Group Transfer Reactions Research Articles

Molecular dynamics study of waste tire pyrolysis: Focus on intermediate product evolution and sulfur migration law

With the rapid development of the automotive industry, the large number of waste tires poses significant environmental and health pressures. Pyrolysis technology offers a way to resourcefully utilize waste tires by converting them into pyrolysis oil, pyrolysis gas, and pyrolysis char, which has promising application prospects. However, there are still considerable challenges in the application of this technology, such as unclear reaction mechanisms and the high sulfur content of the products, which limit its practical implementation. Although some research has elucidated the pyrolysis mechanisms, there remain significant gaps in understanding the evolution paths of key intermediate and final products, as well as the detailed migration and transformation patterns of sulfur. This study uses reactive molecular dynamics simulation to investigate the pyrolysis process of tires. A three-dimensional polymer molecular model was constructed to study the pyrolysis process of waste tires at different temperatures, focusing on the evolution of key products, intermediate products, and sulfur-containing components. The results indicate that CH4 and ·CH3 radicals collide with unsaturated hydrocarbons through carbon-hydrogen transfer reactions and radical chain reactions, leading to polymerization. During the initial stage of pyrolysis, sulfur primarily exists in the form of sulfur-containing hydrocarbons (CHS). As pyrolysis progresses, the quantity of CHS decreases. With increasing pyrolysis temperature, the proportion of sulfur in the S form far exceeds that of CHS. At a pyrolysis temperature of 3000 K, the proportion of S is 64 %, while the proportion of CHS is 23 %.

Acyl Transfer Reactions of 2,4-Dinitrophenyl Furoates: Comparative Effects of Nucleophiles and Non-Leaving Groups

This study investigated the acyl group transfer reactions of 2,4-dinitrophenyl 5-substituted-2-furoates, promoted by 4-substituted phenoxides/phenols in a 20 mol% DMSO aqueous solution at 25 °C. The reactions yielded nucleophilic substitution products and displayed second-order kinetics, with βacyl values ranging from −2.24 to −2.50, ρ(x) values between 3.18 and 3.56, and βnuc values of 0.81 to 0.84. These findings indicate an addition–elimination mechanism where the initial step is rate-determining. Comparative analysis with previous data revealed that the transition state structure remained largely consistent when altering the non-leaving group from thienyl to furyl under similar conditions. Notably, a shift in the rate-determining step was observed when changing the nucleophile from secondary amines/ammonium ions to 4-substituted phenoxides/phenols, highlighting the significant impact of nucleophile selection on the reaction kinetics and mechanisms in acyl transfer reactions.

Sustainable methods for producing food-derived bioactive compounds

Background: Pursuing alternative starting materials has gained significant importance in the food and drug industries, driven by the global shift towards sustainable and renewable resources. Terpenes, naturally occurring hydrocarbons derived from plants, present a promising solution due to their abundant availability and range of physiological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer properties. Objective: This study aims to develop a waste-free synthesis methodology for functionalizing limonene and myrcene, two notable terpenes, through Atom Transfer Radical Reactions (ATRR). The objective is to achieve high yields and purities while enhancing the therapeutic potential of these compounds and adhering to green chemistry principles. Methods: A catalytic complex of Cu(I)Br and dimethyl sulfoxide (DMSO) was used to facilitate the coupling of limonene and myrcene with various trichloroacetic acid derivatives. Reactions were performed at 80°C for 90 minutes, and products were purified by column chromatography. The synthesized compounds were characterized using Gas Chromatography-Mass Spectrometry (GC-MS) and Nuclear Magnetic Resonance (NMR). Microbiological analyses were conducted using the disk-diffusion method, and statistical analyses were performed to assess the reliability of the experiments. Results: The ATRR methodology enabled the efficient functionalization of limonene and myrcene, achieving high yields and purities. The best yield for limonene was 70%, and for myrcene, 82%, both using trichloroacetonitrile. The Cu(I) catalytic system showed dualistic biological effects, with 3% concentration exhibiting strong bactericidal and fungicidal activity, while 0.03% promoted growth. These results demonstrate the potential of the methodology and the catalytic system for bioactive compound synthesis and agricultural applications. Conclusion: This study demonstrates the viability of ATRR for efficiently functionalizing limonene and myrcene, achieving high yields and purities. The synthesized compounds show promise for pharmaceutical development. The dual antibacterial and antifungal activities of the Cu(I) catalytic system also suggest potential applications in wastewater reutilization. Future work should explore the biological effects and environmental impact of this process. Keywords: Terpenes, ATR reactions, Green Chemistry, Bioactive compounds, Therapeutic potential.

