Nucleic Acid-Binding Dyes as Versatile Photocatalysts for Atom-Transfer Radical Polymerization.

Nucleic acid-binding dyes (NuABDs) are fluorogenic probes that light up after binding to nucleic acids. Taking advantage of their fluorogenicity, NuABDs have been widely utilized in the fields of nanotechnology and biotechnology for diagnostic and analytical applications. We demonstrate the potential of NuABDs together with an appropriate nucleic acid scaffold as an intriguing photocatalyst for precisely controlled atom-transfer radical polymerization (ATRP). Additionally, we systematically investigated the thermodynamic and electrochemical properties of the dyes, providing insights into the mechanism that drives the photopolymerization. The versatility of the NuABD-based platform was also demonstrated through successful polymerizations using several NuABDs in conjunction with diverse nucleic acid scaffolds, such as G-quadruplex DNA or DNA nanoflowers. This study not only extends the horizons of controlled photopolymerization but also broadens opportunities for nucleic acid-based materials and technologies, including nucleic acid-polymer biohybrids and stimuli-responsive ATRP platforms.

Electrochemically Mediated Atom Transfer Radical Polymerization Driven by Alternating Current.

Alternating current (AC) and pulsed electrolysis are gaining traction in electro(organic) synthesis due to their advantageous characteristics. We employed AC electrolysis in electrochemically mediated Atom Transfer Radical Polymerization (eATRP) to facilitate the regeneration of the activator CuI complex on Cu0 electrodes. Additionally, Cu0 served as a slow supplemental activator and reducing agent (SARA ATRP), enabling the activation of alkyl halides and the regeneration of the CuI activator through a comproportionation reaction. We harnessed the distinct properties of Cu0 dual regeneration, both chemical and electrochemical, by employing sinusoidal, triangular, and square-wave AC electrolysis alongside some of the most active ATRP catalysts available. Compared to linear waveform (DC electrolysis) or SARA ATRP (without electrolysis), pulsed and AC electrolysis facilitated slightly faster and more controlled polymerizations of acrylates. The same AC electrolysis conditions could successfully polymerize eleven different monomers across different mediums, from water to bulk. Moreover, it proved effective across a spectrum of catalyst activity, from low-activity Cu/2,2-bipyridine to highly active Cu complexes with substituted tripodal amine ligands. Chain extension experiments confirmed the high chain-end fidelity of the produced polymers, yielding functional and high molecular-weight block copolymers. SEM analysis indicated the robustness of the Cu0 electrodes, sustaining at least 15 consecutive polymerizations.

Simple Iron Halides Enable Electrochemically Mediated ATRP in Nonpolar Media.

An electrochemically controlled atom transfer radical polymerization (eATRP) was successfully carried out with a minimal amount (ppm-level) of FeBr3 catalyst in a nonpolar solvent, specifically anisole. Traditionally, nonpolar media have been advantageous for Fe-based ATRP, but their low conductivity has hindered any electrochemical application. This study introduces the application of electrocatalytic methods in a highly nonpolar polymerization medium. Precise control over the polymerization was obtained by employing anhydrous anisole with only 400 ppm of FeBr3 and applying a negative overpotential of 0.3 V. Additionally, employing an undivided cell setup with two simple iron wire electrodes resulted in a significant 15-fold reduction in electrical resistance compared to traditional divided cell setups. This enabled the production of polymers with a dispersity of ≤1.2. Lastly, an examination of kinetic and thermodynamic aspects indicated that the ppm-level catalysis was facilitated by the high ATRP equilibrium constant of Fe catalysts in nonpolar environments.

Reactivity Prediction of Cu-Catalyzed Halogen Atom Transfer Reactions Using Data-Driven Techniques.

In catalysis, linear free energy relationships (LFERs) are commonly used to identify reaction descriptors that enable the prediction of outcomes and the design of more effective catalysts. Herein, LFERs are established for the reductive cleavage of the C(sp3)-X bond in alkyl halides (RX) by Cu complexes. This reaction represents the activation step in atom transfer radical polymerization and atom transfer radical addition/cyclization. The values of the activation rate constant, kact, for 107 Cu complex/RX couples in 5 different solvents spanning over 13 orders of magnitude were effectively interpolated by the equation: log kact = sC(I + C + S), where I, C, and S are, respectively, the initiator, catalyst, and solvent parameters, and sC is the catalyst-specific sensitivity parameter. Furthermore, each of these parameters was correlated to relevant descriptors, which included the bond dissociation free energy of RX and its Tolman cone angle θ, the electron affinity of X, the radical stabilization energy, the standard reduction potential of the Cu complex, the polarizability parameter π* of the solvent, and the distortion energy of the complex in its transition state. This set of descriptors establishes the fundamental properties of Cu complexes and RX that determine their reactivity and that need to be considered when designing novel systems for atom transfer radical reactions. Finally, a multivariate linear regression (MLR) approach was adopted to develop an objective model that surpassed the predictive capability of the LFER equation. Thus, the MLR model was employed to predict kact values for >2000 Cu complex/RX pairs.

