Hakan Durmaz

Double click reaction strategies for polymer conjugation and post-functionalization of polymers

Double click reaction strategies, which are a combination of different type of click reactions, allow the preparation of polymers with various topologies and the post-functionalization of polymers, which cannot be easily achieved by using only one click reaction. The most studied click reaction combinations may be listed as the Cu(I) catalyzed azide-alkyne cycloaddition (CuAAC)–Diels–Alder, and the CuAAC–nitroxide radical coupling reactions for polymer–polymer conjugation and the CuAAC–Diels–Alder, or the CuAAC–thiol-ene reactions for post-modification of polymers.

An easy way to the preparation of multi-miktoarm star block copolymers via sequential double click reactions

As a new synthetic route, we here employed sequential double click reactions involving azide–alkyne and Diels–Alder reactions for the preparation of multi-miktoarm star block copolymers by using the arm-first approach.

Chemically Orthogonal Three‐Patch Microparticles

Compared to two-dimensional substrates, only a few methodologies exist for the spatially controlled decoration of three-dimensional objects, such as microparticles. Combining electrohydrodynamic co-jetting with synthetic polymer chemistry, we were able to create two- and three-patch microparticles displaying chemically orthogonal anchor groups on three distinct surface patches of the same particle. This approach takes advantage of a combination of novel chemically orthogonal polylactide-based polymers and their processing by electrohydrodynamic co-jetting to yield unprecedented multifunctional microparticles. Several micropatterned particles were fabricated displaying orthogonal click functionalities. Specifically, we demonstrate novel two- and three-patch particles. Multi-patch particles are highly sought after for their potential to present multiple distinct ligands in a directional manner. This work clearly establishes a viable route towards orthogonal reaction strategies on multivalent micropatterned particles.

Well-defined polyethylene-based graft terpolymers by combining nitroxide-mediated radical polymerization, polyhomologation and azide/alkyne “click” chemistry

Novel well-defined polyethylene-based graft terpolymers were synthesized via the “grafting onto” strategy by combining nitroxide-mediated radical polymerization (NMP), polyhomologation and copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) “click” chemistry. Three steps were involved in this approach: (i) synthesis of alkyne-terminated polyethylene-b-poly(e-caprolactone) (PE-b-PCL-alkyne) block copolymers (branches) by esterification of PE-b-PCL-OH with 4-pentynoic acid; the PE-b-PCL-OH was obtained by polyhomologation of dimethylsulfoxonium methylide to afford PE-OH, followed by ring opening polymerization of e-caprolactone using PE-OH as a macroinitiator, (ii) synthesis of random copolymers of styrene (St) and 4-chloromethylstyrene (4-CMS) with various CMS contents, by nitroxide-mediated radical copolymerization (NMP), and conversion of chloride to azide groups by reaction with sodium azide (NaN3) (backbone) and (iii) “click” linking reaction to afford the PE-based graft terpolymers. All intermediates and final products were characterized by high-temperature size exclusion chromatography (HT-SEC), Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy (1H NMR) and differential scanning calorimetry (DSC).

Selective and Reversible Binding of Thiol-Functionalized Biomolecules on Polymers Prepared via Chemical Vapor Deposition Polymerization

We use chemical vapor deposition polymerization to prepare a novel dibromomaleimide-functionalized polymer for selective and reversible binding of thiol-containing biomolecules on a broad range of substrates. We report the synthesis and CVD polymerization of 4-(3,4-dibromomaleimide)[2.2]paracyclophane to yield nanometer thick polymer coatings. Fourier transformed infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the chemical composition of the polymer coating. The reactivity of the polymer coating toward thiol-functionalized molecules was confirmed using fluorescent ligands. As a proof of concept, the binding and subsequent release of cysteine-modified peptides from the polymer coating were also demonstrated via sum frequency generation spectroscopy. This reactive polymer coating provides a flexible surface modification approach to selectively and reversibly bind biomolecules on a broad range of materials, which could open up new opportunities in many biomedical sensing and diagnostic applications where specific binding and release of target analytes are desired.

