Towards the rational design of new catalysts for organic transformations

2012-2013The main goal of this PhD thesis has been providing a computational support to the development of new or better performing catalysts, leading to the synthesis of new materials. In this context, it is worth remembering that catalysis is a topic of primary relevance in the academy as well as in the industry, due to the enormous impact of catalysis in every day life. In particular, within this PhD project, attention has focused on catalytic systems based on Nheterocyclic carbene (NHC) ligands, which have emerged as useful ligands in the last ten years. In the first part of this thesis, the development of new molecular descriptors for the quantification of steric and electronic effects in transition metal based catalysts has been pursued. The final goal of this approach consists in rationalizing the highly disorganized and chaotic catalytic space, to orientate experimental efforts towards possibly well performing catalysts, and away from the ineffective ones. This would allow to pursue a catalysis by design approach, in alternative to the “trial and error” classical approach. In particular, descriptors based on topographic steric maps have emerged as powerful tools that can be easily used and interpreted by the scientific community. A user friendly web server has been implemented in order to allow the scientific community to build steric maps for the systems of interest. The web server has already achieved great success with a number of visitors all around the world. In the second part of the thesis, attention was focused on developing and rationalizing new catalysts in strict collaboration with experimental groups. The systems investigated represent advanced application of N-heterocyclic carbenes as ligand in Ru-catalyzed olefin metathesis, Pd-catalyzed C-C cross coupling reactions, and as catalysts in the organopolymerization of polar olefins. The detailed mechanistic studies have offered a comprehensive understanding of the whole mechanisms, an achievement almost impossible to achieve with experimental techniques only. The studies described in this work demonstrated that computational techniques can be of enormous value to screen novel catalyst architectures more rapidly, and to obtain insights that could help in the design and experimental synthesis of novel and improved catalysts. [edited by author]XII n.s

Testing DFT ability to predict the stereoselectivity of group 4 metallocenes in propylene polymerization

In this study we have tested the ability of a standard DFT computational protocol to reproduce the experimentally obtained stereoselectivity of 26 different C2-symmetric zirconocene catalysts active in propylene polymerization. The catalysts were chosen for their relevance in metallocene catalyzed polymerization of propylene. To this end, primary insertion of both si- and re-propylene enantiofaces into the Zr-CH2-CH(CH3)2 bond was considered to simulate the growing chains step. The energy difference between these two transition states, ΔEre-si, was taken as a measure of the stereoselectivity (pentad: mmmm%) of different catalysts. The results clearly indicated that there was a good agreement between ΔEre-si and the mmmm% values, so that greater ΔEre-si could correspond to higher mmmm%. A model was fitted to the experimentally obtained mmmm% against theoretical ΔEre-si. The coefficient of determination (R2) of the resultant plot was 0.9793, which indicated a good accuracy of the model. Finally, to quantify the steric role of the studied ligands in the observed stereoselectivity, the analysis of the buried volume (VBur) and of the steric maps was performed for two representative complexes. The images revealed that a greater asymmetric localization of the %VBur around the metal center led to a higher mmmm% in the resultant polymer

Organocatalytic Conjugate-Addition Polymerization of Linear and Cyclic Acrylic Monomers by N-Heterocyclic Carbenes: Mechanisms of Chain Initiation, Propagation, and Termination

This contribution presents a full account of experimental and theoretical/computational investigations into the mechanisms of chain initiation, propagation, and termination of the recently discovered N-heterocyclic carbene (NHC)-mediated organocatalytic conjugate-addition polymerization of acrylic monomers. The current study specifically focuses on three commonly used NHCs of vastly different nucleophilicity, 1,3-di-tert-butylimidazolin-2-ylidene (ItBu), 1,3-dimesitylimidazolin-2-ylidene (IMes), and 1,3,4-triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene (TPT), and two representative acrylic monomers, the linear methyl methacrylate (MMA) and its cyclic analog, biomass-derived renewable γ-methyl-α-methylene-γ-butyrolactone (MMBL). For MMA, there exhibits an exquisite selectivity of the NHC structure for the three types of reactions it promotes: enamine formation (single-monomer addition) by IMes, dimerization (tail-to-tail) by TPT, and polymerization by ItBu. For MMBL, all three NHCs promote no dimerization but polymerization, with the polymerization activity being highly sensitive to the NHC structure and the solvent polarity. Thus, ItBu is the most active catalyst of the series and converts quantitatively 1000–3000 equiv of MMBL in 1 min or 10 000 equiv in 5 min at room temperature to MMBL-based bioplastics with a narrow range of molecular weights of Mn = 70–85 kg/mol, regardless of the [MMBL]/[ItBu] ratio employed. The ItBu-catalyzed MMBL polymerization reaches an exceptionally high turnover frequency up to 122 s–1 and a high initiator efficiency value up to 1600%. Unique chain-termination mechanisms have been revealed, accounting for the production of relative high-molecular-weight linear polymers and the catalytic nature of this NHC-mediated conjugate-addition polymerization. Computational studies have provided mechanistic insights into reactivity and selectivity between two competing pathways for each NHC-monomer zwitterionic adduct, namely enamine formation/dimerization through proton transfer vs polymerization through conjugate addition, and mapped out extensive energy profiles for chain initiation, propagation, and termination steps, thereby satisfactorily explaining the experimental observations

