Synergy between Experimental and Computational Chemistry Reveals the Mechanism of Decomposition of Nickel–Ketene Complexes

A series of (dppf)­Ni­(ketene) complexes were synthesized and fully characterized. In the solid state, the complexes possess η²-(C,O) coordination of the ketene in an overall planar configuration. They display similar structure in solution, except in some cases, the η²-(C,C) coordination mode is also detected. A combination of kinetic analysis and DFT calculations reveals the complexes undergo thermal decomposition by isomerization from η²-(C,O) to η²-(C,C) followed by scission of the CC bond, which is usually rate limiting and results in an intermediate carbonyl carbene complex. Subsequent rearrangement of the carbene ligand is rate limiting for electron poor and sterically large ketenes, and results in a carbonyl alkene complex. The alkene readily dissociates, affording alkenes and (dppf)­Ni­(CO)₂. Computational modeling of the decarbonylation pathway with partial phosphine dissociation reveals the barrier is reduced significantly, explaining the instability of ketene complexes with monodentate phosphines

Candidoses invasives en réanimation : données épidémiologiques, élaboration d’un score prédictif et mise au point de PCR pour le diagnostic

Patients in intensive care units (ICU) are at very high risk of invasive candidiasis associated with high mortality rate. Candida species are the third cause of septicemia. Clinical signs lack of specificity and blood cultures lack of sensitivity, and therefore the diagnosis remains a challenge. In order to improve the identification of patients with invasive candidiasis, predictive rules, biomarkers and PCR have been developed. The first part of this work describes the evolution over a ten years period in one ICU in Candida species distribution, susceptibility to antifungal drugs and consumption of antifungal agents. Changes in antifungal drug consumption were observed but they were not associated with significant changes in fungal ecology or with the emergence of resistant species. In a second part, we present a prospective, observational and bicentric study performed in 435 non-neutropenic patients in ICU. Several variables (risk factors of invasive candidiasis, Candida colonization, mannan antigen and anti-mannan antibodies) were analyzed and a predictive score of invasive candidiasis has been developed. Finally, the last part presents the development of Candida real-time PCR in blood, as well as the evaluation of a digital PCR.Les patients de réanimation sont des patients à très haut risque de survenue de candidoses invasives associées à une importante mortalité. Les espèces du genre Candida sont retrouvées en troisième position des agents infectieux les plus fréquemment isolés au cours des septicémies. Le diagnostic reste difficile en raison d’une clinique aspécifique et d’une sensibilité médiocre des hémocultures. Des scores prédictifs, des biomarqueurs ou encore des PCR ont été développés de manière à améliorer le diagnostic et l’identification des patients à risque. Dans ce travail, la première partie présente les données de l’évolution de l’écologie fongique, des candidoses invasives, des prescriptions d’antifongiques et des sensibilités aux antifongiques sur une période de dix ans dans un service de réanimation. Au cours de cette période, les changements observés dans la prescription d’antifongiques n’ont pas entrainé de modifications significatives de l’écologie fongique ni d’apparition de résistances. Dans une deuxième partie, nous présentons les résultats d’une étude prospective observationnelle bicentrique réalisée chez 435 patients non neutropéniques de réanimation. L’analyse de plusieurs variables (facteurs de risque de candidose invasive, colonisation à Candida sp., dosages d’antigène mannane et d’anticorps anti-mannane) a permis l’élaboration d’un score prédictif de survenue de candidose invasive. Finalement, la dernière partie du travail présente la mise au point de PCR Candida en temps réel dans le sang ainsi qu’une évaluation de la technologie de digital PCR

Regioselective Aliphatic Carbon–Carbon Bond Cleavage by a Model System of Relevance to Iron-Containing Acireductone Dioxygenase