Mechanism of Methyl Transfer Reaction between CH3Co(dmgBF2)2py and PPh3Ni(Triphos).

DFT calculations were performed for the methyl group transfer reaction between CH3Co (dmgBF2)py and PPh3Ni(Triphos). The reaction mechanism and its energetics were investigated. This reaction is relevant to the catalytic mechanism of the enzyme acetyl coenzyme A synthase. BP86 and PBE functionals and dispersion corrections were used. It was found that intermolecular interactions are very important for this reaction. The influence of the solvent on the reaction was studied.

Iron(I) Complex Bearing an Open-Shell Diazenido Ligand.

Low-valent transition-metal diazenido species are important intermediates in transition-metal-mediated dinitrogen reduction reactions. Isolable complexes of the type unanimously feature closed-shell diazenido ligands. Those bearing open-shell diazenido ligands have remained elusive. Herein, we report the synthesis, characterization, and reactivity of a d7 iron(I) complex featuring an open-shell silyldiazenido ligand, [(ICy)Fe(NNSiiPr3)(η2:η2-dvtms)] (1, ICy = 1,3-dicyclohexylimidazole-2-ylidene, dvtms = divinyltetramethyldisiloxane). Complex 1 is prepared in good yield by silylation of the iron(-I)-N2 complex [K(18-crown-6)][(ICy)Fe(N2)(η2:η2-dvtms)] with iPr3SiOTf and has been fully characterized by various spectroscopic methods. Theoretical studies, in combination with characterization data, established an S = 1/2 ground spin-state for 1 that can best be described as a quartet iron(I) center featuring an antiferromagnetically coupled triplet silyldiazenido ligand. The diazenido and alkene ligands in 1 are labile, as indicated by the facile disproportionation reaction of 1 at ambient temperature to transform into the iron(II) bis(diazenido) species [(ICy)(NNSiiPr3)2Fe(dvtms)Fe(NNSiiPr3)2(ICy)] (2) and the iron(0) species [(ICy)Fe(η2:η2-dvtms)] and also the alkene-exchange reaction of 1 with PhCH═CHBC8H14 to form [(ICy)Fe(NNSiiPr3)(η2-trans-PhCH═CHBC8H14)] (3). Complex 1 is light-sensitive. Upon photolysis, it undergoes a SiiPr3 radical-transfer reaction to yield [(ICy)Fe(σ:η2-MeCHSiMe2OSiMe2CH═CHSiiPr3)] (4) and N2. The reactions of 1 with the trityl radical and organic bromides yield iron(II) complexes, which indicates its reducing nature. Moreover, 1 is a weak hydrogen-atom abstractor, as indicated by its inertness toward HSi(SiMe3)3 and cyclohexa-1,4-diene and the low calculated N-H bond dissociation energy (48 kcal/mol) of its corresponding iron(II) iso-hydrazenido species.

Unveiling distinct influencing mechanisms of Br- on NDMA formation during ozonation of actual water Matrixes: Identification of precursors and brominated substance