Lewis pair polymerization by classical and frustrated Lewis pairs: acid, base and monomer scope and polymerization mechanism

Classical and frustrated Lewis pairs (LPs) of the strong Lewis acid (LA) Al(C6F5)3 with several Lewis base (LB) classes have been found to exhibit exceptional activity in the Lewis pair polymerization (LPP) of conjugated polar alkenes such as methyl methacrylate (MMA) as well as renewable α-methylene- γ-butyrolactone (MBL) and γ-methyl-α-methylene-γ-butyrolactone (γ-MMBL), leading to high molecular weight polymers, often with narrow molecular weight distributions. This study has investigated a large number of LPs, consisting of 11 LAs as well as 10 achiral and 4 chiral LBs, for LPP of 12 monomers of several different types. Although some more common LAs can also be utilized for LPP, Al(C6F5)3-based LPs are far more active and effective than other LA-based LPs. On the other hand, several classes of LBs, when paired with Al(C6F5)3, can render highly active and effective LPP of MMA and γ-MMBL; such LBs include phosphines (e.g., PtBu3), chiral chelating diphosphines, N-heterocyclic carbenes (NHCs), and phosphazene superbases (e.g., P4-tBu). The P4-tBu/Al(C6F5)3 pair exhibits the highest activity of the LP series, with a remarkably high turn-over frequency of 9.6 × 104 h−1 (0.125 mol% catalyst, 100% MMA conversion in 30 s, Mn = 2.12 × 105 g mol−1, PDI = 1.34). The polymers produced by LPs at RT are typically atactic (PγMMBL with ∼47% mr) or syndio-rich (PMMAwith ∼70–75% rr), but highly syndiotactic PMMAwith rr ∼91% can be produced by chiral or achiral LPs at −78 °C. Mechanistic studies have identified and structurally characterized zwitterionic phosphonium and imidazolium enolaluminates as the active species of the current LPP system, which are formed by the reaction of the monomer·Al(C6F5)3 adduct with PtBu3 and NHC bases, respectively. Kinetic studies have revealed that the MMA polymerization by the tBu3P/Al(C6F5)3 pair is zero-order in monomer concentration after an initial induction period, and the polymerization is significantly catalyzed by the LA, thus pointing to a bimetallic, activated monomer propagation mechanism. Computational study on the active species formation as well as the chain initiation and propagation events involved in the LPP of MMAwith some of the most representative LPs has added our understanding of fundamental steps of LPP. The main difference between NHC and PR3 bases is in the energetics of zwitterion formation, with the NHC-based zwitterions being remarkably more stable than the PR3-based zwitterions. Comparison of the monometallic and bimetallic mechanism

Synthesis and reactivity of [Au(NHC)(Bpin)] complexes

The authors gratefully acknowledge the Royal Society (University Research Fellowship to C.S.J.C.), AstraZeneca (Studenship to C.M.Z) and VLAIO (CO2PERATE) for support of this work. We thank King Saud University (DSF Program) and KAUST (Award No.OSR-2015-CCF-1974-03) for support.A new class of [Au(NHC)(Bpin)] complexes has been synthesized and their unusual reactivity was investigated using computational and experimental methods. The gold-boryl complexes exhibit unexpected high stability and reactivity.PostprintPeer reviewe

A mechanistically and operationally simple route to metal-N-heterocyclic carbene (NHC) Complexes

We gratefully acknowledge VLAIO (SBO project CO2PERATE), King Saud University (Distinguished Scientist Fellowship Program) and King Abdullah University of Science and Technology for support. The Special Research Fund (BOF) of Ghent University is also acknowledged (Doctoral Scholarship to N.V.T.). COST action (CA15106-CHAOS) is thanked for mobility support to N.V.T. Umicore AG is acknowledged for generous gifts of materials.We have been puzzled by the involvement of weak organic and inorganic bases in the synthesis of metal‐N‐heterocyclic carbene (NHC) complexes. Such bases are insufficiently strong to permit the presumed required deprotonation of the azolium salt (the carbene precursor) prior to metal binding. Experimental and computational studies provide support for a base‐assisted concerted process that does not require free NHC formation. The synthetic protocol was found applicable to a number of Transition Metal‐ and Main Group‐centered NHC compounds and could become the synthetic route of choice to form M‐NHC bonds.PostprintPeer reviewe

CONTRIBUTION TO THE REVALUATION OF IVAN MEŠTROVIĆ ARCHITECTURAL LEGACY IN LIGHT OF MUSEOLOGICAL AND INHERITANCE CONSIDERATION