Electrochemical Investigation of Iron-Catalyzed Atom Transfer Radical Polymerization.

Use of iron-based catalysts in atom transfer radical polymerization (ATRP) is very interesting because of the abundance of the metal and its biocompatibility. Although the mechanism of action is not well understood yet, iron halide salts are usually used as catalysts, often in the presence of nitrogen or phosphorous ligands (L). In this study, electrochemically mediated ATRP (eATRP) of methyl methacrylate (MMA) catalyzed by FeCl3, both in the absence and presence of additional ligands, was investigated in dimethylformamide. The electrochemical behavior of FeCl3 and FeCl3/L was deeply investigated showing the speciation of Fe(III) and Fe(II) and the role played by added ligands. It is shown that amine ligands form stable iron complexes, whereas phosphines act as reducing agents. eATRP of MMA catalyzed by FeCl3 was investigated in different conditions. In particular, the effects of temperature, catalyst concentration, catalyst-to-initiator ratio, halide ion excess and added ligands were investigated. In general, polymerization was moderately fast but difficult to control. Surprisingly, the best results were obtained with FeCl3 without any other ligand. Electrogenerated Fe(II) effectively activates the dormant chains but deactivation of the propagating radicals by Fe(III) species is less efficient, resulting in dispersity > 1.5, unless a high concentration of FeCl3 is used.

Atom Transfer Radical Polymerization: A Mechanistic Perspective.

Since its inception, atom transfer radical polymerization (ATRP) has seen continuous evolution in terms of the design of the catalyst and reaction conditions; today, it is one of the most useful techniques to prepare well-defined polymers as well as one of the most notable examples of catalysis in polymer chemistry. This Perspective highlights fundamental advances in the design of ATRP reactions and catalysts, focusing on the crucial role that mechanistic studies play in understanding, rationalizing, and predicting polymerization outcomes. A critical summary of traditional ATRP systems is provided first; we then focus on the most recent developments to improve catalyst selectivity, control polymerizations via external stimuli, and employ new photochemical or dual catalytic systems with an outlook to future research directions and open challenges.

Comparative performance of ex situ artificial solid electrolyte interphases for Li metal batteries with liquid electrolytes.

The design of artificial solid electrolyte interphases (ASEIs) that overcome the traditional instability of Li metal anodes can accelerate the deployment of high-energy Li metal batteries (LMBs). By building the ASEI ex situ, its structure and composition is finely tuned to obtain a coating layer that regulates Li electrodeposition, while containing morphology and volumetric changes at the electrode. This review analyzes the structure-performance relationship of several organic, inorganic, and hybrid materials used as ASEIs in academic and industrial research. The electrochemical performance of ASEI-coated electrodes in symmetric and full cells was compared to identify the ASEI and cell designs that enabled to approach practical targets for high-energy LMBs. The comparative performance and the examined relation between ASEI thickness and cell-level specific energy emphasize the necessity of employing testing conditions aligned with practical battery systems.

Effect of an Endurance and Strength Mixed Circuit Training on Regional Fat Thickness: The Quest for the "Spot Reduction".

Accumulation of adipose tissue in specific body areas is related to many physiological and hormonal variables. Spot reduction (SR) is a training protocol aimed to stimulate lipolysis locally, even though this training protocol has not been extensively studied in recent years. Thus, the present study sought to investigate the effect of a circuit-training SR on subcutaneous adipose tissue in healthy adults. METHODS: Fourteen volunteers were randomly assigned to spot reduction (SR) or to a traditional resistance training (RT) protocol. Body composition via bioimpedance analysis (BIA) and subcutaneous adipose tissue via skinfold and ultrasound were measured before and after eight weeks of training. RESULTS: SR significantly reduced body mass (p < 0.05) and subcutaneous abdominal adipose tissue (p < 0.05). CONCLUSIONS: circuit-training SR may be an efficient strategy to reduce in a localized manner abdominal subcutaneous fat tissue depot.

p-Substituted Tris(2-pyridylmethyl)amines as Ligands for Highly Active ATRP Catalysts: Facile Synthesis and Characterization.

