Application of the novel 5-chloro-2,2,3,3,4,4,5,5-octafluoro-1-pentyl chloroformate derivatizing agent for the direct determination of highly polar water disinfection byproducts

A novel derivatizing agent, 5-chloro-2,2,3,3,4,4,5,5-octafluoropentyl chloroformate (ClOFPCF), was synthesized and tested as a reagent for direct water derivatization of highly polar and hydrophilic analytes. Its analytical performance satisfactorily compared to a perfluorinated chloroformate previously described, namely 2,2,3,3,4,4,5,5-octafluoropentyl chloroformate (OFPCF). The chemical properties (reactivity, selectivity, derivatization products, and their chromatographic and spectral features) for ClOFPCF were investigated using a set of 39 highly polar standard analytes, including, among others, hydroxylamine, malic and succinic acids, resorcinol, hydroxybenzaldehyde, and dihydroxybenzoic acid. Upon derivatization, the analytes were extracted from the aqueous solvent and analyzed by gas chromatography (GC)-mass spectrometry (MS) in the electron-capture negative ionization (ECNI) mode. Positive chemical ionization (PCI)-MS was used for confirming the molecular ions, which were virtually absent in the ECNI mass spectra. ClOFPCF showed good reaction efficiency, good chromatographic and spectroscopic properties (better than with OFPCF), good linearity in calibration curves, and low detection limits (0.3–1 μg/L). A unique feature of the derivatizations with ClOFPCF, and, in general, highly fluorinated chloroformates, is their effectiveness in reacting with carboxylic, hydroxylic, and aminic groups at once, forming multiply-substituted non-polar derivatives that can be easily extracted from the aqueous phase and determined by GC-ECNI-MS. The entire procedure from raw aqueous sample to ready-to-inject hexane solution of the derivatives requires less than 10 min. Another benefit of this procedure is that it produced stable derivatives, with optimal volatility for GC separation, and high electron affinity, which allows their detection as negative ions at trace level. In addition, their mass spectra exhibits chlorine isotopic patterns that clearly indicate how many polar hydrogens of the analyte undergo derivatization. Finally, derivatization with ClOFPCF was used successfully to identify 13 unknown highly polar disinfection byproducts (DBPs) in ozonated fulvic and humic acid aqueous solutions and in real ozonated drinking water.     

Determination of volatile organic acids in tobacco by single‐drop microextraction with in‐syringe derivatization followed by GC‐MS

In this work, the novel technique based on headspace single‐drop microextraction with in‐syringe derivatization followed by GC‐MS was established to determine the volatile organic acids in tobacco. The parameters for headspace single‐drop microextraction and in‐syringe derivatization were optimized, including extraction time, and volume of derivatization reagent and in‐syringe derivatization time. The method validations including linearity, precision, recovery and LOD were also studied. The obtained results illustrated that the optimized technique was easy, highly efficient and sensitive. Finally, the proposed method was successfully applied to the analyses of volatile organic acids in tobacco samples with seven different brands. It was further demonstrated that the present technique developed in this study does offer a simple and fast approach to determine volatile organic acids in tobacco.     

Comparison of highly-fluorinated chloroformates as direct aqueous sample derivatizing agents for hydrophilic analytes and drinking-water disinfection by-products

Four highly-fluorinated alkyl and aryl chloroformates, including 2,2,3,3,4,4,5,5-octafluoro-1-pentyl chloroformate (OFPCF), 2,3,4,5,6-pentafluorobenzyl chloroformate (PFBCF), 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octyl chloroformate (TDFOCF), and 2-(2,3,4,5,6-pentafluorophenoxy)-ethyl chloroformate (PFPECF), were synthesized and tested as reagents for the direct water derivatization of polar and hydrophilic analytes. The goal of this research was to develop an optimal derivatizing agent to aid in the identification of highly polar ozonation drinking water disinfection by-products (DBPs) that are believed to be missed with current analytical procedures. The chemical properties (reactivity, selectivity, derivatization products, and their chromatographic and spectral features) for the four chloroformates were investigated using a set of highly polar standard analytes, including malic and tartaric acids, hydroxylamine, valine, 2-aminoethanol, resorcinol, 1,3,5-trihydroxybenzene, and 2,4-dihydroxybenzoic acid. Upon derivatization, the analytes were extracted from the aqueous solvent and analyzed by gas chromatography (GC)-mass spectrometry (MS) in the electron capture negative ionization (ECNI) mode. Positive chemical ionization (PCI)-MS was used for confirmation of molecular ions that were weak or absent in ECNI mass spectra. Of the four derivatizing reagents tested, OFPCF showed the best performance, with good reaction efficiency, good chromatographic and spectroscopic properties, low detection limits (10-100 fmol), and a linear response more than two orders of magnitude. Further, the entire procedure from raw aqueous sample to ready-to-inject hexane solutions of the derivatives requires less than 10 min. PFBCF showed ideal applicability for derivatizing aminoalcohols and aminoacids. The two chloroformates with the highest intrinsic stability (TDFOCF and PFPECF) failed to derivatize some of the analytes. Finally, the OFPCF derivatizing agent was tested with simulated ozonated drinking water (aqueous fulvic acid treated with ozone), and three highly polar reaction by-products were determined.     