Arhitektonski opus Ivana Meštrovića u kontekstu vremena i prilika u kojima je umjetnik stvarao zasigurno je izniman doprinos hrvatskom graditeljstvu prve polovice 20. st. Njegova valorizacija višestruko je važna, osobito s muzeološkoga, stilskoga i programatskoga gledišta. U slojevitom eklekticizmu svih Meštrovićevih ostvarenih i neostvarenih arhitektonskih te urbanističkih projekata stilska raščlamba i diferencijacija svakoga pojedinog objekta i nacrta postavlja se kao nužna polazišna točka koju naknadno slijedi povijesnoumjetničko vrednovanje i muzeološke preferencije. Neosporno višejezičan vokabular Meštrovićevih arhitektonskih zamisli za sve je vrijeme njegova stvaralaštva pod kontinuiranim utjecajem različitih arhitektonskih rječnika u širokome vremenskom rasponu od starovjekovnih civilizacija do modernih tekovina. U umjetnikovu opusu mogu se posve jasno iščitati prostorne, tlocrtne, dispozicijske i pejzažne zadanosti klasičnoga arhitektonskog promišljanjaThe article analyzes the problem of the architectural legacy of Ivan Meštrović with the intention of seeing the importance of this under-examined area of his work. An analytical examination, scientific analysis and subsequent popularization of the architectural oeuvre of Ivan Meštrović and, in general, its contribution to the national and European architecture of the first half of the 20th century is important for a better scientific and museological evaluation of the architectural heritage. The architecture of Ivan Meštrović tends to be undervalued in comparison with his sculptural production. The research into and the systematic treatment and protection of the architectural monuments of this great artist can provide us with an insight into a new world of space, volume and shapes, and of design, conceptual and construction solutions. In the sea of dissimilarity, the models and various stylistic narrations reveal to us Meštrović the architect. The paper is structured in such a way that the first part refers to the artist’s education and the acquisition of basic architectural knowledge during his study in Vienna, helping him to form an architectural style of his own through the prism of the influences of various cultures and civilisations. In the second part the focus is directed at separate analysis and interpretation of designed and constructed buildings, as well as those whose ideas were not realized. Monuments are categorized into four groups according to theme and use: memorial buildings, religious buildings, creative and living spaces, public buildings. An analysis of Meštrović’s architecture reveals a pluralism of styles, within which several dominant sources stand out. Primarily these are classicism, then the medieval religious architecture of Dalmatia, Egyptian monumentalism and the influences of his many collaborators

Synthesis of gold(I)-trifluoromethyl complexes and their role in generating spectroscopic evidence for a gold(I)-difluorocarbene species

We thank the Ghent University (IoF), the Special Research Fund (BOF) starting (SPN, CSJC) and advanced (SPN, KVH) grants and Research Foundation Flanders (FWO) (fellowship to SVB and grant to CSJC and KVH) for funding.Readily-prepared and bench-stable [Au(CF3)(NHC)] compounds were synthesized using new methodologies, starting from [Au(OH)(NHC)], [Au(Cl)(NHC)] or [Au(L)(NHC)]HF2 precursors (NHC = N-heterocyclic carbene). The mechanism of formation of these species was investigated. Consequently, a new and straightforward strategy for the mild and selective cleavage of a single carbon-fluorine bond from [Au(CF3)(NHC)] complexes was attempted and found to be reversible in the presence of an additional nucleophilic fluoride source. This straightforward technique has led to the unprecedented spectroscopic observation of a gold(I)-NHC difluorocarbene species.PostprintPeer reviewe

A djuvant treatment in patients at high risk of recurrence of thymoma: Efficacy and safety of a three-dimensional conformal radiation therapy regimen

The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma. METHODS: Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44-60) Gy was delivered to the tumor bed by 6-20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter. RESULTS: Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered. CONCLUSION: Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma

A database solution for the quantitative characterisation and comparison of deep-marine siliciclastic depositional systems

In sedimentological investigations, the ability to conduct comparative analyses between deep-marine depositional systems is hindered by the wide variety in methods of data collection, scales of observation, resolution, classification approaches and terminology. A relational database, the Deep-Marine Architecture Knowledge Store (DMAKS), has been developed to facilitate such analyses, through the integration of deep-marine sedimentological data collated to a common standard. DMAKS hosts data on siliciclastic deep-marine system boundary conditions, and on architectural and facies properties, including spatial, temporal and hierarchical relationships between units at multiple scales. DMAKS has been devised to include original and literature-derived data from studies of the modern sea-floor, and from ancient successions studied in the sub-surface and in outcrop. The database can be used as a research tool in both pure and applied science, allowing the quantitative characterisation of deep-marine systems. The ability to synthesise data from several case studies and to filter outputs on multiple parameters that describe the depositional systems and their controlling factors enables evaluation of the degree to which certain controls affect sedimentary architectures, thereby testing the validity of existing models. In applied contexts, DMAKS aids the selection and application of geological analogues to hydrocarbon reservoirs, and permits the development of predictive models of reservoir characteristics that account for geological uncertainty. To demonstrate the breadth of research applications, example outputs are presented on: (i) the characterisation of channel geometries, (ii) the hierarchical organisation of channelised and terminal deposits, (iii) temporal trends in the deposition of terminal lobes, (iv) scaling relationships between adjacent channel and levee architectural elements, (v) quantification of the likely occurrence of elements of different types as a function of the lateral distance away from an element of known type, (vi) proportions and transition statistics of facies in elements and beds, (vii) variability in net-to-gross ratios among element types