Mononuclear Fe­(II) complexes ([(6-Ph₂TPA)­Fe­(PhC­(O)­C­(R)­C­(O)­Ph)]­X (<b>3-X</b>: R = OH, X = ClO₄ or OTf; <b>4</b>: R = H, X = ClO₄)) supported by the 6-Ph₂TPA chelate ligand (6-Ph₂TPA = <i>N</i>,<i>N</i>-bis­((6-phenyl-2-pyridyl)­methyl)-<i>N</i>-(2-pyridylmethyl)­amine) and containing a β-diketonate ligand bound via a six-membered chelate ring have been synthesized. The complexes have all been characterized by ¹H NMR, UV–vis, and infrared spectroscopy and variably by elemental analysis, mass spectrometry, and X-ray crystallography. Treatment of dry CH₃CN solutions of <b>3-OTf</b> with O₂ leads to oxidative cleavage of the C(1)–C(2) and C(2)–C(3) bonds of the acireductone via a dioxygenase reaction, leading to formation of carbon monoxide and 2 equiv of benzoic acid as well as two other products not derived from dioxygenase reactivity: 2-oxo-2-phenylethylbenzoate and benzil. Treatment of CH₃CN/H₂O solutions of <b>3-X</b> with O₂ leads to the formation of an additional product, benzoylformic acid, indicative of the operation of a new reaction pathway in which only the C(1)–C(2) bond is cleaved. Mechanistic studies show that the change in regioselectivity is due to the hydration of a vicinal triketone intermediate in the presence of both an iron center and water. This is the first structural and functional model of relevance to iron-containing acireductone dioxygenase (Fe-ARD′), an enzyme in the methionine salvage pathway that catalyzes the regiospecific oxidation of 1,2-dihydroxy-3-oxo-(<i>S</i>)-methylthiopentene to form 2-oxo-4-methylthiobutyrate. Importantly, this model system is found to control the regioselectivity of aliphatic carbon–carbon bond cleavage by changes involving an intermediate in the reaction pathway, rather than by the binding mode of the substrate, as had been proposed in studies of acireductone enzymes

Influence of supporting ligand microenvironment on the aqueous stability and visible light-induced CO-release reactivity of zinc flavonolato species

<div><p>The visible light-induced CO-release reactivity of the zinc flavonolato complex [(6-Ph₂TPA)Zn(3-Hfl)]ClO₄ (<b>1</b>) has been investigated in 1 : 1 H₂O : DMSO. Additionally, the effect of ligand secondary microenvironment on the aqueous stability and visible light-induced CO-release reactivity of zinc flavonolato species has been evaluated through the preparation, characterization, and examination of the photochemistry of compounds supported by chelate ligands with differing secondary appendages, [(TPA)Zn(3-Hfl)]ClO₄ (<b>3</b>; TPA = tris-2-(pyridylmethyl)amine) and [(bnpapa)Zn(3-Hfl)]ClO₄ (<b>4</b>; bnpapa = <i>N</i>,<i>N</i>-bis((6-neopentylamino-2-pyridyl)methyl)-<i>N</i>-((2-pyridyl)methyl)amine)). Compound <b>3</b> undergoes reaction in 1 : 1 H₂O : DMSO resulting in the release of the free neutral flavonol. Irradiation of acetonitrile solutions of <b>3</b> and <b>4</b> at 419 nm under aerobic conditions results in quantitative, photoinduced CO-release. However, the reaction quantum yields under these conditions are lower than that exhibited by <b>1</b>, with <b>4</b> exhibiting an especially low quantum yield. Overall, the results of this study indicate that positioning a zinc flavonolato moiety within a hydrophobic microenvironment is an important design strategy toward further developing such compounds as CO-release agents for use in biological systems.</p></div

Halide-Promoted Dioxygenolysis of a Carbon–Carbon Bond by a Copper(II) Diketonate Complex

A mononuclear Cu­(II) chlorodiketonate complex was prepared, characterized, and found to undergo oxidative aliphatic carbon–carbon bond cleavage within the diketonate unit upon exposure to O₂ at ambient temperature. Mechanistic studies provide evidence for a dioxygenase-type C–C bond cleavage reaction pathway involving trione and hypochlorite intermediates. Significantly, the presence of a catalytic amount of chloride ion accelerates the oxygen activation step via the formation of a Cu–Cl species, which facilitates monodentate diketonate formation and lowers the barrier for O₂ activation. The observed reactivity and chloride catalysis is relevant to Cu­(II) halide-catalyzed reactions in which diketonates are oxidatively cleaved using O₂ as the terminal oxidant. The results of this study suggest that anion coordination can play a significant role in influencing copper-mediated oxygen activation in such systems

First Row Transition Metal(II) Thiocyanate Complexes, and Formation of 1‑, 2‑, and 3‑Dimensional Extended Network Structures of M(NCS)₂(Solvent)₂ (M = Cr, Mn, Co) Composition