Speciation of inorganic and tetramethyltin by headspace solid‐phase microextraction and gas chromatography–mass spectrometry

A headspace solid‐phase microextraction (HS‐SPME) method coupled to GC‐MS was developed in order to determine trace levels of tetramethyltin (TeMT) and inorganic tin (iSn) after ethylation to tetraethyltin (TeET) in various matrices. The derivatization of iSn and the extraction of both TeMT and iSn as TeET were performed in one step. Sodium tetraethylborate (NaBEt₄) was used as derivatization agent and the volatile derivatives were absorbed on a PDMS‐coated fused silica fiber. The conditions for the HS‐SPME procedure were optimized in order to gain in repeatability and sensitivity. Several critical parameters of GC‐MS were also studied. The detection of TeMT and iSn as TeET peaks was performed by the SIM mode. The precision of the proposed method is satisfactory providing RSD values below 10% for both tin species and good linearity up to 10 μg/L. The developed method was successfully applied to the determination of tin species in several samples like canned fish, fish tissues, aquatic plants, canned mineral water and sea water. The proposed HS‐SPME‐GC‐MS method was proved suitable to monitor the concentration levels of toxic tin compounds in environmental and biological samples.     

Pressure‐Tunable Dual‐Column Ensembles for High‐Speed GC and GC/MS

A series‐coupled ensemble of two capillary GC columns of different selectivity with an adjustable pressure at the column junction point is used to obtain tunable selectivity for high‐speed GC and GC/TOFMS. An electronic pressure controller with a 0.1‐psi step size is used to obtain numerous computer‐selected unique selectivities. System configurations for conventional, atmospheric‐pressure outlet operation with flame ionization detection and for vacuum‐outlet operation with photoionization detection are described for GC‐only experiments. Polydimethylsiloxane is used as the non‐polar column and polyethylene glycol (atmospheric outlet) or triflouropropylpolysiloxane (vacuum outlet) is used as the polar column. For GC/TOFMS experiments, 5% phenyl polydimethylsiloxane was used as the non‐polar column, and polyethylene glycol was used as the polar column. The time‐of‐flight mass spectrometer can acquire up to 500 complete mass spectra per second. Since spectral continuity is achieved across the entire chromatographic peak profile, severely overlapping peaks can be spectrally deconvoluted for high‐speed characterization of completely unknown mixtures. For mixture components with significantly different fragmentation patterns, spectral deconvolution can be achieved for chromatographic peak separations of as little as 6.0 ms. This can result is very large peak capacity for time compressed (not completely resolved) chromatograms. The use of columns with tunable selectivity allows for precise peak‐position control, which can result in more efficient utilization of available peak capacity and thus further time compression of chromatograms. The limits of tunability and deconvolution are tested for near co‐elutions of different classes of hydrocarbon compounds as well as for more multi‐functional mixtures.     