A facile and efficient two-step synthesis of p-substituted tris(2-pyridylmethyl)amine (TPMA) ligands to form Cu complexes with the highest activity to date in atom transfer radical polymerization (ATRP) is presented. In the divergent synthesis, p-Cl substituents in tris(4-chloro-2-pyridylmethyl)amine (TPMA3Cl ) were replaced in one step and high yield by electron-donating cyclic amines (pyrrolidine (TPMAPYR ), piperidine (TPMAPIP ), and morpholine (TPMAMOR )) by nucleophilic aromatic substitution. The [CuII (TPMANR2 )Br]+ complexes exhibited larger energy gaps between frontier molecular orbitals and >0.2 V more negative reduction potentials than [CuII (TPMA)Br]+ , indicating >3 orders of magnitude higher ATRP activity. [CuI (TPMAPYR )]+ exhibited the highest reported activity for Br-capped acrylate chain ends in DMF, and moderate activity toward C-F bonds at room temperature. ATRP of n-butyl acrylate using only 10-25 part per million loadings of [CuII (TPMANR2 )Br]+ exhibited excellent control.

Atom Transfer Radical Polymerization of Acrylic and Methacrylic Acids: Preparation of Acidic Polymers with Various Architectures.

The preparation of poly(acrylic acid) (PAA) with tailored architecture and morphology is important for the design of advanced polymer materials. Cu-catalyzed atom transfer radical polymerization (ATRP) of AA is challenging due to the tendency of dormant chains to undergo an intramolecular lactonization reaction with consequent loss of chain-end functionalities, as previously reported for ATRP of methacrylic acid (MAA). In addition, AA can coordinate to the Cu catalyst. Moreover, the lower ATRP reactivity of AA relative to MAA enhances side reactions during polymerizations. These issues were overcome by adjusting the composition of the catalytic system, the polymerization setup, and the initiator nature. AA conversion >70-80% was obtained in 5 h, producing PAA with D ≈1.4. Multifunctional water-soluble initiators provided PAA and PMAA with telechelic and star-shaped architectures. Block copolymers of MAA and AA confirmed the retention of chain-end functionalities during ATRPs.

Axially Ligated Mesohemins as Bio-Mimicking Catalysts for Atom Transfer Radical Polymerization.

Copper is the most common metal catalyst used in atom transfer radical polymerization (ATRP), but iron is an excellent alternative due to its natural abundance and low toxicity compared to copper. In this work, two new iron-porphyrin-based catalysts inspired by naturally occurring proteins, such as horseradish peroxidase, hemoglobin, and cytochrome P450, were synthesized and tested for ATRP. Natural protein structures were mimicked by attaching imidazole or thioether groups to the porphyrin, leading to increased rates of polymerization, as well as providing polymers with low dispersity, even in the presence of ppm amounts of catalysts.

Growing Polymer Brushes from a Variety of Substrates under Ambient Conditions by Cu0-Mediated Surface-Initiated ATRP.

Cu0-mediated surface-initiated atom transfer radical polymerization (Cu0 SI-ATRP) is a highly versatile, oxygen-tolerant, and extremely controlled polymer-grafting technique that enables the modification of flat inorganic surfaces, as well as porous organic and polymeric supports of different compositions. Exploiting the intimate contact between a copper plate, acting as a source of catalyst and reducing agent, and an initiator-bearing support, Cu0 SI-ATRP enables the rapid growth of biopassive, lubricious brushes from large flat surfaces, as well as from various organic supports, including cellulose fibers and elastomers, using microliter volumes of reaction mixtures, and without the need for deoxygenation of reaction mixtures or an inert atmosphere. Thanks to a detailed analysis of its mechanism and the parameters governing the polymerization process, polymer brush growth by Cu0 SI-ATRP can be precisely modulated and adapted to be applied to morphologically and chemically different substrates, setting up the basis for translating SI-ATRP methods from academic studies into technologically relevant surface-modification approaches.

Mechanistically Guided Predictive Models for Ligand and Initiator Effects in Copper-Catalyzed Atom Transfer Radical Polymerization (Cu-ATRP).