Bromide ion (Br-) in water sources has been found to affect the formation of carcinogenic non-brominated N-nitrosodimethylamine (NDMA) during ozonation of typical amines. The increasing bromide levels bring more concern due to climate change and industrial discharge, but its effects on actual water matrixes were still unclear. In this study, NDMA formation from three actual water matrixes during ozonation as the Br- concentration increased from 0 to 100 µM were investigated (promotion (100.4 ∼ 231.6 ng/L), promotion then inhibition (399.5 ∼ 461.2 ∼ 428.2 ng/L), and subtle influence (51.9 ± 6.9 ng/L)); from which the NDMA precursors were screened and 8 precursors were selected for exploring the influencing mechanisms. The results indicated that the roles of Br- on NDMA formation significantly depended on the water characteristics of actual matrixes. A total of 16 typical NDMA precursors, which were mainly derived from industrial, agricultural and pharmaceutical sources, were identified. Moreover, 6 brominated substance (Br-DMA, Br-UDMH, Br-DMSC, Br-DMS, Br-TMDS, Br2-TMDS), which were thought to play a crucial role in promoting NDMA formation, were also identified in actual water by precursor ion scan (PIS) method. Hypobromous acid (HOBr), which has been proved to be the culprit to the generation of brominated substances, tend to attack the electron-donating groups of amines, such as acylamino (–NHCO-R) or amidogen (–NH2) groups. However, the reactive bromine species (∙Br and ∙Br2-) was inclined to attack the aromatic and anti-oxidant moieties then result in Br- release, as no bromine substitution but free radical transfer reaction occurs. Therefore, decreasing HOBr formation is the crucial step to reduce NDMA generation. This work would provide technical guide for NDMA risks control during ozonation of Br--amines co-containing water matrixes.

Cu(III)‐CF3 Compound‐Activated DMSO: An Efficient Oxidizing Reagent to Convert Alcohols to Ketones

AbstractIn this study high‐valent Cu(III) trifluoromethyl compounds in combination with DMSO is shown to be an efficient and mild oxidizing system for the conversion of alcohols to ketones (aldehydes as well). Trifluoromethoxylated sulfonium species is proposed to be initially formed that engages in crucial steps of alkoxy replacement at sulfonium center and deprotonative collapse of the resulting alkoxysulfonium intermediate in the presence of a base. This reaction is highly selective without over‐oxidation, and can tolerate a broad range of functional groups owing to mild oxidizing ability of the Cu(III)‐CF3/DMSO system and the inert N2 conditions. This method can be applied to the synthesis and functionalization of commercial drug compounds. This study illustrates an unusual reactivity property of high‐valent Cu(III) trifluoromethyl compounds beyond the conventional CF3 group transfer reactivity, and opens up new opportunities for developing novel reactions of Cu(III)‐CF3 compounds. The combined use of high‐valent Cu(III)‐CF3 compound and DMSO is anticipated to find more applications to develop other novel and useful oxidation reactions.

Universal inter-molecular radical transfer reactions on metal surfaces.

On-surface synthesis provides tools to prepare low-dimensional supramolecular structures. Traditionally, reactive radicals are a class of single-electron species, serving as exceptional electron-withdrawing groups. On metal surfaces, however, such species are affected by conduction band screening effects that may even quench their unpaired electron characteristics. As a result, radicals are expected to be less active, and reactions catalyzed by surface-stabilized radicals are rarely reported. Herein, we describe a class of inter-molecular radical transfer reactions on metal surfaces. With the assistance of aryl halide precursors, the coupling of terminal alkynes is steered from non-dehydrogenated to dehydrogenated products, resulting in alkynyl-Ag-alkynyl bonds. Dehalogenated molecules are fully passivated by detached hydrogen atoms. The reaction mechanism is unraveled by various surface-sensitive technologies and density functional theory calculations. Moreover, we reveal the universality of this mechanism on metal surfaces. Our studies enrich the on-surface synthesis toolbox and develop a pathway for producing low-dimensional organic materials.

Polyamine Inhibitor SAM486A Augments Cytarabine Cytotoxicity in Methylthioadenosine Phosphorylase-deficient Leukemia Cells.

