References of "De Tullio, Pascal"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailInhibition of PDH Kinase as a new therapeutic target for Age-related Macular Degeneration (AMD)
Arslan, Deniz ULg; Pirotte, Bernard ULg; De Tullio, Pascal ULg et al

Poster (2014, June)

Metabolomics is one of the most recent technologies in the world of Omics sciences. It aims at studying metabolome, which is composed of small molecular weight organic molecules (called metabolites) of a ... [more ▼]

Metabolomics is one of the most recent technologies in the world of Omics sciences. It aims at studying metabolome, which is composed of small molecular weight organic molecules (called metabolites) of a cell, an organism or a biological system. This approach gives rise to a growing number of applications in many areas, such as biomarkers discovery, clinical studies, drug efficacy and toxicity evaluation, diagnostic tools, quality control. One of the most interesting features of metabolomics is its capability to extract biochemical information reflecting biological events and then to be a powerful tool in the knowledge of the aetiology of some pathologies. Indeed, it is clear that every disease could alter more or less drastically the metabolic profile of the patients. Then a metabolomics approach could highlight the biochemical pathways affected and could allow the identification of new putative therapeutic strategies or targets that could be useful in a new drug discovery strategy. As proteomics, metabolomics approach represents a new and powerful tool for Medicinal Chemistry. Age-related Macular Degeneration (AMD) is a leading cause of vision loss in the western world among people aged 50 or older. 90% of all vision loss due to AMD results from the exudative form, which is characterized by choroidal neovascularization (CNV). Age-related changes that induce pathologic CNV are incompletely understood. A successful application of anti-VEGF approaches in the clinic is obviously a turning point in AMD treatment. Nevertheless, despite such important advances, critical issues remain to be addressed. To better understand the aetiology of this pathology, we used and improved a murine model of laser-induced choroidal neovascularization and applied a 1H NMR metabolomics study. This approach leads to the emergence of different putative biomarkers and to the validation of the CNV model for an experimental study of AMD. Among these “biomarkers”, lactate appears to be clearly involved in the development of AMD. The modulation of their plasma concentration by treatment of the animals with synthetic compounds and more specifically Pyruvate DesHydrogenase Kinase inhibitors (PDHK) significantly decrease the impact of laser induced CNV. Starting from these results, the development of new PDHK inhibitors could open the way to innovative treatment opportunities in AMD disease. [less ▲]

Detailed reference viewed: 54 (17 ULg)
See detailGlucose-dependent metabolic reprogramming in HDAC5-depleted cancer cells
Hendrick, Elodie ULg; Peixoto, Paul ULg; Polese, Catherine ULg et al

Poster (2014, May 19)

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum ... [more ▼]

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1 The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of subunits of the complex I of the mitochondrial respiratory chain (NDUFB5-NDUFA3) as well as anti-oxydant proteins (Ferritin, Metalothionein,¿) through modulation of mRNA stability. Therefore, HDAC5 depletion causes a significant increase of ROS production inducing both apoptosis and mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). This HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glycolysis and glucose. Indeed, interference with glucose supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Our study demonstrated for the first time that specific HDAC5 inhibition induces metabolic reprogramming and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. Presenting author e-mail: elodie.hendrick@student.ulg.ac.be [less ▲]

Detailed reference viewed: 14 (0 ULg)
See detailGlucose-dependent metabolic reprogramming in HDAC5-depleted cancer cells
Hendrick, Elodie ULg; Peixoto, Paul ULg; Polese, Catherine ULg et al

Poster (2014, April 25)

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum ... [more ▼]

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival (PEIXOTO et al., 2012). The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of subunits of the complex I of the mitochondrial respiratory chain (NDUFB5-NDUFA3) as well as anti-oxydant proteins (Ferritin, Metalothionein,¿) through modulation of mRNA stability. Therefore, HDAC5 depletion causes a significant increase of ROS production inducing both apoptosis and mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). This HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glycolysis and glucose. Indeed, interference with glucose supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Our study demonstrated for the first time that specific HDAC5 inhibition induces metabolic reprogramming and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. Acknowledgements This work fiancially suppoted by a grant of F.R.S .-FNRS (contract n° 7.4515.12F). E Hendrick is recipient of a Televie fellowship. References PEIXOTO et al., (2012) Cell Death and Differentiation. 7:1239-52. [less ▲]

Detailed reference viewed: 8 (1 ULg)
See detailComplex I Mitochondrial Dysfunction in HDAC5-depleted Cancer Cells Induces Glucose-dependent Metabolic Reprogramming
Hendrick, Elodie ULg; Peixoto, Paul ULg; Polese, Catherine ULg et al

Poster (2014, February 01)

Introduction : Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure ... [more ▼]

