E2 Mechanism Research Articles

Dehydrochlorination of 1, 1, 2-trichloroethane over SiO2-supported alkali and transition metal catalysts: Tunable selectivity controlled by the acid - base properties of the catalysts

Dehydrochlorination of 1, 1, 2-trichloroethane was performed on SiO2 supported alkali metal (Na. K, Cs) and transition metal (Mn, Ni, Zn) catalysts. The surface basicity or acidity of the catalyst exerted great influence on catalytic behaviors. The catalysts with higher amount of base or acid sites resulted in higher activity due to more adsorption sites for reactant. The basic catalysts (Cs/SiO2 and K/SiO2) tended to form vinylidene chloride with a selectivity up to 80 %; the neutral catalysts (Na/SiO2 and SiO2) tended to form 1, 2-dichloroethene with a selectivity up to about 80 %; the acidic catalysts (Zn/SiO2, Mn/SiO2 and Ni/SiO2) tended to form 1, 2-dichloroethene with a selectivity up to 96 %. Proposed reaction mechanisms included an E1cb mechanism with a carbanion intermediate on the basic catalysts, an E2 concerted mechanism on the neutral catalysts, and an E1 mechanism with a carbonium intermediate on the acidic catalysts.

Elimination Reactions of Aryl Furylacetates Promoted by R2NH in MeCN: Effects of Base Solvent and β‐Aryl Group on the Ketene‐forming Transition State

Ketene‐forming elimination from C4H3(O)CH2C(O)OC6H3‐2‐X‐4‐NO2 (1) promoted by R2NH in MeCN has been studied. The reactions produced elimination products and exhibited second‐order kinetics with Brönsted β = 0.51, and |βlg| = 0.47–0.53, indicating that the reaction proceeds by the E2 mechanism via an E2‐central transition state. Comparison of β, |βlg|, ΔH≠, and ΔS≠ values for R2NH‐promoted eliminations from ArCH2C(O)OC6H3‐2‐X‐4‐NO2 reveals that the transition‐state structures for Ar = furyl and thienyl are similar and more symmetrical than that for Ar = Ph. This outcome has been attributed to the greater double bond stabilizing ability of the former than that of the latter.

Ethanol dehydration on γ-Al2O3: Effects of partial pressure and temperature

Ethanol dehydration was investigated using platelet γ-Al2O3 over a wide range of reaction temperature (180–300°C) and ethanol partial pressure (0.5–2kPa) by X-ray diffraction, ethanol Temperature-programmed desorption and reactions. The turnover frequencies for commercial and platelet γ-Al2O3 were almost identical (1.2–1.3×10−2 ethanol/sites) when normalized to the number of ethoxide quantified by ethanol TPD. The desorption barrier of ethoxide was 183.6kJ/mol, similar to the activation barrier of ethylene formation. These results demonstrate that ethoxide is a key intermediate rather than molecular ethanol, possibly suggesting an E1 mechanism for ethylene formation, consistent with recent spectroscopic studies. Detailed kinetic measurements demonstrate the nature of the species on alumina surface varied with reaction temperature. At low temperature (180°C), the ethanol dimer, one of which would be the ethoxide, saturated the surface, leading to the inhibition of ethylene formation and constant ether formation rates with ethanol pressure. At high temperature (260°C), the ethanol monomer became dominant, consistent with the constant ethylene formation rates and increased ether formation rates with ethanol pressure. The apparent activation energies also changed with reaction temperature and ethanol partial pressure. Especially, the inhibition by ethanol dimer clearly contributed the increased apparent activation barrier at 180°C.

Insight into the gas‐phase glycerol dehydration on transition metal modified aluminium phosphates and zeolites

AbstractBACKGROUNDThe production of biodiesel has notably increased in recent years, with glycerol as the main by‐product, an important raw material in the production of value‐added products. Those obtained by dehydration are especially important.RESULTSGas phase dehydration of glycerol has been tested on mesoporous AlPO4 and modified AlPO4, with a small amount (1 wt%) of a transition metal (Co, Cu, Cr, Fe), calcined at 450°C and 650°C, and compared with some commercial zeolites (HZSM and HY). All the catalysts were active in the reaction, the phosphates showing better catalytic behaviour than the zeolites. The main products of the reaction were acrolein and hydroxyacetone.CONCLUSIONSThe positive effect of metal on the catalytic behaviour of AlPO4 in the dehydration has been verified, attaining the maximum yield to acrolein (54%) on AlCoPO650 with 50 mg of catalyst and 280°C of reaction temperature. Furthermore, the phosphates did not suffer deactivation after 22 h reaction, whereas the zeolites suffered a strong loss of activity (around 70%) due to blockage of the micropores by coke. Moreover, the yield to acrolein decreased with time, while the yield to hydroxyacetone increased. An E2 mechanism for the acrolein formation and E1 for the hydroxyacetone formation have been proposed. © 2017 Society of Chemical Industry

Enantioselective Synthesis of anti-syn-Trihalides and anti-syn-anti-Tetrahalides via Asymmetric β-Elimination.