Methionine metabolism contributes to supplying sulfur-containing amino acids, controlling the methyl group transfer reaction, and producing polyamines in cancer cells. Polyamines play important roles in various cellular functions. Methylthioadenosine phosphorylase (MTAP), the key enzyme of the methionine salvage pathway, is reported to be deficient in 15-62% of cases of hematological malignancies. MTAP-deficient cancer cells accumulate polyamines, resulting in enhanced cell proliferation. The aim of this study was to investigate the combined effects of the polyamine synthesis inhibitor SAM486A and the anticancer antimetabolite cytarabine in MTAP-deficient leukemic cells in vitro. The leukemia cell line U937 and the subline, U937/MTAP(-), in which MTAP was knocked down by shRNA, were used. The experiments were performed in media supplemented with 20% methionine (low methionine), which was the minimum concentration for maintaining cellular viability. The knockdown efficiency test confirmed a 70% suppression of the expression of the MTAP gene in U937/MTAP(-) cells. Even in the media with low methionine, the intracellular methionine concentration was not reduced in U937/MTAP(-) cells, suggesting that the minimum supply of methionine was sufficient to maintain intracellular levels of methionine. Both U937/MTAP(+) and U937/MTAP(-) cells were comparably sensitive to anticancer drugs (cytarabine, methotrexate, clofarabine and 6-thioguanine). The combination of SAM486A and cytarabine was demonstrated to have synergistic cytotoxicity in U937/MTAP(-) cells with regard to cell growth inhibition and apoptosis induction, but not in U937/MTAP(+) cells. Mechanistically, SAM486A altered the intracellular polyamine concentrations and reduced the antiapoptotic proteins. Methionine metabolism and polyamine synthesis can be attractive therapeutic targets in leukemia.

PH-dependent and whole-cell catalytic decolorization of dyes using recombinant dye-decolorizing peroxidase from Rhodococcus jostii.

Dyes in wastewater have adverse effects on the environment and human health. Dye-decolorizing peroxidase (DyP) is a promising biocatalyst to dyes degradation, but the decolorization rates varied greatly which influencing factors and mechanisms remain to be fully disclosed. To explore an effective decolorizing approach, we have studied a DyP from Rhodococcus jostii (RhDyPB) which was overexpressed in Escherichia coli to decolorize four kinds of dyes, Reactive blue 19, Eosin Y, Indigo carmine, and Malachite green. We found the decolorization rates of the dyes by purified RhDyPB were all pH-dependent and the highest one was 94.4% of Malachite green at pH 6.0. ESI-MS analysis of intermediates in the decolorization process of Reactive blue 19 proved the degradation was due to peroxidase catalysis. Molecular docking predicated the interaction of RhDyPB with dyes, and a radical transfer reaction. In addition, we performed decolorization of dyes with whole E. coli cell with and without expressing RhDyPB. It was found that decolorization of dyes by E. coli cell wasdue to both cell absorption and degradation, and RhDyPB expression improved the degradation rates towards Reactive blue 19, Indigo carmine and Malachite green. The effective decolorization of Malachite green and the successful application of whole DyP-overexpressed cells in dye decolorization is conducive to the bioremediation of dye-containing wastewaters by DyPs.

Anaerobic heme recycling by gut microbes: Important methods for monitoring porphyrin production.

Heme is the most abundant species of iron inside the human body and an essential cofactor for numerous electron/chemical group transfer reactions and catalyses, especially those involving O2. Whole anaerobic biomes exist that also depend on heme but lack widespread, O2-dependent pathways for heme synthesis and breakdown. The gastrointestinal tract is an anaerobic ecosystem where many microbes are auxotrophic for heme, and where the abundant members of the Bacteroidetes phylum convert heme into iron and porphyrins. Working with mixtures of these hydrophobic compounds presents challenges for analyses, especially when their source is biological. In this brief chapter, we detail a handful of important methods and point out caveats necessary for their concurrent detection, separation, and quantification.

Enhancing lipid peroxidation via radical chain transfer reaction for MRI guided and effective cancer therapy in mice

Lipid peroxidation (LPO), the process of membrane lipid oxidation, is a potential new form of cell death for cancer treatment. However, the radical chain reaction involved in LPO is comprised of the initiation, propagation (the slowest step), and termination stages, limiting its effectiveness in vivo. To address this limitation, we introduce the radical chain transfer reaction into the LPO process to target the propagation step and overcome the sluggish rate of lipid peroxidation, thereby promoting endogenous lipid peroxidation and enhancing therapeutic outcomes. Firstly, radical chain transfer agent (CTA-1)/Fe nanoparticles (CTA-Fe NPs-1) was synthesized. Notably, CTA-1 convert low activity peroxyl radicals (ROO·) into high activity alkoxyl radicals (RO·), creating the cycle of free radical oxidation and increasing the propagation of lipid peroxidation. Additionally, CTA-1/Fe ions enhance reactive oxygen species (ROS) generation, consume glutathione (GSH), and thereby inactivate GPX-4, promoting the initiation stage and reducing termination of free radical reaction. CTA-Fe NPs-1 induce a higher level of peroxidation of polyunsaturated fatty acids in lipid membranes, leading to highly effective treatment in cancer cells. In addition, CTA-Fe NPs-1 could be enriched in tumors inducing potent tumor inhibition and exhibit activatable T1-MRI contrast of magnetic resonance imaging (MRI). In summary, CTA-Fe NPs-1 can enhance intracellular lipid peroxidation by accelerating initiation, propagation, and inhibiting termination step, promoting the cycle of free radical reaction, resulting in effective anticancer outcomes in tumor-bearing mice.