Copper-catalyzed atom transfer radical polymerization (Cu-ATRP) is one of the most widely used controlled radical polymerization techniques. Notwithstanding the extensive mechanistic studies in the literature, the transition states of the activation/deactivation of the growing polymer chain, a key equilibrium in Cu-ATRP, have not been investigated computationally. Therefore, the understanding of the origin of ligand and initiator effects on the rates of activation/deactivation is still limited. Here, we present the first computational analysis of Cu-ATRP activation transition states to reveal factors that affect the rates of activation and deactivation. The Br atom transfer between the polymer chain and the Cu catalyst occurs through an unusual bent geometry that involves pronounced interactions between the polymer chain end and the ancillary ligand on the Cu catalyst. Therefore, the rates of activation/deactivation are determined by both the electronic properties of the Cu catalyst and the ligand-initiator steric repulsions. In addition, our calculations revealed the important role of ligand backbone flexibility on the activation. These theoretical analyses led to the identification of three chemically meaningful descriptors, namely HOMO energy of the catalyst ( EHOMO), percent buried volume ( Vbur%), and distortion energy of the catalyst (Δ Edist), to describe the electronic, steric, and flexibility effects on reactivity, respectively. A robust and simple predictive model for ligand effect on reactivity is thereby established by correlating these three descriptors with experimental activation rate constants using multivariate linear regression. Validation using a structurally diverse set of ligands revealed the average error is less than ±2 kcal/mol compared to the experimentally derived activation energies. The same approach was also applied to develop a predictive model for reactivity of different alkyl halide initiators using R-X bond dissociation energy (BDE) and Cu-X halogenophilicity as descriptors.

Reductive Termination of Cyanoisopropyl Radicals by Copper(I) Complexes and Proton Donors: Organometallic Intermediates or Coupled Proton-Electron Transfer?

Cyanoisopropyl radicals, generated thermally by the decomposition of azobis(isobutyronitrile) (AIBN), participate in reductive radical termination (RRT) under the combined effect of copper(I) complexes and proton donors (water, methanol, triethylammonium salts) in acetonitrile or benzene. The investigated copper complexes were formed in situ from [CuI(MeCN)4]+BF4- in CD3CN or CuIBr in C6D6 using tris[2-(dimethylamino)ethyl]amine (Me6TREN), tris(2-pyridylmethyl)amine (TPMA), and 2,2'-bipyridine (BIPY) ligands. Upon keeping all other conditions constants, the impact of RRT is much greater for the Me6TREN and TPMA systems than for the BIPY system. RRT scales with the proton donor acidity (Et3NH+ ≫ H2O > CH3OH), it is reduced by deuteration (H2O > D2O and CH3OH > CD3OD), and it is more efficient in C6D6 than in CD3CN. The collective evidence gathered in this study excludes the intervention of an outer-sphere proton-coupled electron transfer (OS-PCET), while an inner-sphere PCET (IS-PCET) cannot be excluded for coordinating proton donors (water and methanol). On the other hand, the strong impact of RRT for the noncoordinating Et3NH+ in CD3CN results from the formation of an intermediate CuI-radical adduct, suggested by DFT calculations to involve binding via the N atom to yield keteniminato [L/Cu-N═C═CMe2]+ derivatives with only partial spin delocalization onto the Cu atom.

Atom Transfer Radical Polymerization: Billion Times More Active Catalysts and New Initiation Systems.

Approaching 25 years since its invention, atom transfer radical polymerization (ATRP) is established as a powerful technique to prepare precisely defined polymeric materials. This perspective focuses on the relation between structure and activity of ATRP catalysts, and the consequent choice of the initiating system, which are paramount aspects to well-controlled polymerizations. The ATRP mechanism is discussed, including the effect of kinetic and thermodynamic parameters and side reactions affecting the catalyst. The coordination chemistry and activity of copper complexes used in ATRP are reviewed in chronological order, while emphasizing the structure-activity correlation. ATRP-initiating systems are described, from normal ATRP to low ppm Cu systems. Most recent advancements regarding dispersed media and oxygen-tolerant techniques are presented, as well as future opportunities that arise from progressively more active catalysts and deeper mechanistic understanding.

Redox-switchable atom transfer radical polymerization.

Temporal control in atom transfer radical polymerization (ATRP) relies on modulating the oxidation state of a copper catalyst, as polymer chains are activated by L/CuI and deactivated by L/CuII. (Re)generation of L/CuI activator has been achieved by applying a multitude of external stimuli. However, switching the Cu catalyst off by oxidizing to L/CuII through external chemical stimuli has not yet been investigated. A redox switchable ATRP was developed in which an oxidizing agent was used to oxidize L/CuI activator to L/CuII, thus halting the polymerization. A ferrocenium salt or oxygen were used to switch off the Cu catalyst, whereas ascorbic acid was used to switch the catalyst on by (re)generating L/CuI. The redox switches efficiently modulated the oxidation state of the catalyst without sacrificing control over polymerization.

