“Head‐to‐Middle” and “Head‐to‐Tail” cis‐Prenyl Transferases: Structure of Isosesquilavandulyl Diphosphate Synthase

We report the first X‐ray crystallographic structure of the “head‐to‐middle” prenyltransferase, isosesquilavandulyl diphosphate synthase, involved in biosynthesis of the merochlorin class of antibiotics. The protein adopts the ζ or cis‐prenyl transferase fold but remarkably, unlike tuberculosinol adenosine synthase and other cis‐prenyl transferases (e.g. cis‐farnesyl, decaprenyl, undecaprenyl diphosphate synthases), the large, hydrophobic side chain does not occupy a central hydrophobic tunnel. Instead, it occupies a surface pocket oriented at 90° to the hydrophobic tunnel. Product chain‐length control is achieved by squeezing out the ligand from the conventional allylic S1 binding site, with proton abstraction being achieved using a diphosphate‐Asn‐Ser relay. The structures revise and unify our thinking as to the mechanism of action of many other prenyl transferases and may also be of use in engineering new merochlorin‐class antibiotics.     

Structure and Function of a “Head‐to‐Middle” Prenyltransferase: Lavandulyl Diphosphate Synthase

We report the first X‐ray structure of the unique “head‐to‐middle” monoterpene synthase, lavandulyl diphosphate synthase (LPPS). LPPS catalyzes the condensation of two molecules of dimethylallyl diphosphate (DMAPP) to form lavandulyl diphosphate, a precursor to the fragrance lavandulol. The structure is similar to that of the bacterial cis‐prenyl synthase, undecaprenyl diphosphate synthase (UPPS), and contains an allylic site (S1) in which DMAPP ionizes and a second site (S2) which houses the DMAPP nucleophile. Both S‐thiolo‐dimethylallyl diphosphate and S‐thiolo‐isopentenyl diphosphate bind intact to S2, but are cleaved to (thio)diphosphate, in S1. His78 (Asn in UPPS) is essential for catalysis and is proposed to facilitate diphosphate release in S1, while the P1 phosphate in S2 abstracts a proton from the lavandulyl carbocation to form the LPP product. The results are of interest since they provide the first structure and structure‐based mechanism of this unusual prenyl synthase.     

Mediating Gel Formation from Structurally Controlled Poly(Electrolytes) Through Multiple “Head‐to‐Body” Electrostatic Interactions

Tuning the chain‐end functionality of a short‐chain cationic homopolymer, owing to the nature of the initiator used in the atom transfer radical polymerization (ATRP) polymerization step, can be used to mediate the formation of a gel of this poly(electrolyte) in water. While a neutral end group gives a solution of low viscosity, a highly homogeneous gel is obtained with a phosphonate anionic moiety, as characterized by rheometry and diffusion nuclear magnetic resonance (NMR). This novel type of supramolecular control over poly(electrolytic) gel formation could find potential use in a variety of applications in the field of electro‐active materials.

     

Polymer Brushes by the “Grafting to” Method

This paper focuses on the attachment of densely grafted polymer layers (polymer brushes) to various inorganic and polymeric substrates by the “grafting to” method. A brief overview of synthesis of polymer brushes by the method is first provided, with emphasis on chemical approaches to polymer attachment. The second part of the paper covers the synthesis of polymer layers via a recently developed macromolecular anchoring layer approach. Several examples of application of the grafting technique are presented for generation of hydrophobic, hydrophilic, gradient, and switchable surfaces.

     

Thermoresponsive Dendronized Polyprolines via the “Grafting to” Route

The first and second generations of dendronized polyprolines P3G1 , P3G2, and P4G1 are prepared via the “grafting to” route, and their thermoresponsive properties and helical conformations investigated. High molar masses of polyproline main chains carrying azido groups are achieved first by polycondensation of peptide precursors through activated ester strategy. Oligoethylene glycol dendrons cored with alkyne are then attached onto the main chains through click reaction. These polymers are found to be thermoresponsive. Circular dichroism spectroscopy investigation indicates, in contrast to P3G2 and P4G1 which adopt the expected PPII conformation in aqueous conditions, P3G1 prefers to adopt PPI helical conformation, and this conformation is stable within the measured time period and temperature range.

     

“Dumbbell”‐ and “Clackers”‐Shaped Dimeric Derivatives of Monocarba‐closo‐dodecaborate

We designed, synthesized, and characterized two types of dimeric forms of monocarba‐closo‐dodecaborate, namely, a “dumbbell”‐shaped dianion having a C?C bond and a “clackers”‐shaped monoanion having an iodonium linker. The unique architectures of these anionic molecules were established by X‐ray analysis. Spectroscopic analysis, DFT calculations, and reactivity experiments revealed high anionic and chemical stability of both anions, which are crucial properties for weakly coordinating anions.     

Atomistic Simulations of COSAN: Amphiphiles without a Head‐and‐Tail Design Display “Head and Tail” Surfactant Behavior

Cobaltabisdicarbollide (COSAN) anions have an unexpectedly rich self‐assembly behavior, which can lead to vesicles and micelles without having a classical surfactant molecular architecture. This was rationalized by the introduction of new terminology and novel driving forces. A key aspect in the interpretation of COSAN behavior is the assumption that the most stable form of these ions is the transoid rotamer, which lacks a “hydrophilic head” and a “hydrophobic tail”. Using implicit solvent DFT calculations and MD simulations we show that in water, 1) the cisoid rotamer is the most stable form of COSAN and 2) this cisoid rotamer has a well‐defined hydrophilic polar region (“head”) and a hydrophobic apolar region (“tail”). In addition, our simulations show that the properties of this rotamer in water (interfacial affinity, micellization) match those expected for a classical surfactant. Therefore, we conclude that the experimental results for the COSAN ions can now be understood in terms of its amphiphilic molecular architecture.     

“Kick‐Starting” oxetane photopolymerizations

In the presence of small amounts of 2,2‐dialkyl‐, 2,2,3‐trialkyl‐, or 2,2,3,3‐tetraalkyl substituted epoxides such as isobutylene oxide, 1,2‐limonene oxide, and 2,2,3,3,‐tetramethyl oxirane, the photoinitiated cationic ring‐opening polymerizations of 3,3‐disubstituted oxetanes are dramatically accelerated. The acceleration affect was attributed to an increase in the rate of the initiation step of these latter monomers. Both mono‐ and disubstituted oxetane monomers are similarly accelerated by the above‐mentioned epoxides to give crosslinked network polymers. The potential for the use of such “kick‐started” systems in applications such as coatings, adhesives, printing inks, dental composites and in three‐dimensional imaging is discussed. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2934–2946