The preparation of a wide variety of unique polymer brush structures can be accomplished
by “living” free radical polymerization of vinyl monomers from surface-tethered alkoxyamines or from
tethered α-halo esters in the presence of (PPh3)2NiBr2. The use of a “living” free radical process permits
the molecular weight and polydispersity of the covalently attached polymer chains to be accurately
controlled while also allowing the formation of block copolymers by the sequential growth of monomers
from the surface. These block and random copolymer brushes have been used to control surface properties.
1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD), N-methyl-TBD (MTBD), and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) are effective organocatalysts for the ring-opening polymerization (ROP) of cyclic esters
such as lactide (LA), δ-valerolactone (VL), and ε-caprolactone (CL). TBD is shown to polymerize LA, VL, and
CL in a fast and controlled manner, whereas MTBD and DBU polymerized LA and addition of a thiourea cocatalyst
led to the ROP of VL and CL being achieved. Each of the catalysts produced polymers displaying high end
group fidelity, good correlation between theoretical and observed molecular weight, and linear relationships between
conversion and molecular weight. The enhanced activity of TBD relative to MTBD and DBU is attributed to its
bifunctionality, enabling the simultaneous activation of both the cyclic ester monomer and the alcohol group of
the initiator/propagating species. Temperature-dependent NMR studies generated individual association constants
for MTBD with benzyl alcohol and thiourea with VL. In combination with temperature-dependent ROP of VL
in the presence of benzyl alcohol, MTBD, and thiourea, these data have led to the derivation of the activation
energy for the ROP (49 ± 3 kJ mol-1). The simplicity of the reaction conditions, the ready availability of the
catalysts, the variety of polymerizable cyclic ester monomers, and the exquisite control over the polymerization
are demonstrated.
Macromolecular antimicrobial agents such as cationic polymers and peptides have recently been under an increased level of scrutiny because they can combat multi-drug-resistant microbes. Most of these polymers are non-biodegradable and are designed to mimic the facially amphiphilic structure of peptides so that they may form a secondary structure on interaction with negatively charged microbial membranes. The resulting secondary structure can insert into and disintegrate the cell membrane after recruiting additional polymer molecules. Here, we report the first biodegradable and in vivo applicable antimicrobial polymer nanoparticles synthesized by metal-free organocatalytic ring-opening polymerization of functional cyclic carbonate. We demonstrate that the nanoparticles disrupt microbial walls/membranes selectively and efficiently, thus inhibiting the growth of Gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and fungi, without inducing significant haemolysis over a wide range of concentrations. These biodegradable nanoparticles, which can be synthesized in large quantities and at low cost, are promising as antimicrobial drugs, and can be used to treat various infectious diseases such as MRSA-associated infections, which are often linked with high mortality.
We report the use of atom transfer radical polymerization (ATRP) to amplify initiators
patterned on films of gold into polymer brushes of poly(methyl methacrylate) (PMMA), poly(hydroxyethyl
methacrylate) (PHEMMA), poly(tert-butyl methacrylate) (PTBA), poly(isobornyl methacrylate) (PIBMA),
and poly((dimethylamino)ethylmethyl acrylate) (PDMAEMA). Pattern transfer into gold substrates
underlying polymer brushes was achieved by using the patterned brushes as barriers to wet chemical
etchants of gold. The surface-confined initiators for ATRP were prepared by the self-assembly of (BrC(CH3)2COO(CH2) 10S)2 (I) on films of gold. These monolayers were assembled from solutions of hexadecane
at 60 °C so as to prevent their thermal desorption during ATRP (also performed at 60 °C). By measuring
the resistance offered by these brushes to etching of underlying films of gold by aqueous solutions of
KI/I2, KCN/K3Fe(CN)6, and 50 vol % aqua regia (70 vol % HNO3 and 30 vol % HCl), we conclude that
both the thickness and chemical functionality of the polymer brushes as well as the choice of etchant can
be tailored to control the etch resistance of polymer brushes. Thick brushes formed from hydrophobic
monomers were found to be the most effective in resisting all etchants. The etch resistance of a PMMA
brush was observed to be greatest when using aqua regia or KI/I2 to etch an underlying film of gold. For
example, when using PMMA brushes (thickness 450 Å), we measured the brushes to slow the etching of
the underlying films of gold by KI/I2 by almost 2 orders of magnitude as compared to monolayers formed
from I. By using microcontact printing to pattern SAMs formed from I, we demonstrate the usefulness
of ATRP in schemes for transferring patterns present in monolayers of molecules into underlying
substrates.
For patterning organic resists, optical and electron beam lithography are the most established methods; however, at resolutions below 30 nanometers, inherent problems result from unwanted exposure of the resist in nearby areas. We present a scanning probe lithography method based on the local desorption of a glassy organic resist by a heatable probe. We demonstrate patterning at a half pitch down to 15 nanometers without proximity corrections and with throughputs approaching those of Gaussian electron beam lithography at similar resolution. These patterns can be transferred to other substrates, and material can be removed in successive steps in order to fabricate complex three-dimensional structures.
Polymyxins remain the last line treatment for multidrug-resistant (MDR) infections. As polymyxins resistance emerges, there is an urgent need to develop effective antimicrobial agents capable of mitigating MDR. Here, we report biodegradable guanidinium-functionalized polycarbonates with a distinctive mechanism that does not induce drug resistance. Unlike conventional antibiotics, repeated use of the polymers does not lead to drug resistance. Transcriptomic analysis of bacteria further supports development of resistance to antibiotics but not to the macromolecules after 30 treatments. Importantly, high in vivo treatment efficacy of the macromolecules is achieved in MDR A. baumannii-, E. coli-, K. pneumoniae-, methicillin-resistant S. aureus-, cecal ligation and puncture-induced polymicrobial peritonitis, and P. aeruginosa lung infection mouse models while remaining non-toxic (e.g., therapeutic index—ED50/LD50: 1473 for A. baumannii infection). These biodegradable synthetic macromolecules have been demonstrated to have broad spectrum in vivo antimicrobial activity, and have excellent potential as systemic antimicrobials against MDR infections.
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