A Formal γ-C-H Functionalization of Carboxylic Acids Guided by Metal-Nitrenoids as an Unprecedented Mechanistic Motif.

Harnessing the key intermediates in metal-catalyzed reactions is one of the most essential strategies in the development of selective organic transformations. The nitrogen group transfer reactivity of metal-nitrenoids to ubiquitous C-H bonds allows for diverse C-N bond formation to furnish synthetically valuable aminated products. In this study, we present an unprecedented reactivity of iridium and ruthenium nitrenoids to generate remote carbocation intermediates, which subsequently undergo nucleophile incorporation, thus developing a formal γ-C-H functionalization of carboxylic acids. Mechanistic investigations elucidated a unique singlet metal-nitrenoid reactivity to initiate an abstraction of γ-hydride to form the carbocation intermediate that eventually reacts with a broad range of carbon, nitrogen, and oxygen nucleophiles, as well as biorelevant molecules. Alternatively, the same intermediate can lead to deprotonation to afford β,γ-unsaturated amides in a less nucleophilic solvent.

Facile Access to Cationic Methylstannylenes and Silylenes Stabilized by E-Pt Bonding and their Methyl Group Transfer Reactivity.

We describe a family of cationic methylstannylene and chloro- and azidosilylene organoplatinum(II) complexes supported by a neutral, binucleating ligand. Methylstannylenes MeSn:+ are stabilized by coordination to PtII and are formed by facile Me group transfer from dimethyl or monomethyl PtII complexes, in the latter case triggered by concomitant B-H, Si-H, and H2 bond activation that involves hydride transfer from Sn to Pt. A cationic chlorosilylene complex was obtained by formal HCl elimination and Cl- removal from HSiCl3 under ambient conditions. The computational studies show that stabilization of cationic methylstannylenes and cationic silylenes is achieved through weak coordination to a neutral N-donor ligand binding pocket. The analysis of the electronic potentials, as well as the Laplacian of electron density, also reveals the differences in the character of Pt-Si vs. Pt-Sn bonding. We demonstrate the importance of a ligand-supported binuclear Pt/tetrel core and weak coordination to facilitate access to tetrylium-ylidene Pt complexes, and a transmetalation approach to the synthesis of MeSnII :+ derivatives.

Ketone-Derived Pro-aromatic Reagents for Radical Group Transfer Reactions and Deconstructive Functionalizations

AbstractThe recent prominence of ketones as handles for sp3-rich radicals has expanded the paradigm of synthetic utility of ketones, putting the ubiquitous functional group once again into the spotlight in recent years. One emerging strategy arose through ketone-derived pro-aromatic reagents in the form of dihydrobenzothiazoline (BTZ), dihydroquinazolinone (DHQZ), dihydropyrazole (DHP), and dihydro-1,2,4-triazole (DHT) as key intermediates for aromaticity-promoted C–C bond homolytic fission. The formed sp3-radicals could then participate in various radical functionalizations, including alkylations, arylations, olefination, alkynylation, silylations, amination, thiolation, and deuteration, among others, either in photocatalytic, thermal, or oxidative conditions. In this review, we highlight the implications and recent advances in using these pro-aromatic reagents in radical group transfer reactions and deconstructive functionalization.1 Introduction2 Aromatization-Driven C–C Bond Scission of Ketones3 Photochemical Reactions of Ketone-Derived Pro-aromatic Reagents4 Non-photochemical Reactions of Ketone-Derived Pro-aromatic Reagents5 Conclusion and Future Outlook