Structural motifs containing contiguous halide-bearing stereocenters are common in natural products as well as bioactive molecules. A few successful examples have been reported in the area of asymmetric vicinal dihalogenation of alkenes for accessing dihalogenated products; in this report, an alternative generation method of contiguous halide-bearing stereocenters α,β,γ,δ relative to carbonyl group in excellent enantioselectivity is proposed by utilizing a Song's oligoEG catalyst-catalyzed asymmetric β-elimination. According to this methodology, a wide range of anti-syn-trihalides and anti-syn-anti-tetrahalides with high levels of enantioselectivity were synthesized. The synthetic utility of the contiguous halide-bearing stereocenters was demonstrated by several transformations. The results of high-resolution mass spectrometry indicated that the favorable interaction between catalyst and one of the enantiomers of racemic contiguously multihalogenated ketone contributed to the original enantioselectivity of dehydrohalogenation. A deuterium kinetic isotope effect experiment revealed that this β-elimination reaction proceeds by the E2 mechanism. This strategy opens a new pathway for the asymmetric synthesis of contiguous halide-bearing stereocenters of great complexity.

Enhancing the catalytic activity of hydronium ions through constrained environments

The dehydration of alcohols is involved in many organic conversions but has to overcome high free-energy barriers in water. Here we demonstrate that hydronium ions confined in the nanopores of zeolite HBEA catalyse aqueous phase dehydration of cyclohexanol at a rate significantly higher than hydronium ions in water. This rate enhancement is not related to a shift in mechanism; for both cases, the dehydration of cyclohexanol occurs via an E1 mechanism with the cleavage of Cβ–H bond being rate determining. The higher activity of hydronium ions in zeolites is caused by the enhanced association between the hydronium ion and the alcohol, as well as a higher intrinsic rate constant in the constrained environments compared with water. The higher rate constant is caused by a greater entropy of activation rather than a lower enthalpy of activation. These insights should allow us to understand and predict similar processes in confined spaces.

Theoretical investigation of the thermal decomposition of imidazolium ionic liquids with different halides ions

The ionic liquids (ILs) are green solvents with numerous applications in technology and science. Among the physical properties of the ILs which have a great effect on their application, thermal stability is an important issue which has been discussed in this paper. Kinetics aspect of thermal decomposition of the ILs is considered as a scale of thermal stability. The ILs which have been studied here are composed of 1-hexyl-3-methylimidazolium cation with halide anion [Hmim][X], (X=F, Cl, Br). Three probable paths for thermal decomposition of ILs have been proposed. The first and second paths are the SN2 mechanism in which there are two possible sites on the imidazolium ring position, methyl and hexyl chain. Third path is E2 mechanism which is initiated from hexyl chain. In the case of [Hmim][X] (X=Cl, Br), since the first path has a lower activation energy, it occurs faster than the second path, while in the case of [Hmim][F], path B has a lower barrier than path A and occurs faster. Energy analysis for three studied ILs, showed that [Hmim][Br] with Ea=137.5kJmol−1 is decomposed faster than other ILs.

Kinetic and quantum chemical studies of the mechanism of dehydrochlorination of 2,2-diaryl-1,1,1-trichloroethanes with nitrite ions

The E2 mechanism has been proposed for the dehydrochlorination of 2,2-diaryl-1,1,1-trichloroethanes with nitrite ion, leading to 2,2-diaryl-1,1-dichloroethenes, on the basis of experimental kinetic study and quantum chemical simulation.

Site-Directed Chemical Mutations on Abzymes: Large Rate Accelerations in the Catalysis by Exchanging the Functionalized Small Nonprotein Components.

