)-3H imidazol-1-ium tetraoxidorhenate(VII)
The title compound, (C21H25N2)[ReO4], was formed as the
unexpected product in an attempted synthesis of a
rhenium(I)–N-heterocyclic carbene (NHC) complex. The
compound has crystallographic mirror symmetry with both
the cation and the tetrahedral anion located across a mirror
plane. The cation and anion are linked by a C—H O
hydrogen bond.The University of Pretoria and the National Research Foundationhttp://journals.iucr.org/e/journalhomepage.htmlnf201
N-(2,4,6-Trimethylphenyl)formamide
The title compound, C10H13NO, was obtained as the unexpected, almost exclusive, product in the attempted synthesis of a manganese(I)–N-heterocyclic carbene (NHC) complex. The dihedral angle between the planes of the formamide moiety and the aryl ring is 68.06 (10)°. In the crystal, molecules are linked by N—H⋯O hydrogen bonds, forming infinite chains along the c axis
Monitoring Patient Response to Pembrolizumab With Peripheral Blood Exhaustion Marker Profiles
Exhausted T cells are effector T cells that are silenced due to continuous T cell receptor (TCR) stimulation from persistent antigens. Characteristics of exhaustion include the increased expression of multiple inhibitory receptors such as programme death-1[PD-1], lymphocyte activation gene 3 [LAG-3], T cell Ig and mucin domain [TIM-3], the loss of effector cytokine secretion and altered transcriptional profile. The PD-1/PD-L1 interaction induces functional exhaustion of tumor-reactive cytotoxic T cells and interferes with anti-tumor T cell immunity. T cell exhaustion has been observed in metastatic melanoma patients where the exhaustion of tumor specific T cells suggests that tumor clearance has been impeded and contributed to tumor immune escape. Checkpoint immunotherapies are antibodies designed to block the interaction between the inhibitory receptors expressed on T cells and their respective ligands. Therapies such as anti-PD-1 (Pembrolizumab and Nivolumab) block these inhibitory receptors and are associated with a significant improvement in overall survival and progression free survival. However, only 20–40% of metastatic melanoma patients experience long-term benefit. In a cohort of 16 metastatic melanoma patients receiving pembrolizumab, blood was serially collected before each infusion (mean 8.3; range 1–12 cycles). The presence of inhibitory markers LAG-3, TIM-3, and PD-1 on the surface of T cells was examined and assessed in relation to patient response to identify if inhibitory markers can be used to differentiate responders from non-responders for Pembrolizumab. We confirmed that across a range of cycles (range 1–26) of pembrolizumab, PD-1 expression was significantly higher on CD4+ T cells from non-responders compared to responders and TIM-3 expressed on the surface of CD8+ T cells was significantly higher in non-responders compared to responders. This longitudinal data confirms previous studies that assessed single timepoints. This study provides preliminary evidence that PD-1 and TIM-3 may be predictive of non-responders when assessed over multiple treatment cycles
(Spectro)electrochemical investigations on (ferrocenyl)thiophenes modified by tungsten Fischer carbenes
Please abstract in the article.National Research Foundation,
South Africa and Fonds der Chemischen Industrie and Chemifonds Fellowships.http://www.elsevier.com/locate/jorganchem2015-12-31hb201
Electrochemical and computational study of tungsten(0) ferrocene complexes: observation of the mono-oxidized tungsten(0) ferrocenium species and intramolecular electronic interactions
The series [(CO)5W=C(XR)Fc], 1 (XR = OEt) and 3 (XR = NHBu) as well as
[(CO)5W=C(XR)-Fc'-(XR)C=W(CO)5], 2 (XR = OEt) and 4 (XR = NHBu) of mono- and
biscarbene tungsten(0) complexes with Fc = FeII(C5H5)(C5H4) for monosubstituted derivatives
and Fc¢ = FeII(C5H4)2 for disubstituted derivatives were synthesized and characterized
spectroscopically. The oxidized ferrocenium complex [1+]•PF6 was also synthesized and
characterized. Electrochemical and computational studies were mutually consistent in confirming
the sequence of redox events for the carbene derivatives 1 - 4 as first a carbene double bond reduction to a radical anion, -W-C•, at peak cathodic potentials smaller than -2 V, then a