Ultrasound‐assisted emulsification microextraction combined with injection‐port derivatization for the determination of some chlorophenoxyacetic acids in water samples

An efficient method based on ultrasound‐assisted emulsification microextraction followed by injection‐port derivatization GC analysis was developed to determine 2,4‐dichlorophenoxyacetic acid (2,4‐D) and 4‐chloro‐2‐methylphenoxyacetic acid (MCPA) in natural water samples. In this procedure, 12.5 μL of 1‐undecanol was injected slowly into a 12 mL home‐designed centrifuge glass vial containing an aqueous sample of the analytes located inside an ultrasonic water bath. The resulting emulsion was centrifuged, and 1 μL of the separated organic solvent together with 1 μL of the derivatization reagent were injected into a GC equipped with a flame ionization detector. Several factors that influence the derivatization and extraction were optimized. Under the optimal conditions, the LODs were 0.33 and 1.7 μg/L for MCPA and 2,4‐D, respectively. Preconcentration factors of 670 and 836 were obtained for MCPA and 2,4‐D, respectively. The precision of the proposed method was evaluated in terms of repeatability, which was <5.7% (n = 5). The applicability of the proposed method was evaluated by extraction and determination of chlorophenoxyacetic acids from some natural waters, which indicated that the matrices of natural waters have no significant effect on the extraction and derivatization efficiency of this method.     

Development of single‐drop microextraction and simultaneous derivatization followed by GC‐MS for the determination of aliphatic amines in tobacco

In this work, for the first time, headspace (HS) single‐drop microextraction and simultaneous derivatization followed by GC‐MS was developed to determine the aliphatic amines in tobacco samples. In the HS extraction procedure, the mixture of derivatization reagent and organic solvent was employed as the extraction solvent for HS single‐drop microextraction and in situ derivatization of aliphatic amine in the samples. Fast extraction and simultaneous derivatization of the analytes were performed in a single step, and the obtained derivatives in the microdrop extraction solvent were analyzed by GC‐MS. The optimized experiment conditions were: sample preparation temperature of 80°C and time of 30 min, HS extraction solvent (the mixture of benzyl alcohol and 2,3,4,5,6‐pentafluorobenzaldehyde) volume of 2.0 μL, extraction time of 90 s. With the optimal conditions, the method validations were also studied. The method has good linearity (R² more than 0.99), accepted precision (RSD less than 13%), good recovery (98–104%) and low limit of detection (0.11–0.97 μg/g). Finally, the proposed technique was successfully applied to the analyses of aliphatic amines in tobacco samples of seven different brands. It was further demonstrated that the proposed method offered a simple, low‐cost and reliable approach to determine aliphatic amines in tobacco samples.     

Determination of Acrylamide and Acrolein in Smoke from Tobacco and E-Cigarettes

Acrylamide and acrolein are two short-chained hazardous compounds with neurotoxic, carcinogenic, and mutagenic effects. The aim of this paper is to describe a fast and simple procedure for simultaneous determination of both acrylamide and acrolein under standard conditions, suggest a suitable calibration protocol for custom analysis, and demonstrate its applicability to the analysis of gaseous products from, e.g., cigarettes, cigars, or electronic cigarettes. A gas chromatography–mass spectrometry (GC–MS) method was developed to quantify acrylamide and acrolein in smoke vapor from electronic cigarettes, tobacco cigarettes, and cigars. Nonionic and highly polar molecules with a low boiling point and molecular mass need a suitable derivatization method to achieve appropriate retention and selectivity on commonly used relatively nonpolar stationary phases and to enhance the molecular mass for easy MS detection. The derivatization of acrylamide and acrolein was carried out by a bromination method with elemental bromine. The dibromo derivatives were extracted into an organic solvent and following a dehydrobromination procedure the samples were injected into the GC–MS system. Important experimental parameters were varied, after which the bromination time was defined as 30 min, and the injector temperature and the starting temperature of gradient were set at 280 and 50 °C respectively. Acrolein was found in all tested samples, while acrylamide was detected only in smoke from normal tobacco. Possible mechanisms for the formation of these unsaturated compounds in the samples are discussed. After its validation the newly developed method was successfully and reliably applied to the analysis of both compounds. This short method provides an easy way to determine acrylamide and acrolein in gaseous samples.

     

Simultaneous determination of fenpropimorph and the corresponding metabolite fenpropimorphic acid in soil

Summary An analytical procedure for the simultaneous determination of fenpropimorph and its main metabolite fenpropimorphic acid in soil is reported. Extraction with acetone/water (2:1), liquid/liquid partition with dichloromethane and clean-up using gel permeation chromatography is employed to concentrate the analytes. Methylation of the polar metabolite is absolutely required for GC/MS and GC/NPD. The parent compound fenpropimorph is not influenced by this derivatization step. The detection limits are 0.005 mg/kg for fenpropimorph and 0.010 mg/kg for fenpropimorphic acid.     