Introduction : Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1. Aims : The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Methods and results : Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of NDUFB5, a subunit of the complex I of the mitochondrial respiratory chain through modulation of mRNA stability. HDAC5 depletion-induced NDUFB5 downregulation causes a significant increase of ROS production and induces uncoupled mitochondrial respiration. In addition, this HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glucose. Indeed, interference with glucose supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Conclusions : Our study demonstrated for the first time that specific HDAC5 inhibition induces alteration of NDUFB5 gene expression by altering mRNA stability and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. [less ▲]

Detailed reference viewed: 15 (0 ULg)
See detailComplex I Mitochondrial Dysfunction in HDAC5-depleted Cancer Cells Induces Glucose-dependent Metabolic Reprogramming
Hendrick, Elodie ULg; Peixoto, Paul ULg; Matheus, Nicolas ULg et al

Poster (2014, January 27)

Introduction : Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure ... [more ▼]

Introduction : Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1. Aims : The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Methods and results : Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of NDUFB5, a subunit of the complex I of the mitochondrial respiratory chain through modulation of mRNA stability. HDAC5 depletion-induced NDUFB5 downregulation causes a significant increase of ROS production and induces uncoupled mitochondrial respiration. In addition, this HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glucose. Indeed, interference with glucose supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Conclusions : Our study demonstrated for the first time that specific HDAC5 inhibition induces alteration of NDUFB5 gene expression by altering mRNA stability and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. [less ▲]

Detailed reference viewed: 8 (0 ULg)
Full Text
Peer Reviewed
See detailAn Easy, Convenient Cell and Tissue Extraction Protocol for Nuclear Magnetic Resonance Metabolomics.
Matheus, Nicolas ULg; Hansen, Sylvain ULg; Rozet, Eric ULg et al

in Phytochemical analysis : PCA (2014), 25

INTRODUCTION: As a complement to the classic metabolomics biofluid studies, the visualisation of the metabolites contained in cells or tissues could be a very powerful tool to understand how the local ... [more ▼]

INTRODUCTION: As a complement to the classic metabolomics biofluid studies, the visualisation of the metabolites contained in cells or tissues could be a very powerful tool to understand how the local metabolism and biochemical pathways could be affected by external or internal stimuli or pathologies. Therefore, extraction and/or lysis is necessary to obtain samples adapted for use with the current analytical tools (liquid NMR and MS). These extraction or lysis work-ups are often the most labour-intensive and rate-limiting steps in metabolomics, as they require accuracy and repeatability as well as robustness. Many of the procedures described in the literature appear to be very time-consuming and not easily amenable to automation. OBJECTIVE: To find a fast, simplified procedure that allows release of the metabolites from cells and tissues in a way that is compatible with NMR analysis. METHODS: We assessed the use of sonication to disrupt cell membranes or tissue structures. Both a vibrating probe and an automated bath sonicator were explored. RESULTS: The application of sonication as the disruption procedure led to reproducible NMR spectral data compatible with metabolomics studies. This method requires only a small biological tissue or cell sample, and a rapid, reduced work-up was applied before analysis. The spectral patterns obtained are comparable with previous, well-described extraction protocols. CONCLUSION: The rapidity and the simplicity of this approach could represent a suitable alternative to the other protocols. Additionally, this approach could be favourable for high- throughput applications in intracellular and intratissular metabolite measurements. Copyright (c) 2014 John Wiley & Sons, Ltd. [less ▲]

Detailed reference viewed: 75 (21 ULg)
Full Text
Peer Reviewed
See detailSperm Motility and Lactate production at different sperm concentrations
Ponthier, Jérôme ULg; De Tullio, Pascal ULg; Blommaert, Didier ULg et al

in Journal of Equine Veterinary Science (2014, January), 34(1), 75-76

Lactate production is associated with total spermatozoa concentration. It negatively affects preservation of total and progressive motility, showing an effect of by-products of anaerobic metabolism on ... [more ▼]

Lactate production is associated with total spermatozoa concentration. It negatively affects preservation of total and progressive motility, showing an effect of by-products of anaerobic metabolism on long-term storage. Moreover, our data show that non-progressive motile spermatozoa are highly associated to lactate concentration, and thus, anaerobic glycolysis. More studies are required to determine relative contributions of aerobiosis and anaerobiosis to spermatozoa motility under different storage conditions. [less ▲]

Detailed reference viewed: 70 (24 ULg)
Full Text
Peer Reviewed
See detailBlocking lipid synthesis overcomes tumor re-growth and metastasis after anti-angiogenic therapy withdrawal.
Sounni, Nor Eddine ULg; Cimino, Jonathan ULg; BLACHER, Silvia ULg et al

in Cell Metabolism (2014), 20(2), 280-94

The molecular mechanisms responsible for the failure of antiangiogenic therapies and how tumors adapt to these therapies are unclear. Here, we applied transcriptomic, proteomic, and metabolomic approaches ... [more ▼]