1,3-Dipolar and Diels–Alder cycloaddition reactions on polyester backbones possessing internal electron-deficient alkyne moieties

In this study we prepared a series of polyesters containing electron deficient internal alkyne units derived from acetylene dicarboxylic acid in the main backbone. Next, one of the polyesters was employed as a polymeric platform in copper free cycloaddition reactions like, Huisgen type 1,3-dipolar and Diels–Alder cycloaddition reactions in the presence of various dipoles and dienes, respectively. The 1,3-dipolar cycloaddition reactions were performed at mild temperatures (rt and 40 °C) in 1,4-dioxane for 16 h and had moderately high efficiencies (80–100%). However, the Diels–Alder cycloaddition reactions were carried out at higher temperatures (60 to 120 °C) in 1,4-dioxane for 16 h with reasonable efficiencies (45–97%). Moreover, the polyester was successfully used in one-pot 1,3-dipolar, sequential 1,3-dipolar/Diels–Alder, and sequential 1,3-dipolar cycloaddition/retro-Diels–Alder reactions.

Long-circulating Janus nanoparticles made by electrohydrodynamic co-jetting for systemic drug delivery applications

Abstract Background: Nanoparticles with controlled physical properties have been widely used for controlled release applications. In addition to shape, the anisotropic nature of the particles can be an important design criterion to ensure selective surface modification or independent release of combinations of drugs. Purpose: Electrohydrodynamic (EHD) co-jetting is used for the fabrication of uniform anisotropic nanoparticles with individual compartments and initial physicochemical and biological characterization is reported. Methods: EHD co-jetting is used to create nanoparticles, which are characterized at each stage with scanning electron microscopy (SEM), structured illumination microscopy (SIM), dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Surface immobilization techniques are used to incorporate polyethylene glycol (PEG) and I125 radiolabels into the nanoparticles. Particles are injected in mice and the particle distribution after 1, 4 and 24 hours is assessed. Results and discussion: Nanoparticles with an average diameter of 105.7 nm are prepared by EHD co-jetting. The particles contain functional chemical groups for further surface modification and radiolabeling. The density of PEG molecules attached to the surface of nanoparticles is determined to range between 0.02 and 6.04 ligands per square nanometer. A significant fraction of the nanoparticles (1.2% injected dose per mass of organ) circulates in the blood after 24 h. Conclusion: EHD co-jetting is a versatile method for the fabrication of nanoparticles for drug delivery. Circulation of the nanoparticles for 24 h is a pre-requisite for subsequent studies to explore defined targeting of the nanoparticles to a specific anatomic site.

Synthesis of Poly(vitamin C) through ADMET

l-Ascorbic acid, commonly known as vitamin C and one of the most important biological compounds, is converted to a α,ω-diene monomer and subsequently polymerized for the first time by acyclic diene metathesis. Various experimental conditions such as polymerization medium, catalyst type, temperature, and monomer/catalyst ratio are studied. The moderate molecular weight polymers are achieved when the polymerizations are conducted under bulk conditions employing the Grubbs first generation (G1) or Hoveyda-Grubbs second generation catalyst (HG-2). In the solution case, on the other hand, low molecular weight polymers are obtained regardless of the catalyst type. Moreover, when the catalyst performances are compared, it is found that G1 produces the higher molecular weight as well as higher yield polymers with respect to the HG-2.

Ultrafast and efficient aza- and thiol-Michael reactions on a polyester scaffold with internal electron deficient triple bonds

A polyester scaffold possessing electron deficient triple bonds in the main chain was prepared and utilized as a precursor for aza- and thiol-Michael addition reactions. A variety of primary and secondary amines as well as thiol compounds were utilized in the reactions. Very high efficiencies were found for all Michael addition reactions in a reasonably short time (2 min). While aza-Michael addition reactions do not require any catalysts, thiol-Michael addition reactions could be performed in the presence of a catalyst. After a detailed catalyst search, 1,4-diazabicyclo[2.2.2]octane (DABCO) was found to be the most efficient catalyst for thiol-Michael addition reactions. It is also observed that when amidine and guanidine bases were utilized for thiol-Michael addition reactions, a second thiol addition appreciably occurred on the remaining double bonds. Besides, for the first time, one-pot and one-step heterofunctionalization on the polyester was performed either solely by aza-Michael addition reactions employing three or four different secondary amines, or by a combination of aza- and thiol-Michael addition reactions.