大气颗粒物滤膜中极性有机物在线衍生装置的设计与应用

设计制作了一套用于气相色谱-质谱(GC-MS)分析极性有机物的在线衍生装置,并将其应用于大气颗粒物样品中极性有机物的检测.将大气颗粒物滤膜样品置于GC-MS进样口,通过使用套针组件,匀速引入气态衍生试剂N-甲基-Ⅳ-(三甲基硅烷)三氟乙酰胺(MSTFA),使其在衬管内于310℃下与待测物接触,10 min即可完成硅烷化...     

Fully automated reagent peak‐free liquid chromatography fluorescence analysis of highly polar carboxylic acids using a column‐switching system and fluorous scavenging derivatization

In this study, we combined a column‐switching system with a fluorous scavenging derivatization method to develop a fully automated reagent peak‐free LC fluorescence detection protocol for the analysis of highly polar carboxylic acids. In this method, highly polar carboxylic acids were derivatized with fluorescent 1‐pyrenemethylamine in the presence of 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide and 1‐hydroxy‐1H‐benzotriazole. Residual excess of the unreacted reagent was tagged with 2‐(perfluorooctyl)ethyl isocyanate and then removed selectively using a fluorous column‐switching system placed in front of an analytical reversed‐phase column. The signal of the fluorous‐tagged unreacted reagent was completely absent in the resulting chromatograms; therefore, it did not interfere with the quantification of each acid especially those eluted before 20 min. The detection limits (S/N = 3) for the examined acids were in the range from 4.0 to 22 fmol per injection. We have applied this method to comparative analysis of highly polar carboxylic acids in urine samples obtained from diabetes mellitus type‐II model mice and their control.     

Simultaneous determination of β2‐agonists in human urine by fast‐gas chromatography/mass spectrometry: method validation and clinical application

A fast screening protocol was developed and validated for the simultaneous determination of 15 β₂‐agonists in human urine (bambuterol, cimbuterol, clenbuterol, fenoterol, formoterol, isoproterenol, mapenterol, metaproterenol, procaterol, ractopamine, ritodrine, salbutamol, salmeterol, terbutaline, tulobuterol). The overall sample processing includes deconjugation with enzyme hydrolysis, liquid–liquid extraction, followed by derivatization of the extract and detection of β₂‐agonists trimethylsilyl‐derivatives by fast‐gas chromatography/electron impact–mass spectrometry (fast‐GC/EI‐MS). Sample extraction and derivatization were optimized with the purpose of improving recoveries and reaction yields for a variety of analytes with different structures simultaneously, while keeping the procedure simple and reliable. Validation parameters were determined for each analyte under investigation, including selectivity, linearity, intra‐ and inter‐assay precision, extraction recoveries and signal to noise ratio (S/N) at the lowest calibration level. Fast‐GC/MS sequences, based on the use of short columns, high carrier‐gas velocity and fast temperature ramping, allow considerable reduction of the analysis time (7 min), while maintaining adequate chromatographic resolution. The overall GC cycle time was less than 9 min, allowing a processing rate of 6 samples/h. High MS‐sampling rate, using a benchtop quadrupole mass analyzer, resulted in accurate peak shape definition under both scan and selected ion monitoring modes, and high sensitivity in the latter mode. The method was successfully tested on real samples arising from clinical treatments. Copyright © 2009 John Wiley & Sons, Ltd.     

Derivatization of chiral carboxylic acids with (S)‐anabasine for increasing detectability and enantiomeric separation in LC/ESI‐MS/MS

A simple and practical derivatization procedure for increasing the detectability and enantiomeric separation of chiral carboxylic acids in LC/ESI‐MS/MS has been developed. (S)‐Anabasine (ANA) was used as the derivatization reagent and rapidly reacted with carboxylic acids [3‐hydroxypalmitic acid (3‐OH‐PA), 2‐(β‐carboxyethyl)‐6‐hydroxy‐2,7,8‐trimethylchroman (γ‐CEHC), and etodolac] in the presence of 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholium chloride. The resulting ANA‐derivatives were highly responsive in ESI‐MS operating in the positive‐ion mode and gave characteristic product ions during MS/MS, which enabled sensitive detection using selected reaction monitoring; the detection responses of the ANA‐derivatives were increased by 20–160‐fold over those of the intact carboxylic acids and the limits of detection were in the low femtomole range (1.8–11 fmol on the column). The ANA‐derivatization was also effective for the enatiomeric separation of the chiral carboxylic acids; the resolution was 1.92, 1.75, and 2.03 for 3‐OH‐PA, γ‐CHEC, and etodolac, respectively. The derivatization procedure was successfully applied to a biological sample analysis; the derivatization followed by LC/ESI‐MS/MS enabled the separation and detection of trace amounts of 3‐OH‐PA in neonatal dried blood spot and γ‐CEHC in human saliva with a simple pretreatment and small sample volume.     

