Drug-Loaded, Bivalent-Bottle-Brush Polymers by Graft-through ROMP

Graft through ring-opening metathesis polymerization (ROMP) using ruthenium N heterocyclic carbene catalysts has enabled the synthesis of bottle-brush polymers with unprecedented ease and control Here we report the first bivalent-brush polymers, these materials were prepared by graft through ROMP of drug-loaded poly(ethylene glycol) (PEG) based macromonomers (MMs) Anticancer drugs doxorubicin (DOX) and camptothecin (CT) were attached to a norbornene alkyne-PEG MM via a photocleavable linker ROMP of either or both drug loaded MMs generated brush homo and copolymers with low polydispersities and defined molecular weights. Release of free DOX and CT from these materials was initiated by exposure to 365 nm light All of the CT and DOX polymers were at least 10 fold more toxic to human cancer cells after photoinitiated drug release while a copolymer carrying both CT and DOX displayed 30-fold increased toxicity upon irradiation Graft through ROMP of drug loaded macromonomers provides a general method for the systematic study of structure function relationships for stimuli responsive polymers in biological systems

The Living ROMP of trans-Cyclooctene

The living ring-opening metathesis polymerization (ROMP) of trans-cyclooctene (tCO) was investigated. ROMP of tCO in the presence of PPh_3 in THF leads to the formation of narrowly dispersed polycyclooctene (PCO). The presence of PPh3 as an additive and the use of THF as a solvent were demonstrated to be necessary to suppress competing secondary metathesis processes in the ROMP of tCO. Under optimal conditions, narrowly dispersed PCO was achieved without high molecular weight contaminates. The PCO was then hydrogenated to form linear, narrowly dispersed polyethylene with a melting temperature of 139 °C. Protected, hydroxy-functionalized tCO was polymerized by this method to afford narrowly dispersed, hydroxylated PCO. Block copolymers containing polynorbornene and PCO or containing differentially functionalized PCO were also synthesized and hydrogenated to form block copolymers containing blocks of linear, narrowly dispersed polyethylene

Ru-Catalyzed, cis-Selective Living Ring-Opening Metathesis Polymerization of Various Monomers, Including a Dendronized Macromonomer, and Implications to Enhanced Shear Stability

An unsaturated polymer’s cis/trans-olefin content has a significant influence on its properties. For polymers obtained by ring-opening metathesis polymerization (ROMP), the cis/trans-olefin content can be tuned by using specific catalysts. However, cis-selective ROMP has suffered from narrow monomer scope and lack of control over the polymerization (giving polymers with broad molecular weight distributions and prohibiting the synthesis of block copolymers). Herein, we report the versatile cis-selective controlled living ROMP of various endo-tricyclo[4.2.2.0^(2,5)]deca-3,9-diene and various norbornene derivatives using a fast-initiating dithiolate-chelated Ru catalyst. Polymers with cis-olefin content as high as 99% could be obtained with high molecular weight (up to M_n of 105.1 kDa) and narrow dispersity (<1.4). The living nature of the polymerization was also exploited to prepare block copolymers with high cis-olefin content for the first time. Furthermore, owing to the successful control over the stereochemistry and narrow dispersity, we could compare cis- and trans-rich polynorbornene and found the former to have enhanced resistance to shear degradation

Indirect economic effects of a rail link along the afsluitdijk

New transport infrastructure has a myriad of short and long run effects. The effects on population and economic activity are most difficult to estimate. This paper introduces three different models to estimate the impacts of new infrastructure on labour supply and demand, and carefully explains how the interaction between the models and their outcomes should be handled. The methodology is applied to a proposal for a magnetic levitation rail system from Groningen across the Afsluitdijk to Schiphol. This benchmark it is then used to derive a qualitative assessment for different trajectories and slower type of new rail infrastructure all using the Afsluitdijk. Finally, this paper discusses the remarkable differences in the quantitative outcomes with a comparable Maglev proposal that does not use the Afsluitdijk but runs through the polders of the former Zuiderzee.