The reaction of first row transition M^II ions with KSCN in various solvents form tetrahedral (NMe₄)₂[M^II(NCS)₄] (M = Fe, Co), octahedral <i>trans</i>-M^II(NCS)₂(Sol)₄ (M = Fe, V, Ni; Sol = MeCN, THF), and K₄[M^II(NCS)₆] (M = V, Ni). The reaction of M­(NCS)₂(OCMe₂)₂ (M = Cr, Mn) in MeCN and [Co­(NCMe)₆]­(BF₄)₂ and KSCN in acetone and after diffusion of diethyl ether form M­(NCS)₂(Sol)₂ that structurally differ as they form one-dimensional (1-D) (M = Co; Sol = THF), two-dimensional (2-D) (M = Mn; Sol = MeCN), and three-dimensional (3-D) (M = Cr; Sol = MeCN) extended structures. 1-D Co­(NCS)₂(THF)₂ has <i>trans</i>-THFs, while the acetonitriles have a <i>cis</i> geometry for 2- and 3-D M­(NCS)₂(NCMe)₂ (M = Cr, Mn). 2-D Mn­(NCS)₂(NCMe)₂ is best described as Mn^II(μ_N,N-NCS)­(μ_N,S-NCS)­(NCMe)₂ [= Mn₂(μ_N,N-NCS)₂(μ_N,S-NCS)₂(NCMe)₄] with the latter μ_N,S-NCS providing the 2-D connectivity. In addition, the reaction of Fe­(NCS)₂(OCMe₂)₂ and 7,7,8,8-tetracyanoquino-<i>p</i>-dimethane (TCNQ) forms 2-D structured Fe^II(NCS)₂TCNQ. The magnetic behavior of 1-D Co­(NCS)₂(THF)₂ can be modeled by a 1-D Fisher expression (<i>H</i> = −2<i>J</i>S_<i>i</i>·S_<i>j</i>) with <i>g</i> = 2.4 and <i>J</i>/<i>k</i>_B = 0.68 K (0.47 cm^–1) and exhibit weak ferromagnetic coupling. Cr­(NCS)₂(NCMe)₂ and Fe^II(NCS)₂TCNQ magnetically order as antiferromagnets with <i>T</i>_c’s of 37 and 29 K, respectively, while Mn­(NCS)₂(NCMe)₂ exhibits strong antiferromagnetic coupling. M­(NCS)₂(THF)₄ and K₄[M­(NCS)₆] (M = V, Ni) are paramagnets with weak coupling between the octahedral metal centers

Anion Effects in Oxidative Aliphatic Carbon–Carbon Bond Cleavage Reactions of Cu(II) Chlorodiketonate Complexes

Aliphatic oxidative carbon–carbon bond cleavage reactions involving Cu­(II) catalysts and O₂ as the terminal oxidant are of significant current interest. However, little is currently known regarding how the nature of the Cu­(II) catalyst, including the anions present, influence the reaction with O₂. In previous work, we found that exposure of the Cu­(II) chlorodiketonate complex [(6-Ph₂TPA)­Cu­(PhC­(O)­CClC­(O)­Ph)]­ClO₄ (<b>1</b>) to O₂ results in oxidative aliphatic carbon–carbon bond cleavage within the diketonate unit, leading to the formation of benzoic acid, benzoic anhydride, benzil, and 1,3-diphenylpropanedione as organic products. Kinetic studies of this reaction revealed a slow induction phase followed by a rapid decay of the absorption features of <b>1</b>. Notably, the induction phase is not present when the reaction is performed in the presence of a catalytic amount of chloride anion. In the studies presented herein, a combination of spectroscopic (UV–vis, EPR) and density functional theory (DFT) methods have been used to examine the chloride and benzoate ion binding properties of <b>1</b> under anaerobic conditions. These studies provide evidence that each anion coordinates in an axial position of the Cu­(II) center. DFT studies reveal that the presence of the anion in the Cu­(II) coordination sphere decreases the barrier for O₂ activation and the formation of a Cu­(II)–peroxo species. Notably, the chloride anion more effectively lowers the barrier associated with O–O bond cleavage. Thus, the nature of the anion plays an important role in determining the rate of reaction of the diketonate complex with O₂. The same type of anion effects were observed in the O₂ reactivity of the simple Cu­(II)–bipyridine complex [(bpy)­Cu­(PhC­(O)­C­(Cl)­C­(O)­Ph)­ClO₄] (<b>3</b>)

First Row Transition Metal(II) Thiocyanate Complexes, and Formation of 1‑, 2‑, and 3‑Dimensional Extended Network Structures of M(NCS)₂(Solvent)₂ (M = Cr, Mn, Co) Composition

