ion phase that leads to an alkyl radical coordinated to the iron-hydroxo complex by a weak OH---C hydrogen bond, labeled as CI; (ii) an alkyl (or OH) rotation phase whereby the alkyl group achieves a favorable orientation for rebound; and (iii) a rebound phase that leads to C-O bond making and the ferric-alcohol complexes, 4,2P. The two profiles remain close in energy throughout the first two phases and then bifurcate. Whereas the HS state exhibits a significant barrier and a genuine TS for rebound, in the LS state, once the right orientation of the alkyl group is achieved, the LS rebound proceeds in a virtually barrier-free fashion to the alcohol. As such, alkane hydroxylation proceeds by TSR,70-72,120 in which the HS mechanism is truly stepwise with a finite lifetime for the radical intermediate, whereas the LS mechanism is effectively concerted with an ultrashort lifetime for the radical intermediate. Subsequent studies of ethane and camphor hydroxylation by the Yoshizawa group117,181-183 arrived at basically the same conclusion, that the mechanism is typified by TSR. The differences between the results of Shaik et al.130,173,177-180 and Yoshizawa et al.117,181-183 were rationalized recently71,72 and shown to arise owing to technical problems and the choice of the mercaptide ligand,117,181-183 which is a powerful electron donor and is too far from the representation of cysteine in the protein environment. The most recent study of camphor hydroxylation, which was done at a higher quality,117 converged to the picture reported by Shaik et al.130,173,177-180 and shows a stepwise HS process with a barrier of more than 3 kcal/mol for C-O bond formation by rebound of the camphoryl radical vis-à-vis an effectively concerted LS process for which this barrier is 0.7 kcal mol-1 and is the rotational barrier for reaching the rebound position. By referring to Figure 21, it is possible to rationalize the clock data of Newcomb in a simple manner. The apparent lifetimes are based on the assumption that there is a single state that leads to the reaction, such that the radical lifetime can be quantitated from the rate constant of free radical rearrangement and the ratio of rearranged to unrearranged alcohol product. However, in TSR, the rearranged (R) product is formed only/mainly on the HS surface, while the unrearranged (U) product is formed mainly on Figure 20. Formal descriptions of iron(III)-peroxo, iron(III)-hydroperoxo, and iron(V)-oxo species with indication of the negative charges. The roles “electrophile” or “nucleophile” are assigned according to the charge type. Reprinted with permission from ref 7. Copyright 2000 Springer-Verlag Heidelberg. 3964 Chemical Reviews, 2004, Vol. 104, No. 9 Meunier et al.

Mechanism of oxidation reactions catalyzed by cytochrome p450 enzymes.

Modern synthetic methods have revolutionized polymer chemistry through the development of new and powerful strategies for the controlled synthesis of complex polymer architectures. 1-5 Many of these developments were spawned by new classes of transition metal catalysts for the synthesis of new polyolefin microstructures, 5 the design of highly efficient families of “living” polymerization strategies for the synthesis of block, graft, and star polymers, 6-12 controlled methods for the synthesis of dendritic macromolecules, 3,13,14

Organocatalytic ring-opening polymerization.

Flow chemistry involves the use of channels or tubing to conduct a reaction in a continuous stream rather than in a flask Flow equipment provides chemists with unique control over reaction parameters enhancing reactivity or in some cases enabling new reactions This relatively young technology has received a remarkable amount of attention in the past decade with many reports on what can be done in flow Until recently, however, the question, “Should we do this in flow?” has merely been an afterthought This review introduces readers to the basic principles and fundamentals of flow chemistry and critically discusses recent flow chemistry accounts

The Hitchhiker's Guide to Flow Chemistry

Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function.

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An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering

2.3. [4 + 4] Cycloadditions 1058 2.4. Photocycloadditions of Aromatic Compounds 1058 2.4.1. Benzene Derivatives 1058 2.4.2. Condensed Aromatic Compounds 1060 3. Photochemical Rearrangements 1061 4. Cyclizations 1064 4.1. Pericyclizations 1064 4.2. Norrish−Yang Reaction 1066 5. Photochemical Extrusion of Small Molecules 1067 6. Photochemical Electron Transfer 1068 6.1. Photochemical Electron-Transfer Reactions with a Catalytic Sensitizer 1068

Photochemical Reactions as Key Steps in Organic Synthesis

Two bil lion peo ple are now ex posed to the risk of ma laria, more than 400 mil lions, WHO es ti mates, fall ill each year and be tween 1 and 3 mil lions die (most of them be ing Af ri can chil dren). Ma laria is the high est mor tal ity of any par a sitic dis ease and the third cause of death by in fec tion af ter tu ber cu lo sis and AIDS. These data are a low es ti mate. In fact, ob tain ing ac cu rate in for ma tion on the rate of mor tal ity and mor bid ity is not easy, since the symp toms of acute ma laria are sim i lar to those of many other acute in fec tious dis eases, and fa cil i ties for in ves ti ga tion of sus pect cases are not eas ily avail able, lead ing to an un der es ti ma tion of ma lar ial cases. 1 Four dif fer ent Plasmodium spe cies are re spon si ble for ma laria in man. Among them, P. malariae and P. ovale are uni ver sally sus cep ti ble to the cheap and well tol er ated drug chloroquine. P. vivax is widely ex tended and some cases of re sis tance ap peared, how ever it is not le thal. P. falciparum is re spon si ble for all the ma lig nant cases: se vere ma laria (ce re bral ma laria) is an encephalopathy that, even with a suit able treat ment, can lead to death in 2-3 days (10-30% of cases). This lat ter spe cies is also in volved in all main cases of drug re sis tant ma laria. 2,3 Ma laria is trans mit ted to man by the bite of an in fected fe male anophele mosquitoe. The par a site first in vades and de vel ops within hepatocytes, and then col o nizes eryth ro cytes where is achieved its asex ual mul ti pli ca tion (Scheme I). Within eryth ro cytes, Plasmodium di gests the main part of host he mo glo bin (20-80%), us ing the re leased amino-acids to build its own pro teins. The syn chro nous intraerythrocytic mat u ra tion of par a sites leads to the cell burst go ing to gether with fe ver ac cess and deap ane mia. At each red blood cell burst (each 48 h for P. falciparum), non ma ture par a sites called mero zo ites are re leased for fur ther erythrocytic rein vasion, and also ga meto cytes that will achieve the sex ual de vel op ment of the par a site within mos quito af ter re ab sorp tion by bit ing the in fected man. The con trol of ma laria largely de pends on drug ther a pies. Sev eral classes of drugs can be con sid ered ac cord ing to the tar get par a site stage.

Odile Dechy-Cabaret

Papers

Re cent Ad vances in Ma laria Che mo ther apy