Taking advantage of antibody molecules to generate tailor-made binding sites, we propose a new class of protein modifications, termed as "site-directed chemical mutation." In this modification, chemically synthesized catalytic components with a variety of steric and electronic properties can be noncovalently and nongenetically incorporated into specific sites in antibody molecules to induce enzymatic activity. Two catalytic antibodies, 25E2 and 27C1, possess antigen-combining sites which bind catalytic components and act as apoproteins in catalytic reactions. By simply exchanging these components, antibodies 25E2 and 27C1 can catalyze a wide range of chemical transformations including acyl-transfer, β-elimination, aldol, and decarboxylation reactions. Although both antibodies were generated with the same hapten, phosphonate diester 1, they showed different catalytic activity. When phenylacetic acid 4 was used as the catalytic component, 25E2 efficiently catalyzed the elimination reaction of β-haloketone 2, whereas 27C1 showed no catalytic activity. In this work, we focused on the β-elimination reaction and examined the site-directed chemical mutation of 27C1 to induce activity and elucidate the catalytic mechanism. Molecular models showed that the cationic guanidyl group of ArgH52 in 27C1 makes a hydrogen bond with the P═O oxygen in the hapten. This suggested that during β-elimination, ArgH52 of 27C1 would form a salt bridge with the carboxylate of 4, thus destroying reactivity. Therefore, we utilized site-directed chemical mutation to change the charge properties of the catalytic components. When amine components 7-10 were used, 27C1 efficiently catalyzed the β-elimination reaction. It is noteworthy that chemical mutation with secondary amine 8 provided extremely high activity, with a rate acceleration [(kcat/Km 2)/kuncat] of 1 000 000. This catalytic activity likely arises from the proximity effect, plus general-base catalysis associated the electrostatic interactions. In 27C1, the cationic guanidyl group of ArgH52 is spatially close to the nitrogen of the amine components. In this microenvironment, the intrinsic pKa of the amine is perturbed and shifts to a lower pKa, which efficiently abstracts the α-proton during the reaction. This mechanism is consistent with the observed kinetic isotope effect (E2 or E1cB mechanism). Thus, site-directed chemical mutation provides a better understanding of enzyme functions and opens new avenues in biocatalyst research.

Cyclin E as a potential therapeutic target in high grade serous ovarian cancer

Cyclin E1 (CCNE1) gene amplification occurs in approximately 20% of ovarian high grade serous carcinoma (HGSC) and is associated with chemotherapy resistance and, in some studies, overall poor prognosis. The role of cyclin E1 in inducing S phase entry relies upon its interactions with cyclin dependent kinases (CDK), specifically CDK2. Therapies to target cyclin E1-related functions have centered on CDK inhibitors and proteasome inhibitors. While many studies have helped elucidate the functions and regulatory mechanisms of cyclin E1, further research utilizing cyclin E1 as a therapeutic target in ovarian cancer is warranted. This review serves to present the scientific background describing the role and function of cyclin E1 in cancer development and progression, to distinguish cyclin E1-amplified HGSC as a unique subset of ovarian cancer deserving of further therapeutic investigation, and to provide an updated overview on the studies which have utilized cyclin E1 as a target for therapy in ovarian cancer.

17β-Estradiol mediates superior adaptation of right ventricular function to acute strenuous exercise in female rats with severe pulmonary hypertension.

17β-Estradiol (E2) exerts protective effects on right ventricular (RV) function in pulmonary arterial hypertension (PAH). Since acute exercise-induced increases in afterload may lead to RV dysfunction in PAH, we sought to determine whether E2 allows for superior RV adaptation after an acute exercise challenge. We studied echocardiographic, hemodynamic, structural, and biochemical markers of RV function in male and female rats with sugen/hypoxia (SuHx)-induced pulmonary hypertension, as well as in ovariectomized (OVX) SuHx females, with or without concomitant E2 repletion (75 μg·kg(-1)·day(-1)) immediately after 45 min of treadmill running at 75% of individually determined maximal aerobic capacity (75% aerobic capacity reserve). Compared with males, intact female rats exhibited higher stroke volume and cardiac indexes, a strong trend for better RV compliance, and less pronounced increases in indexed total pulmonary resistance. OVX abrogated favorable RV adaptations, whereas E2 repletion after OVX markedly improved RV function. E2's effects on pulmonary vascular remodeling were complex and less robust than its RV effects. Postexercise hemodynamics in females with endogenous or exogenous E2 were similar to hemodynamics in nonexercised controls, whereas OVX rats exhibited more severely altered postexercise hemodynamics. E2 mediated inhibitory effects on RV fibrosis and attenuated increases in RV collagen I/III ratio. Proapoptotic signaling, endothelial nitric oxide synthase phosphorylation, and autophagic flux markers were affected by E2 depletion and/or repletion. Markers of impaired autophagic flux correlated with endpoints of RV structure and function. Endogenous and exogenous E2 exerts protective effects on RV function measured immediately after an acute exercise challenge. Harnessing E2's mechanisms may lead to novel RV-directed therapies.