Preparation of CuO loaded cation exchange resin composites and its degradation of polyacrylamide aqueous solution

Macroporous cation exchange resins (CER) were used as carriers, and CuO loaded cation exchange resin composites was successfully prepared under thermostatic oscillation and hydrothermal conditions. The results showed that the as-prepared composites exhibited obvious shell-core structure. The different amounts of NaOH affected the micro morphology of CuO on the surface and in the internal pores of the resin, and also affected the percentage content of Cu element. XRD characterization clearly revealed that the products were monoclinic crystal system CuO species with a grain size of about 16 nm. The highest degradation rate of polyacrylamide (PAM) by CuO@IER-1g reached 81.94%, after 6 cycles CuO@CER-1g has still good photocatalytic activity, and the decrease in degradation rate was the combined effect from the adsorption of ion exchange resins and the electron-hole pairs formed by CuO and a series of free radical transfer reactions under ultraviolet light. This study has important theoretical basis and practical significance for enriching ion exchange theory, developing the photocatalytic industry, and purifying the environment.

Azoxy Compounds—From Synthesis to Reagents for Azoxy Group Transfer Reactions

AbstractThe azoxy functional group is an important structural motif and represents the formally oxidized counterpart of the azo group. Azoxy compounds find numerous applications ranging from pharmaceuticals to functional materials, yet their synthesis remains underdeveloped with a main focus on the formation symmetric azoxy compounds. To overcome challenges in the synthesis of such unsymmetric azoxy compounds, we designed a process employing readily accessible nitroso compounds and iminoiodinanes. This method builds on the use of visible light irradiation to generate a triplet nitrene from iminoiodinanes, which is trapped by nitroso arenes to give access to sulfonyl‐protected azoxy compounds with a good substrate scope and functional group tolerance. We further describe two applications of these sulfonyl‐protected azoxy compounds as radical precursors in synthesis, where the whole azoxy group can be transferred and employed in C(sp3)−H functionalization of ethers or 1,2‐difunctionalization of vinyl ethers. All of the reactions occurred at room temperature under visible light irradiation without the addition of any photoredox catalysts and additives. Control experiments, mechanism investigations, and DFT studies well explained the observed reactivity.

Azoxy Compounds-From Synthesis to Reagents for Azoxy Group Transfer Reactions.

The azoxy functional group is an important structural motif and represents the formally oxidized counterpart of the azo group. Azoxy compounds find numerous applications ranging from pharmaceuticals to functional materials, yet their synthesis remains underdeveloped with a main focus on the formation symmetric azoxy compounds. To overcome challenges in the synthesis of such unsymmetric azoxy compounds, we designed a process employing readily accessible nitroso compounds and iminoiodinanes. This method builds on the use of visible light irradiation to generate a triplet nitrene from iminoiodinanes, which is trapped by nitroso arenes to give access to sulfonyl-protected azoxy compounds with a good substrate scope and functional group tolerance. We further describe two applications of these sulfonyl-protected azoxy compounds as radical precursors in synthesis, where the whole azoxy group can be transferred and employed in C(sp3 )-H functionalization of ethers or 1,2-difunctionalization of vinyl ethers. All of the reactions occurred at room temperature under visible light irradiation without the addition of any photoredox catalysts and additives. Control experiments, mechanism investigations, and DFT studies well explained the observed reactivity.

Multielectron Bond Cleavage Processes Enabled by Redox-Responsive Phosphinimide Ligands.

The activation of small molecules via multielectron redox processes offers promise in mediating difficult transformations related to energy conversion processes. While molecular systems that engage in one- and two-electron redox processes are widespread, those that participate in the direct transfer of four or more electrons to small molecules are very rare. To that end, we report a mononuclear CrII complex competent for the 4-electron reduction of dioxygen (O2) and nitrosoarenes. These systems additionally engage in facile two-electron group transfer reactivity, including O atom excision and nitrene transfer. Structural, spectroscopic, and computational studies support bond activation processes that intimately occur at a mononuclear chromium(phosphinimide) center and highlight the unusual structural responsiveness of the phosphinimides in stabilizing a range of metal redox states.

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.