Preparation of Well-Defined Polymers and DNA-Polymer Bioconjugates via Small-Volume eATRP in the Presence of Air.

An aqueous electrochemically mediated atom transfer radical polymerization (eATRP) was performed in a small volume solution (75 µL) deposited on a screen-printed electrode (SPE). The reaction was open to air, thanks to the use of glucose oxidase (GOx) as an oxygen scavenger. Well-defined poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA), poly(oligo(ethylene oxide) methyl ether methacrylate) (POEOMA), and corresponding DNA-polymer biohybrids were synthesized by the small-volume eATRP at room temperature. The reactions were simplified and polymerization rates increased by the application of the enzyme deoxygenating system and the compact electrochemical setup. Importantly, the volume of polymerization mixture was lowered to microliters, which not only decreases the cost for each reaction, but can also be potentially implemented in combinatorial chemistry and electrode-array configurations for high-throughput systems.

Atom Transfer Radical Polymerization Enabled by Sonochemically Labile Cu-carbonate Species.

Atom transfer radical polymerization (ATRP) has been previously mediated by ultrasound using a low concentration of copper complex in water (sono-ATRP) or by addition of piezoelectric materials in organic solvents (mechano-ATRP). However, these procedures proceeded slowly and yielded polymers contaminated by new chains initiated by hydroxyl radicals or by residual piezoelectrics. Unexpectedly, in the presence of sodium carbonate, rapid sono-ATRP of methyl acrylate in DMSO was achieved (80% conversion in <2 h) with excellent control of molecular weights and low dispersities (Mw/Mn < 1.2). The in situ formed CuII/L-CO3 complex in the the presence of ultrasound generated CuI/L species as activators for ATRP and carbonate radical anions. The latter were scavenged by DMSO that was oxidized to dimethyl sulfone. This simple and robust process employs low-intensity ultrasound, air-stable CuII/L catalysts, and carbonate or bicarbonate salts (washing soda or baking soda) to prepare well-defined polyacrylates.

Translating Surface-Initiated Atom Transfer Radical Polymerization into Technology: The Mechanism of Cu0-Mediated SI-ATRP under Environmental Conditions.

The exceptional features of Cu0-mediated surface-initiated atom transfer radical polymerization (Cu0 SI-ATRP), and its potential for implementation in technologically relevant surface functionalizations are demonstrated thanks to a comprehensive understanding of its mechanism. Cu0 SI-ATRP enables the synthesis of multifunctional polymer brushes with a remarkable degree of control, over extremely large areas and without the need for inert atmosphere or deoxygenation of monomer solutions. When a polymerization mixture is placed between a flat copper plate and an ATRP-initiator-functionalized substrate, the vertical distance between these two overlaying surfaces determines the tolerance of the grafting process toward the oxygen, while the composition of the polymerization solution emerges as the critical parameter regulating polymer-grafting kinetics. At very small distances between the copper plate and the initiating surfaces, the oxygen dissolved in the solution is rapidly consumed via oxidation of the metallic substrate. In the presence of ligand, copper species diffuse to the surface-immobilized initiators and trigger a rapid growth of polymer brushes. Concurrently, the presence and concentration of added CuII regulates the generation of CuI-based activators through comproportionation with Cu0. Hence, under oxygen-tolerant conditions, the extent of comproportionation, together with the solvent-dependent rate constant of activation (kact) of ATRP are the main determinants of the growth rate of polymer brushes.

Control of Dispersity and Grafting Density of Particle Brushes by Variation of ATRP Catalyst Concentration.

Silica particles with grafted poly(methyl methacrylate) brushes, SiO2-g-PMMA, were prepared via activator regeneration by electron transfer (ARGET) atom transfer radical polymerization (ATRP). The grafting density and dispersity of the polymer brushes was tuned by the initial ATRP catalyst concentration ([CuII/L]0). Sparsely grafted particle brushes, which also displayed an anisotropic string-like structure in TEM images, were obtained at very low catalyst concentrations, [CuII/L]0 < 1 ppm. The effect of the initial catalyst concentration on dispersity and initiation efficiency in the particle brush system was similar to that observed in the synthesis of linear PMMA homopolymers. The kinetic study revealed a transition from controlled radical polymerization to a less controlled process at low monomer conversion, when the [CuII/L]0 decreased below about 10 ppm.