The Super-Relaxed State of Myosin is Altered by Estradiol in Skeletal Muscle of Aged Female Mice

We have used quantitative epifluorescence microscopy of fluorescent ATP to measure single-nucleotide turnover in skinned skeletal muscle fibers from old male and female mice. Aging causes declines in muscle strength, often leading to weakness-related health problems for the elderly. Female muscle has additional functional decrements with age due to reduced ovarian hormone production. Estradiol (E2) is the major sex hormone signal to skeletal muscle in females, and strength loss is rescued by E2 treatment in ovariectomized (OVX) mice. We previously showed that E2-mediated signaling reversibly regulates slow ATP turnover by myosin in single fibers isolated from OVX mice. To investigate E2 mechanisms on aged skeletal muscle, single fibers were isolated from young (2 months) or old (28 months) male and female mice, and were incubated with mantATP. Old female mice receiving 60-day E2 treatment were also studied. We measured the decay of mantATP fluorescence in an ATP-chase experiment to characterize the slow nucleotide turnover, called the super-relaxed state (SRX), detected in approximately one-third of the myosin heads. The SRX turnover was faster in aged female fibers compared to young female fibers. In contrast, ATP turnover in old male fibers was not significantly different than in young males, and even trended toward slower rather than faster turnover with aging. We conclude that E2-mediated signaling reversibly regulates slow ATP turnover by myosin in aging female mice. Age- and hormone-related functional deficits may be targetable at the level of myosin and other contractile protein structure/function for strategies to offset muscle weakness and metabolic changes that occur with age. This work was supported by NIH grants to DDT (R37 AG026160 and R01 AR032961), to DL (R01 AG31743), to BAC (R00 HL122397), and to KJP and BCC (T32 AR7612).

HPTLC-profiling of eleutherosides, mechanism of antioxidative action of eleutheroside E1, the PAMPA test with LC/MS detection and the structure-activity relationship.

Human body is constantly generating free radicals, which causes oxidative stress. Despite naturally occurring antioxidant systems in human body, free radicals cause lipid, proteins and DNA oxidation. New antioxidants are still urgent as well as their mechanisms of action should be explained. In this study, we investigated the mechanism by which eleutherosides B, E and E1 may act as antioxidants, identified eleutherosides in Eleutherococcus lasiogyne and Eleutherococcus giraldii, and explained in vitro the absorption of eleutheroside E1 based on passive transport. The DPPH∗ and DB-HPTLC tests were used to assess the antioxidant activity. Of the three eleutherosides, only eleutheroside E1 exhibited a strong anti-DPPH∗ activity (EC50 37.03 μg/mL; 63 mMol) compared to the raw extracts (EC50 170 and 180 μg/mL for E. lasiogyne and E. giraldii). This activity was also confirmed by the DB-HPTLC autography technique. According to Załuski’s hypothesis, the antioxidant mechanism of eleutheroside E1 is based on the complexation of DPPH∗ molecule with its aryl radical. During this reaction, the aryl radical of eleutheroside E1 (E1∗) and DPPHH are created. Next, the aryl radical (E1∗) is complexed with another DPPH∗ molecule. Additionally, the aryl radical can be stabilized by the presence of the methoxy groups in the aromatic ring, which increases its antioxidative action. The HPTLC-identification of extracts showed the presence of eleutherosides B, E and E1 in both species. The PAMPA test coupled with LC/MS detection showed a low permeability of eleutheroside E1 across artificial membrane. Because eleutherosides belong to the polyphenols, the TPC and TFC were quantified. The TPC and TFC varied from 51.4 to 49.3 mg/g dry extract for TPC, and from 5.73 to 4.91 mg/g dry extract for TFC, for E. giraldii and E. lasiogyne, respectively. In conclusion, eleutheroside E1 in its pure form could be a chemopreventive ingredient of new pharmacological or dietary products, stimulating the GALT. These findings can explain partially the adaptogenic activity of eleutheroside E1 on the GALT, which has been still unknown.

Mechanisms and energetics for N-glycosidic bond cleavage of protonated 2'-deoxyguanosine and guanosine.