The molecular mechanisms responsible for the failure of antiangiogenic therapies and how tumors adapt to these therapies are unclear. Here, we applied transcriptomic, proteomic, and metabolomic approaches to preclinical models and provide evidence for tumor adaptation to vascular endothelial growth factor blockade through a metabolic shift toward carbohydrate and lipid metabolism in tumors. During sunitinib or sorafenib treatment, tumor growth was inhibited and tumors were hypoxic and glycolytic. In sharp contrast, treatment withdrawal led to tumor regrowth, angiogenesis restoration, moderate lactate production, and enhanced lipid synthesis. This metabolic shift was associated with a drastic increase in metastatic dissemination. Interestingly, pharmacological lipogenesis inhibition with orlistat or fatty acid synthase downregulation with shRNA inhibited tumor regrowth and metastases after sunitinib treatment withdrawal. Our data shed light on metabolic alterations that result in cancer adaptation to antiangiogenic treatments and identify key molecules involved in lipid metabolism as putative therapeutic targets. [less ▲]

Detailed reference viewed: 90 (31 ULg)
See detailHDAC5 depletion Decreases NDUFB5 Subunit of Mitochondrial Complex- I leading to Glucose-dependent Metabolic Reprogrammation
Hendrick, Elodie ULg; Matheus, Nicolas ULg; Peixoto, Paul ULg et al

Poster (2013, December 05)

Introduction : Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure ... [more ▼]

Introduction : Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1. Aims : The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Methods and results : Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of NDUFB5, a subunit of the complex I of the mitochondrial respiratory chain through modulation of mRNA stability. HDAC5 depletion-induced NDUFB5 downregulation causes a significant increase of ROS production and induces uncoupled mitochondrial respiration. In addition, this HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glucose. Indeed, interference with glucose supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Conclusions : Our study demonstrated for the first time that specific HDAC5 inhibition induces alteration of NDUFB5 gene expression by altering mRNA stability and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. [less ▲]

Detailed reference viewed: 6 (0 ULg)
See detailAge-related Macular Degeneration Study: A Metabolomics Approach
LAMBERT, Vincent ULg; De Tullio, Pascal ULg; Hansen, Sylvain ULg

Conference (2013, October 04)

Age-related macular degeneration (AMD) is a leading cause of vision loss in the western world among people aged 50 or older. 90% of all vision loss due to AMD result from the exudative form, which is ... [more ▼]

Age-related macular degeneration (AMD) is a leading cause of vision loss in the western world among people aged 50 or older. 90% of all vision loss due to AMD result from the exudative form, which is characterized by choroidal neovascularization (CNV). Age-related changes that induce pathologic CNV are incompletely understood. A successful application of anti-VEGF approaches in the clinic is obviously a turning point in AMD treatment. Nevertheless, despite such important advances, critical issues remain to be addressed. To better understand the etiology of this pathology, we have used and improved a model of laser-induced murine choroidal neovascularization. As none is known about the metabolic changes in patients with AMD, we decided to apply a 1H NMR metabolomics approach on AMD patients and on a mice CNV experimental model. This technique is a relatively new branch of « omics » technologies focused on the analysis and measurement of endogenous metabolites. These experiments provide unique challenges to fulfill the goal of improving the current status of physiological information related to metabolome and in general to functional genomics. For this purpose, sera from control and AMD patients, induced and non-induced mice have been collected and the metabolic profiles of these samples were determined by 1H NMR. After post-processing treatments, the different spectra were analyzed by statistical discriminant methodologies (PCA, ICA, PLS-DA). This approach allows the differentiation between control and AMD patients and between laser-induced mice and the control mice group. Moreover, the same discriminating spectral zones, lactate and lipoproteins profil, have been identified in human and mice model, leading to the emergence of different putative biomarkers. In mice model of laser-induced CNV, normalization of circulating lactate by dichloroacetate, decreases CNV development. These first interesting results open new way in the study of the AMD etiology and validate the use of 1H NMR and CNV model for the understanding of Age-related Macular Degeneration. [less ▲]

Detailed reference viewed: 15 (0 ULg)
Full Text
Peer Reviewed
See detailDevelopment of Thiophenic Analogues of Benzothiadiazine Dioxides as New Powerful Potentiators of 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid (AMPA) Receptors
Francotte, Pierre ULg; Goffin, Eric ULg; Fraikin, Pierre et al

in Journal of Medicinal Chemistry (2013), 56(20), 7838-7850

On the basis of the results obtained in previous series of AMPA potentiators belonging to 3,4-dihydro-2H-benzo- and 3,4-dihydro-2H-pyrido-1,2,4-thiadiazine 1,1-dioxides, the present work focuses on the ... [more ▼]