GC separation of amino acid enantiomers via derivatization with heptafluorobutyl chloroformate and Chirasil‐L‐Val column

Heptafluorobutyl chloroformate (HFBCF), a recently introduced derivatization reagent, was examined in enantioseparation of amino acids (AAs) by GC. Twenty proteinogenic AAs, plus ornithine, cystine and 4‐fluorophenylalanine (internal standard) were treated with the reagent and separation properties of the derivatives were assessed on a Chirasil‐Val capillary column. Nineteen AA enantiomers were efficiently separated in 43 min except proline, arginine and cystine. The HFBCF derivatives of the studied DL ‐AAs show improved separation over other chloroformate‐based derivatives hitherto reported. A combination of the improved and faster separation with a simple derivatization protocol, involving an immediate one‐step reaction–extraction in two‐phase aqueous‐organic medium, and low elution temperatures extend application of HFBCF to chiral AA analysis.     

Metabolite analysis in Curcuma domestica using various GC‐MS and LC‐MS separation and detection techniques

The metabolic profile of polar (methanol) and non‐polar (hexane) extracts of Curcuma domestica, a widely used medicinal plant, was established using various different analytical techniques, including GC‐FID, GC‐MS, HR‐GC‐MS and analytical HPLC‐ESI‐MS/MS by means of LTQ‐Orbitrap technology. The major non‐volatile curcuminoids curcumin, demethoxycurcumin and bisdemethoxycurcumin were identified when their chromatographic and precursor ion masses were compared with those of authentic standard compounds. In this paper we describe for the first time a GC/MS‐based method for metabolic profiling of the hydrophilic extract. We also identified 61 polar metabolites as TMS derivatives. Copyright © 2009 John Wiley & Sons, Ltd.     

Stereochemical analysis of 3,4-methylenedioxymethamphetamine and its main metabolites by gas chromatography/mass spectrometry

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is consumed as the racemate but some metabolic steps are enantioselective. In addition, chiral properties are preserved during MDMA biotransformation. A quantitative analytical methodology using gas chromatography/mass spectrometry (GC/MS) to determine enantioselective disposition in the body of MDMA and its main metabolites including 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-methoxyamphetamine (HMA) was developed. Plasma and urine samples were collected from a male volunteer. The analysis of MDMA, MDA, and 4-hydroxy-3-methoxy metabolites by GC/MS required a two-step derivatization procedure. The first step consisted of derivatization of the amine with enantiomerically pure Mosher's reagent ((R)-MTPCl). Triethylamine was used as a base to neutralize hydrochloric acid formed during the reaction allowing quantitative derivatization, which resulted in a substantial improvement in the sensitivity of the method compared with other previously described techniques. Further treatment with ammonium hydroxide was required since both amine and hydroxyl groups underwent derivatization in the reaction. Ammonium hydroxide breaks bonds formed with hydroxyl groups without affecting amine derivatives. The second derivatization step using hexamethyldisilazane was needed for metabolites containing phenol residues. This derivatization method permitted the stereochemically specific study of MDMA and its main monohydroxylated metabolites by GC/MS. A detailed study of the chemical reactions involved in the derivatization steps was indispensable to develop a straightforward, sensitive, and reproducible method for the analysis of the parent drug compound and its metabolites.     