Experimental and theoretical investigations suggest that hydrolysis of N-glycosidic bonds generally involves a concerted SN2 or a stepwise SN1 mechanism. While theoretical investigations have provided estimates for the intrinsic activation energies associated with N-glycosidic bond cleavage reactions, experimental measurements to validate the theoretical studies remain elusive. Here we report experimental investigations for N-glycosidic bond cleavage of the protonated guanine nucleosides, [dGuo+H](+) and [Guo+H](+), using threshold collision-induced dissociation (TCID) techniques. Two major dissociation pathways involving N-glycosidic bond cleavage, resulting in production of protonated guanine or the elimination of neutral guanine are observed in competition for both [dGuo+H](+) and [Guo+H](+). The detailed mechanistic pathways for the N-glycosidic bond cleavage reactions observed are mapped via electronic structure calculations. Excellent agreement between the measured and B3LYP calculated activation energies and reaction enthalpies for N-glycosidic bond cleavage of [dGuo+H](+) and [Guo+H](+) in the gas phase is found indicating that these dissociation pathways involve stepwise E1 mechanisms in analogy to the SN1 mechanisms that occur in the condensed phase. In contrast, MP2 is found to significantly overestimate the activation energies and slightly overestimate the reaction enthalpies. The 2'-hydroxyl substituent is found to stabilize the N-glycosidic bond such that [Guo+H](+) requires ∼25 kJ mol(-1) more than [dGuo+H](+) to activate the glycosidic bond.

Computational Study of Ethanol Conversion on Al8O12 as a Model for γ-Al2O3

Correlated molecular orbital theory at the coupled cluster CCSD(T) level with density functional theory geometries is used to study ethanol dehydration, dehydrogenation, and condensation reactions on an the Al8O12 cluster which is a model for γ-Al2O3. The Al in the active site on the cluster is a strong Lewis acid. The reactions begin with formation of a very stable Lewis acid–base ethanol–cluster adduct. Dehydration proceeds by β-H transfer to a bicoordinate oxygen leading to the direct formation of ethylene and two OH groups following an E2 mechanism. Dehydrogenation proceeds directly by α-H transfer to the active metal center and a proton transfer to a bicoordinate bridge O to form acetaldehyde plus a metal hydride and a hydroxyl, again an E2 mechanism. After addition of a second ethanol, diethyl ether is generated by an α-C transfer from the first to the second ethanol, an acid-driven SN2 mechanism. Condensation and dehydration with two alcohols have comparable energy barriers. The addition of a secon...

The Proline Enamine Formation Pathway Revisited in Dimethyl Sulfoxide: Rate Constants Determined via NMR

Enamine catalysis is a fundamental activation mode in organocatalysis and can be successfully combined with other catalytic methods, e.g., photocatalysis. Recently, the elusive enamine intermediates were detected, and their stabilization modes were revealed. However, the formation pathway of this central organocatalytic intermediate is still a matter of dispute, and several mechanisms involving iminium and/or oxazolidinone are proposed. Here, the first experimentally determined rate constants and rates of enamine formation are presented using 1D selective exchange spectroscopy (EXSY) buildup curves and initial rate approximation. The trends of the enamine formation rates from exo-oxazolidinones and endo-oxazolidinones upon variation of the proline and water concentrations as well as the nucelophilic/basic properties of additives are investigated together with isomerization rates of the oxazolidinones. These first kinetic data of enamine formations in combination with theoretical calculations reveal the deprotonation of iminium intermediates as the dominant pathway in dimethyl sulfoxide (DMSO). The dominant enamine formation pathway varies according to the experimental conditions, e.g., the presence and strength of basic additives. The enamine formation is zero-order in proline and oxazolidinones, which excludes the direct deprotonation of oxazolidinones via E2 mechanism. The nucleophilicity of the additives influences only the isomerization rates of the oxazolidinones and not the enamine formation rates, which excludes a nucleophile-assisted anti elimination of oxazolidinones as a major enamine formation pathway.

Highly selective gas-phase synthesis of 1,1-dichloroethylene from 1,1,2-trichloroethane over supported amine catalysts

The manufacture of 1,1-dichloroethylene(1,1-DCE) usually employs liquid phase method to perform the dehydrochlorination of 1,1,2-trichloroethane(TCE), where large amounts of high-concentration salty wastewater is produced inevitably. It has been a long-term goal to achieve the gas phase synthesis of 1,1-DCE via supported catalysts. In this work, the gas-phase synthesis of 1,1-DCE from TCE was studied in the presence of pentaethylenehexamine( PEHA) supported on silica. High and stable selectivity to 1,1-DCE(up to 98%) was obtained, which could be ascribed to the relatively strong basicity of PEHA according to a proposed E2 mechanism. The formation of PEHA chloride from the HCl generated in situ was detected and was considered to be the main reason for the deactivation of PEHA catalyst.