On the basis of the results obtained in previous series of AMPA potentiators belonging to 3,4-dihydro-2H-benzo- and 3,4-dihydro-2H-pyrido-1,2,4-thiadiazine 1,1-dioxides, the present work focuses on the design of original isosteric 3,4-dihydro-2H-thieno-1,2,4-thiadiazine 1,1-dioxides. Owing to the sulfur position, three series of compounds were developed and their activity as AMPA potentiators was characterized. In each of the developed series, potent compounds were discovered. After screening the selected active compounds on a safety in vivo test, 6-chloro-4-ethyl-3,4-dihydro-2H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide (24) appeared as the most promising compound and was further evaluated. Its effects on long-term potentiation in vivo and on AMPA-mediated noradrenaline release were measured to predict its potential cognitive enhancing properties. Finally, an object recognition test performed in mice revealed that 24 was able to significantly enhance cognition, after oral administration, at doses as low as 0.3 mg/kg. This study validates the interest of the isosteric replacement of the benzene or pyridine nuclei by the thiophene nucleus in the ring-fused thiadiazine dioxides class of AMPA potentiators. [less ▲]

Detailed reference viewed: 29 (7 ULg)
See detailComplexe I mitochondrial dysfunction in HDAC5 depleted cancer cells induces glucose-dependent metabolic reprogrammation.
Hendrick, Elodie ULg; Matheus, Nicolas ULg; Peixoto, Paul ULg et al

Poster (2013, September 13)

Introduction: Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure ... [more ▼]

Introduction: Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1. Aims: The goal of this study is to further understand the metabolic response of cancer cells to HDAC5 depletion. Results: Screening transcriptomic study demonstrated that HDAC5 depletion induces a deregulation of genes encoding subunits of complex I of the mitochondrial respiratory chain leading to a significant increase of ROS production and inducing uncoupled mitochondrial respiration. In addition, this HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glucose. Indeed, interference with glucose supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Conclusion: Our study demonstrated for the first time that specific HDAC5 inhibition induces alteration of gene expression encoding mitochondrial proteins in cancer cells and provide insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. elodie.hendrick@student.ulg.ac.be [less ▲]

Detailed reference viewed: 7 (0 ULg)
Full Text
Peer Reviewed
See detailEffect of head-to-head addition in vinyl acetate controlled radical polymerization: why is Co(acac)2-mediated polymerization so much better?
Morin, Aurélie N.; Detrembleur, Christophe ULg; Jérôme, Christine ULg et al

in Macromolecules (2013), 46(11), 4303-4312

The controlled polymerization of vinyl acetate has been recently achieved by several techniques, but PVAc with targeted Mn and low dispersity up to very high monomer conversions and high degrees of ... [more ▼]

The controlled polymerization of vinyl acetate has been recently achieved by several techniques, but PVAc with targeted Mn and low dispersity up to very high monomer conversions and high degrees of polymerization was only obtained with Co(acac)2 as controlling agent in the so-called CMRP, a type of organometallic mediated radical polymerization (OMRP). Other techniques (including ATRP, ITP, TERP, and RAFT/MADIX) have shown a more or less pronounced slowdown in the polymerization kinetics, which was attributed to the higher strength of the C−X bond between the radical PVAc chain and the trapping agent (X) in the dormant species and to a consequent slower reactivation after a less frequent head-to-head monomer addition. The reason for the CMRP exception is clarified by the present contribution. First, a detailed investigation by 1H, 13C and multiplicity-edited HSQC and DEPT-135 NMR of the PVAc obtained by CMRP, in comparison with a regular polymer made by free radical polymerization under the same conditions, has revealed that Co(acac)2 does not significantly alter the fraction of head-to-head sequences in the polymer backbone and that there is no accumulation of Co(acac)2-capped chains with a head-to-head ω end. Hence, both dormant chains (following the head-to-head and the head-to-tail monomer additions) must be reactivated at similar rates. A DFT study shows that this is possible because the dormant chains are stabilized not only by the C−Co σ bond but also by formation of a chelate ring through coordination of the ω monomer carbonyl group. The head-to-head dormant chain contains an inherently stronger C−Co bond but forms a weaker 6-membered chelate ring, whereas the weaker C−Co bond in the head-to-tail dormant chain is compensated by a stronger 5-membered chelate ring. Combination of the two effects leads to similar activation enthalpies, as verified by DFT calculations using a variety of local, gradient-corrected, hybrid and “ad hoc” functionals (BPW91, B3PW91, BPW91*, M06 and M06L). While the BDE(C−X) of model H-VAc−X molecules [X = Cl, I, MeTe, EtOC(S)S and Co(acac)2] are functional dependent, the BDE difference between head-to-head and head-to-tail dormant chain models is almost functional insensitive, with values of 5−9 kcal/mol for the ATRP, ITP and TERP models, 3−6 for the RAFT/MADIX model, and around zero for CMRP. [less ▲]

Detailed reference viewed: 27 (8 ULg)