Efficient Synthesis of Narrowly Dispersed Brush Polymers via Living Ring-Opening Metathesis Polymerization of Macromonomers

Various macromonomers (MMs) were efficiently synthesized through the copper-catalyzed “click” coupling of a norbornene moiety to the chain end of poly(methylacrylate), poly(t-butylacrylate), and polystyrene that were prepared using atom transfer radical polymerization. Ring-opening metathesis polymerization (ROMP) of these MMs was carried out using the highly active, fast-initiating ruthenium catalyst (H_2IMes)(pyr)_2(Cl)_2RuCHPh in THF at room temperature. ROMP of MMs was found to be living with almost quantitative conversions (>90%) of MMs, producing brush polymers with very low polydispersity indices of 1.01−1.07 and high Mn’s of 200−2600 kDa. The efficient ROMP of such MMs provides facile access to a variety of brush polymers and overcomes previous difficulties in the controlled polymerization of MMs. Atomic force microscopy of the brush polymer products revealed extended, wormlike shapes as a result of significant steric repulsion of densely grafted side chains

Indirect economic effects of a rail link along the afsluitdijk

New transport infrastructure has a myriad of short and long run effects. The effects on population and economic activity are most difficult to estimate. This paper introduces three different models to estimate the impacts of new infrastructure on labour supply and demand, and carefully explains how the interaction between the models and their outcomes should be handled. The methodology is applied to a proposal for a magnetic levitation rail system from Groningen across the Afsluitdijk to Schiphol. This benchmark it is then used to derive a qualitative assessment for different trajectories and slower type of new rail infrastructure all using the Afsluitdijk. Finally, this paper discusses the remarkable differences in the quantitative outcomes with a comparable Maglev proposal that does not use the Afsluitdijk but runs through the polders of the former Zuiderzee.

A Life-Cycle Overlapping-Generations Model of the Small Open Economy

In this paper we construct an overlapping generations model for the small open economy incorporating a realistic description of the mortality process. With agedependent mortality, the typical life-cycle pattern of consumption and saving results from the maximizing behaviour of individual households. Our ?Blanchard-Yaari-Modigliani?model is used to analytically study a number of typical shocks affecting the small open economy, namely a balanced-budget public spending shock, a temporary Ricardian tax cut, and an interest rate shock. The demographic details matter a lot?both the impulse-response functions and the welfare profiles (associated with the different shocks) are critically affected by them. These demographic details furthermore do not wash out in the aggregate. The model is flexible and can be applied to a wide variety of theoretical and policy issues.

Business cycle indexes: does a heap of data help?

Business cycle indexes are used to get a timely and frequent description of the state of the economy and its likely development in the near future. This paper discusses two methods for constructing business cycle indexes, the traditional NBER method and a recently developed dynamic factor model, and compares these methods for the euro area. The results suggest that a reliable indicator can be constructed from a limited number of series that are selected using economic logic.

Monotelechelic Poly(oxa)norbornenes by Ring-Opening Metathesis Polymerization Using Direct End-Capping and Cross-Metathesis

Two different methodologies for the synthesis of monotelechelic poly(oxa)norbornenes prepared by living ring-opening metathesis polymerization (ROMP) are presented. The first method, termed direct end-capping, is carried out by adding an internal cis-olefin terminating agent (TA) to the reaction mixture immediately after the completion of the living ROMP reaction. The second method relies on cross-metathesis (CM) between a methylene-terminated poly(oxa)norbornene and a cis-olefin TA mediated by the ruthenium olefin metathesis catalyst (H_(2)IMes)(Cl)_(2)Ru(CH-o-OiPrC_(6)H_4) (H_(2)IMes = 1,3-dimesitylimidazolidine-2-ylidene). TAs containing various functional groups, including alcohols, acetates, bromides, α-bromoesters, thioacetates, N-hydroxysuccinimidyl esters, and Boc-amines, as well as fluorescein and biotin groups, were synthesized and tested. The direct end-capping method typically resulted in >90% end-functionalization efficiency, while the CM method was nearly as effective for TAs without polar functional groups or significant steric bulk. End-functionalization efficiency values were determined by ^(1)H NMR spectroscopy