Influence of operating parameters on the fate and removal of three estrogens in a laboratory-scale AAO system.

A laboratory-scale anaerobic-anoxic-oxic (AAO) process was constructed to investigate the influence of hydraulic residence time (HRT) and sludge retention time (SRT) on the removal and fate of estrone (E1), 17β-estradiol (E2) and 17α-ethinylestradiol (EE2), and their removal mechanisms in a biological treatment system. In an HRT range of 5-15 h, the highest removal efficiencies for E1, E2 and EE2 were obtained at an HRT of 8 h, with values of 91.2, 94.6 and 81.5%, respectively. When the SRT was increased from 10 to 20 d, all three estrogen removal efficiencies stayed above 80%, while the optimal SRT for each estrogen was different. The contribution of each tank for removal of the three estrogens was in the order of aerobic tank>anoxic tank>anaerobic tank. The optimal HRT and SRT for the removal of both the three estrogens and nutrients were 8 h and 15d, respectively. At this condition, respectively, about 50.7, 70.1 and 11.3% of E1, E2 and EE2 were biodegraded, 28.8, 17.2 and 50% were accumulated in the system, 8.3, 5.4 and 17.3% were discharged in the effluent, and 12.2, 7.3 and 20.34% were transported into excess sludge. It indicated that biodegradation by sludge microorganisms was the main removal mechanism of E1 and E2, while adsorption onto sludge was the main mechanism for EE2 removal.

DFT-driven multi-site microkinetic modeling of ethanol conversion to ethylene and diethyl ether on γ-Al2O3(1 1 1)

We investigate the γ-Al2O3-catalyzed production of ethylene and diethyl ether from ethanol in a combined density functional theory (DFT) and microkinetic modeling study. DFT calculations on the γ-Al2O3(111) surface facet demonstrate that the energetically favorable pathway for ethylene formation is an E2 mechanism (Ea=28kcal/mol), while ether formation takes place via a bimolecular (SN2) mechanism (Ea=32kcal/mol). The DFT-parameterized two-site mean-field microkinetic model successfully captures trends in experimentally measured reaction orders. Microkinetic analysis indicates that the SN2 and E2 elementary steps control the overall rate. Analytical rate expressions are derived from the full microkinetic model and fit to experimental data, capturing reaction order trends with similar success as the full model. The outcome of the fitting suggests that an additional active site may be responsible for some ethanol conversion. The success of the models demonstrates the applicability of the DFT-computed mechanisms to powdered γ-Al2O3 catalysts.

Non-invasive administration of 17β-estradiol rapidly increases aggressive behavior in non-breeding, but not breeding, male song sparrows

17β-Estradiol (E2) acts in the brain via genomic and non-genomic mechanisms to influence physiology and behavior. There is seasonal plasticity in the mechanisms by which E2 activates aggression, and non-genomic mechanisms appear to predominate during the non-breeding season. Male song sparrows (Melospiza melodia) display E2-dependent territorial aggression throughout the year. Field studies show that song sparrow aggression during a territorial intrusion is similar in the non-breeding and breeding seasons, but aggression after an intrusion ends differs seasonally. Non-breeding males stop behaving aggressively within minutes whereas breeding males remain aggressive for hours. We hypothesize that this seasonal plasticity in the persistence of aggression relates to seasonal plasticity in E2 signaling. We used a non-invasive route of E2 administration to compare the non-genomic (within 20min) effects of E2 on aggressive behavior in captive non-breeding and breeding season males. E2 rapidly increased barrier contacts (attacks) during an intrusion by 173% in non-breeding season males only. Given that these effects were observed within 20min of E2 administration, they likely occurred via a non-genomic mechanism of action. The present data, taken together with past work, suggest that environmental cues associated with the non-breeding season influence the molecular mechanisms through which E2 influences behavior. In song sparrows, transient expression of aggressive behavior during the non-breeding season is highly adaptive: it minimizes energy expenditure and maximizes the amount of time available for foraging. In all, these data suggest the intriguing possibility that aggression in the non-breeding season may be activated by a non-genomic E2 mechanism due to the fitness benefits associated with rapid and transient expression of aggression.