Rapid determination of bisphenol A in drinking water using dispersive liquid‐phase microextraction with in situ derivatization prior to GC‐MS

This paper described a novel approach for the determination of bisphenol A by dispersive liquid‐phase microextraction with in situ acetylation prior to GC‐MS. In this derivatization/extraction method, 500 μL acetone (disperser solvent) containing 30.0 μL chlorobenzene (extraction solvent) and 30.0 μL acetic anhydride (derivatization reagent) was rapidly injected into 5.00 mL aqueous sample containing bisphenol A and K₂CO₃ (0.5% w/v). Within a few seconds the analyte was derivatized and extracted at the same time. After centrifugation, 1.0 μL of sedimented phase containing enriched analyte was determined by GC‐MS. Some important parameters, such as type and volume of extraction and disperser solvent, volume of acetic anhydride, derivatization and extraction time, amount of K₂CO₃, and salt addition were studied and optimized. Under the optimum conditions, the LOD and the LOQ were 0.01, 0.1 μg/L, respectively. The experimental results indicated that there was linearity over the range 0.1–50 μg/L with coefficient of correlation 0.9997, and good reproducibility with RSD 3.8% (n = 5). The proposed method has been applied for the analysis of drinking water samples, and satisfactory results were achieved.     

Structural elucidation of amino amide‐type local anesthetic drugs and their main metabolites in urine by LC‐MS after derivatization and its application for differentiation between positional isomers of prilocaine

The demand for clinical toxicology analytical methods for identifying drugs of abuse and medicinal drugs is steadily increasing. Structural elucidation of amino amide‐type local anesthetic drugs and their main metabolites by GC‐EI‐MS and LC‐ESI‐MS/MS is of great analytical challenge. These compounds exhibit only/mostly fragments/product ions representing the amine‐containing residue, while the aromatic amide moiety remains unidentified. This task becomes even more complicated when discrimination between positional isomers of such compounds is required. Here, we report the development of a derivatization procedure for the differentiation and structural elucidation of a mixture of local anesthetic drugs and their metabolites that possess tertiary and secondary amines in water and urine. A method based on two sequential “in‐vial” instantaneous derivatization processes at ambient temperature followed by LC‐ESI‐MS/MS analysis was developed. 2,2,2‐Trichloro‐1,1‐dimethylethyl chloroformate (TCDMECF) was utilized to selectively convert the secondary amines into their carbamate derivatives, followed by hydrogen peroxide addition to produce the corresponding tertiary amine oxides. The resulting derivatives exhibited rich fragmentation patterns, enabling improved structural elucidation of the original compounds. The developed method was successfully applied to the differentiation and structural elucidation of prilocaine and its four positional isomers, which all possess similar GC and LC retention times and four of them exhibit almost identical EI‐MS and ESI‐MS/MS spectra, enabling their structural elucidation in a single LC‐ESI‐MS/MS analysis. The developed technique is fast and simple and enables discrimination between isomers based on different diagnostic ions/fragmentation patterns.     

Single‐drop microextraction followed by in‐syringe derivatization and GC‐MS detection for the determination of parabens in water and cosmetic products

A single‐drop microextraction (SDME) method followed by in‐syringe derivatization and GC‐MS determination has been developed for analysis of five parabens, including methyl, ethyl, isopropyl, n‐propyl and n‐butyl paraben in water samples and cosmetic products. N,O‐Bis(trimethylsilyl)acetamide (BSA) was used as derivatization reagent. Derivatization reaction was performed inside the syringe barrel using 0.4 μL of BSA. Parameters that affect the derivatization yield such as temperature and time of the reaction were studied. In addition, experimental SDME parameters such as selection of organic solvent, addition of salt, extraction time and extraction temperature were investigated and optimized. The RSD of the method for aqueous samples varied from 8.1 to 13%. The LODs ranged from 0.001 (n‐butyl paraben) to 0.015 (methyl paraben) μg/L, and the enrichment factors were between 23 and 150.     

A Second‐Coordination‐Sphere Strategy to Modulate Nickel‐ and Palladium‐Catalyzed Olefin Polymerization and Copolymerization

Transition‐metal‐catalyzed copolymerization reactions of olefins with polar‐functionalized comonomers are highly important and also highly challenging. A second‐coordination‐sphere strategy was developed to address some of the difficulties encountered in these copolymerization reactions. A series of α‐diimine ligands bearing nitrogen‐containing second coordination spheres were prepared and characterized. The properties of the corresponding nickel and palladium catalysts in ethylene polymerizations and copolymerizations were investigated. In the nickel system, significant reduction in polymer branching density was observed, while lower polymer branching densities, as well as a wider range of polar monomer substrates, were achieved in the palladium system. Control experiments and computational results reveal the critical role of the metal−nitrogen interaction in these polymerization and copolymerization reactions.