ferrocenyl group oxidation in the range 0.206 < Eo' < 0.540 V and finally an electrochemically
irreversible three-electron W(0) oxidation at Epa > 0.540 V vs. FcH/FcH+ in CH2Cl2 /
[(nBu4)N][PF6]. This contrasts the sequence of oxidation events in ferrocenylcarbene complexes
of chromium where Cr(0) is first oxidised in a one electron transfer process, then the ferrocenyl
group, and finally formation of a Cr(II) species. The unpaired electron of the reductively formed
radical anion is mainly located on the carbene carbon atom. Electronic interactions between two
carbene double bonds (for biscarbenes 2 and 4) as well as between two W centers (for 4) were
evident. Differences in redox potentials between the “a” and “b” components of the threeelectron
W oxidation of 4 in CH2Cl2 or CH3CN / [(nBu4)N][PF6] are DEo' = Epa W(0) oxd 1b – Epa W(0)
oxd 1a = ca. 51 and 337 mV respectively. Tungsten oxidation was restricted to a W0/II couple in
CH2Cl2 / [(nBu4)N][B(C6F5)4]. From the computational results, the short-lived W(II) species
were observed to be stabilized by agostic CH···W interactions.National Research Foundation, South Africa, (DIB, Grant number 76226;
JCS, Grant number 81829), and by the Spanish MICINN and CAM (IF, Grants CTQ2010-20714-CO2-01/BQU, Consolider-Ingenio 2010, CSD2007-00006, S2009/PPQ-1634).http://pubs.acs.org/journal/orgnd7hb201
Metal–metal interaction in Fischer carbene complexes : a study of ferrocenyl and biferrocenyl tungsten alkylidene complexes
A series of ferrocenyl (Fc = ferrocenyl; fc = ferrocen-1,1'-diyl) and biferrocenyl (Bfc = 1',1''-biferrocenyl; bfc
= 1',1''-biferrocen-1,1'''-diyl) mono- and biscarbene tungsten(0) complexes of the type [(CO)5W=C(OMe)R] (1, R = Fc; 3, R
= Bfc) and [(CO)5W=C(OMe)-R'-(OMe)C=W(CO)5] (2, R' = fc; 4, R' = bfc) were synthesized according to the classical
synthetic methodology by reacting W(CO)6 with LiR (R = Fc, fc, bfc), followed by a subsequent alkylation using methyl
trifluoromethanesulfonate. Electrochemical investigations were carried out on these complexes to get a closer insight into the
electronic properties of 1 - 4. The ferrocenyl and biferrocenyl moieties in 1 – 4 show reversible one electron redox events. It
was further found that the Fischer carbene unit is reducible in an electrochemical one electron transfer process. For the
tungsten carbonyl moieties, irreversible oxidation processes were found. In addition, charge transfer studies were performed on 1
- 4 by the use of in situ UV-Vis-NIR and infrared spectroelectrochemical techniques. During the UV-Vis-NIR investigations
typical low energy transitions for the mixed-valent biferrocenyl unit were found. A further observed high energy NIR
absorption is attributed to a metal-metal charge transfer transition between the tungsten carbonyl fragment and the
ferrocenyl/biferrocenyl group in the corresponding oxidized states, which can be described as class II systems according to
Robin and Day. This assignment was verified by infrared spectroelectrochemical studies. The electrochemical investigations
are supported by DFT calculations. The structural properties of 1 - 4 in the solid state were investigated by single-crystal Xray
diffraction studies showing no substituent effects on bond lengths and angles. The biferrocenyl derivatives exhibit synconformation
of the ferrocenyl and carbene building blocks.D.I.B. and B.v.d.W. acknowledge the National Research Foundation, South Africa for financial support (Grant number 76226). We are grateful to the Fonds der Chemischen Industrie for financial support. J.M.S. and M.K. thank the FCI for Chemiefonds Fellowships.http://pubs.acs.org/journal/inocajhb201
Fischer-type gold(I) carbene complexes stabilized by aurophilic interactions
The synthesis and structure of rare acyclic alkoxy- and aminocarbene complexes of gold(I) are reported, including a novel ferrocenophane dinuclear biscarbene complex. X-Ray
diffraction analyses and DFT calculations reveal that these complexes are stabilized by genuine aurophilic interactions.National Research Foundation,South Africa (D.I.B., Grant number 76226), and the Spanish MICINN and CAM (I.F., Grants CTQ2010-20714-CO2-01/BQU, Consolider-Ingenio 2010, CSD2007-00006,S2009/PPQ-1634).http://www.rsc.org/dalton2015-02-28hb201