The reaction of first row transition M^II ions with KSCN in various solvents form tetrahedral (NMe₄)₂[M^II(NCS)₄] (M = Fe, Co), octahedral <i>trans</i>-M^II(NCS)₂(Sol)₄ (M = Fe, V, Ni; Sol = MeCN, THF), and K₄[M^II(NCS)₆] (M = V, Ni). The reaction of M­(NCS)₂(OCMe₂)₂ (M = Cr, Mn) in MeCN and [Co­(NCMe)₆]­(BF₄)₂ and KSCN in acetone and after diffusion of diethyl ether form M­(NCS)₂(Sol)₂ that structurally differ as they form one-dimensional (1-D) (M = Co; Sol = THF), two-dimensional (2-D) (M = Mn; Sol = MeCN), and three-dimensional (3-D) (M = Cr; Sol = MeCN) extended structures. 1-D Co­(NCS)₂(THF)₂ has <i>trans</i>-THFs, while the acetonitriles have a <i>cis</i> geometry for 2- and 3-D M­(NCS)₂(NCMe)₂ (M = Cr, Mn). 2-D Mn­(NCS)₂(NCMe)₂ is best described as Mn^II(μ_N,N-NCS)­(μ_N,S-NCS)­(NCMe)₂ [= Mn₂(μ_N,N-NCS)₂(μ_N,S-NCS)₂(NCMe)₄] with the latter μ_N,S-NCS providing the 2-D connectivity. In addition, the reaction of Fe­(NCS)₂(OCMe₂)₂ and 7,7,8,8-tetracyanoquino-<i>p</i>-dimethane (TCNQ) forms 2-D structured Fe^II(NCS)₂TCNQ. The magnetic behavior of 1-D Co­(NCS)₂(THF)₂ can be modeled by a 1-D Fisher expression (<i>H</i> = −2<i>J</i>S_<i>i</i>·S_<i>j</i>) with <i>g</i> = 2.4 and <i>J</i>/<i>k</i>_B = 0.68 K (0.47 cm^–1) and exhibit weak ferromagnetic coupling. Cr­(NCS)₂(NCMe)₂ and Fe^II(NCS)₂TCNQ magnetically order as antiferromagnets with <i>T</i>_c’s of 37 and 29 K, respectively, while Mn­(NCS)₂(NCMe)₂ exhibits strong antiferromagnetic coupling. M­(NCS)₂(THF)₄ and K₄[M­(NCS)₆] (M = V, Ni) are paramagnets with weak coupling between the octahedral metal centers

Anion Effects in Oxidative Aliphatic Carbon–Carbon Bond Cleavage Reactions of Cu(II) Chlorodiketonate Complexes

Aliphatic oxidative carbon–carbon bond cleavage reactions involving Cu­(II) catalysts and O₂ as the terminal oxidant are of significant current interest. However, little is currently known regarding how the nature of the Cu­(II) catalyst, including the anions present, influence the reaction with O₂. In previous work, we found that exposure of the Cu­(II) chlorodiketonate complex [(6-Ph₂TPA)­Cu­(PhC­(O)­CClC­(O)­Ph)]­ClO₄ (<b>1</b>) to O₂ results in oxidative aliphatic carbon–carbon bond cleavage within the diketonate unit, leading to the formation of benzoic acid, benzoic anhydride, benzil, and 1,3-diphenylpropanedione as organic products. Kinetic studies of this reaction revealed a slow induction phase followed by a rapid decay of the absorption features of <b>1</b>. Notably, the induction phase is not present when the reaction is performed in the presence of a catalytic amount of chloride anion. In the studies presented herein, a combination of spectroscopic (UV–vis, EPR) and density functional theory (DFT) methods have been used to examine the chloride and benzoate ion binding properties of <b>1</b> under anaerobic conditions. These studies provide evidence that each anion coordinates in an axial position of the Cu­(II) center. DFT studies reveal that the presence of the anion in the Cu­(II) coordination sphere decreases the barrier for O₂ activation and the formation of a Cu­(II)–peroxo species. Notably, the chloride anion more effectively lowers the barrier associated with O–O bond cleavage. Thus, the nature of the anion plays an important role in determining the rate of reaction of the diketonate complex with O₂. The same type of anion effects were observed in the O₂ reactivity of the simple Cu­(II)–bipyridine complex [(bpy)­Cu­(PhC­(O)­C­(Cl)­C­(O)­Ph)­ClO₄] (<b>3</b>)

Half-Sandwich Ruthenium-Phosphine Complexes with Pentadienyl and Oxo- and Azapentadienyl Ligands

Treatment of RuCl₂(PPh₃)₃ and RuHCl­(PPh₃)₃ with the tin compound CH₂C­(Me)­CHC­(Me)­CH₂SnMe₃ gives the corresponding acyclic pentadienyl half-sandwich (η⁵-CH₂C­(Me)­CHC­(Me)­CH₂)­RuX­(PPh₃)₂ [X = Cl, (<b>2</b>); H, (<b>3</b>)]. The steric congestion in <b>2</b> is most effectively relieved by formation of the cyclometalated complex (η⁵-CH₂C­(Me)­CHC­(Me)­CH₂)­Ru(C₆H₄PPh₂)­(PPh₃) (<b>4</b>). Addition of 1 equiv of PHPh₂ to (η⁵-CH₂CHCHCHCH₂)­RuCl­(PPh₃)₂ (<b>1</b>) affords the chiral complex (η⁵-CH₂CHCHCHCH₂)­RuCl­(PPh₃)­(PHPh₂) (<b>5</b>), while compound (η⁵-CH₂C­(Me)­CHC­(Me)­CH₂)­RuCl­(PPh₃)­(PHPh₂)] (<b>6</b>) is directly obtained from the reaction of RuCl₂(PPh₃)₃ with CH₂C­(Me)­CHC­(Me)­CH₂Sn­(Me)₃ and PHPh₂. Treatment of RuCl₂(PPh₃)₃ with the corresponding Me₃SnCH₂CHCHCHNR (R = Cy, <i>t-</i>Bu) affords (1-3,5-η-CH₂CHCHCHNCy)­RuCl­(PPh₃)₂ (<b>7</b>) and [1-3,5-η-CH₂CHCHCHN­(<i>t</i>-Bu)]RuCl­(PPh₃)₂ (<b>8</b>). The hydrolysis of <b>7</b>, on a silica gel chromatography column, allows the isolation of RuCl­(η⁵-CH₂CHCHCHO)­(PPh₃)₂ (<b>9</b>). The azapentadienyl complex <b>7</b> reacts with 1 equiv of PHPh₂ to afford [1-3,5-η-CH₂CHCHCHN­(Cy)]­RuCl­(PPh₃)­(PHPh₂) (<b>10</b>), while the corresponding product [1-3,5-η-CH₂CHCHCHN­(<i>t</i>-Bu)]­RuCl­(PPh₃)­(PHPh₂) (<b>11</b>) from <b>8</b> is only observed through ¹H and ³¹P NMR spectroscopy as a mixture of isomers. Two equivalents of PHPh₂ gives spectroscopic evidence of [η³-CH₂CHCHCHN­(<i>t</i>-Bu)]­RuCl­(PHPh₂)₃. A mixture of products [η⁵-CH₂C­(Me)­CHC­(Me)­O]­RuCl­(PPh₃)₂ (<b>12</b>) and [η⁵-CH₂C­(Me)­CHC­(Me)­O]­RuH­(PPh₃)₂ (<b>13</b>) is obtained from reaction of RuCl₂(PPh₃)₃ with Li­[CH₂C­(Me)­CHC­(Me)­O]. In contrast, the oxopentadienyl compound <b>13</b> is cleanly formed from RuHCl­(PPh₃)₃ and Li­[CH₂C­(Me)­CHC­(Me)­O]. An attempt to separate compounds <b>12</b> and <b>13</b> by crystallization gives an orthometalated product [η⁵-CH₂C­(Me)­CHC­(Me)­O]­Ru­(C₆H₄PPh₂)­(PPh₃) (<b>14</b>), which is the oxopentadienyl analogue to <b>4</b>. The bulky [1-3,5-η-CH₂C­(<i>t</i>-Bu)­CHC­(<i>t</i>-Bu)­O]­RuH­(PPh₃)₂ (<b>15</b>) analogue to <b>13</b> has also been prepared from RuHCl­(PPh₃)₃ and Li­[CH₂C­(<i>t</i>-Bu)­CHC­(<i>t</i>-Bu)­O]. Compounds <b>3</b>, <b>5</b>, <b>6</b>, <b>7</b>, and <b>12</b>–<b>15</b> have been structurally characterized. The preferred heteropentadienyl orientations and the relative positions of the H, Cl, PPh₃, and PHPh₂ ligands have been established in the piano-stool structures for all compounds, and it can be definitively surmised that the chemistry involved in the heteropentadienyl half-sandwich compounds studied is dominated by steric effects