Oxidative Conditions Research Articles

Exploiting G-Quadruplex-DNA Damage as a Tool to Quantify Singlet Oxygen Production.

G-Quadruplexes (G4s) are highly dynamic and polymorphic nucleic acid structures that can adopt a variety of conformations. When exposed to oxidative conditions, more specifically singlet oxygen, the guanosine nucleobases can be oxidized, which in turn can affect the conformation and folding of the G4. Based on this peculiar phenomenon, it is rationalized that G4s can serve as quantification sensors for the production of singlet oxygen. Here, a method for determining the quantum yield of singlet oxygen generation for visible as well as UV-light excited photosensitizers, using a short G4 DNA sequence, readily available from common DNA companies, as a biological and water-soluble probe, is presented.

Biomimetic Vesicles with Designer Phospholipids Can Sense Environmental Redox Cues.

Cell-like materials that sense environmental cues can serve as next-generation biosensors and help advance the understanding of intercellular communication. Currently, bottom-up engineering of protocell models from molecular building blocks remains a grand challenge chemists face. Herein, we describe giant unilamellar vesicles (GUVs) with biomimetic lipid membranes capable of sensing environmental redox cues. The GUVs employ activity-based sensing through designer phospholipids that are fluorescently activated in response to specific reductive (hydrogen sulfide) or oxidative (hydrogen peroxide) conditions. These synthetic phospholipids are derived from 1,2-dipalmitoyl-rac-glycero-3-phosphocholine and they possess a headgroup with heterocyclic aromatic motifs. Despite their structural deviation from the phosphocholine headgroup, the designer phospholipids (0.5-1.0 mol %) mixed with natural lipids can vesiculate, and the resulting GUVs (7-20 μm in diameter) remain intact over the course of redox sensing. All-atom molecular dynamics simulations gave insight into how these lipids are positioned within the hydrophobic core of the membrane bilayer and at the membrane-water interface. This work provides a purely chemical method to investigate potential redox signaling and opens up new design opportunities for soft materials that mimic protocells.

Regeneration of copper catalysts mediated by molybdenum-based oxides

Cu catalysts, known for their unparalleled catalytic capabilities due to their unique electronic structure, have faced inherent challenges in maintaining long-term effectiveness under harsh hydrogenation conditions. Here, we demonstrate a molybdenum-mediated redispersion behavior of Cu under high-temperature oxidation conditions. The oxidized Cu nanoparticles with rich metal-support interfaces tend to dissolve into the MoO3 support upon heating to 600 °C, which facilitates the subsequent regeneration in a reducing atmosphere. A similar redispersion phenomenon is observed for Cu nanoparticles supported on ZnO-modified MoO3. The modification of ZnO significantly improves the performance of the Cu catalyst for CO2 hydrogenation to methanol, with the high activity being well maintained after four repeated oxidation-reduction cycles. In situ spectroscopic and theoretical analyses suggest that the interaction involved in the formation of the copper molybdate-like compound is the driving force for the redispersion of Cu. This method is applicable to various Mo-based oxide supports, offering a practical strategy for the regeneration of sintered Cu particles in hydrogenation applications.

Fluid inclusions in quartz of the gold-ore occurrences and gold-quartz intergrowths from placers in the Sololi uplift of the Olenyok arch (Yakutia)

Fluid inclusions have been studied in vein quartz with gold sulfide mineralization from metamorphosed sandstones of the Eekite series and metarhyolites of the Early Proterozoic, in quartz breccia from the zone of overlapping gold mineralization on the Early and Middle Permian sandstones, as well as in the gold quartz intergrowths from the Sololi River placer. It has been revealed that formation of quartz breccias occurred within a wide temperature interval from 230 to 425 ºC, with predominance of carbon dioxide and nitrogen in the vapor phase. It is suggested that the increased nitrogen content may be associated with a chemical reaction between the fluid and ammonium-containing silicates of host rocks, in which nitrogen in the form of NH4+ isomorphically replaces potassium at the regressive stage of metamorphism. At the same time, it is possible that mantle nitrogen, which was transported along the Anabar-Eekite deep fault, participated in formation of the studied breccias. The close homogenization temperatures and similar nature of the water-salt composition for the fluid inclusions of quartz veins that inject the Eekite series meta-rocks and meta-rhyolites indicate the synchronism of their formation and attribute them to the common stage of ore formation. Quartz veins with gold sulfide mineralization were the primary sources of pebbles with gold-quartz intergrowths from the Sololi River, this is evidenced by similarity of principal characteristics of fluid inclusions. Oxidizing conditions of the mineralization serve as favorable factor for the Au deposition, it is indicated by the predominant CO2 content in fluid inclusions, keeping role of a geochemical barrier and leading to an elevated gold content in quartz veins.

Efficient aerobic and DMSO-oxidative sulfenylation reactions catalyzed by Na2S2O3

Two efficient acid-base-free procedures are introduced for the sulfenylation of cyclic enaminone compounds under aerobic and DMSO-oxidative conditions catalyzed by Na2S2O3. According to procedures, a mixture of an aryl thiol and a cyclic enaminone are reacting together in DMF (aerobic oxidative conditions) or DMSO in the presence of a catalytic amount of Na2S2O3 (0.1 equiv in DMSO and 0.4 equiv in DMF) to produce the related α-sulfenylated cyclic enaminone compound in high yields. Both reactions are not satisfactory in the absence of Na2S2O3, so the reaction in DMF (aerobic condition) does not produce any product at all and the conversion in DMSO progresses by less than 50% within 24 h.

Intelligent salivary biosensors for periodontitis: in vitro simulation of oral oxidative stress conditions.

One of the most common oral diseases affecting millions of people worldwide is periodontitis. Usually, proteins in body fluids are used as biomarkers of diseases. This study focused on hydrogen peroxide, lipopolysaccharide (LPS), and lactic acid as salivary non-protein biomarkers for oxidative stress conditions of periodontitis. Electrochemical analysis of artificial saliva was done using Gamry with increasing hydrogen peroxide, bLPS, and lactic acid concentrations. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were conducted. From EIS data, change in capacitance and CV plot area were calculated for each test condition. Hydrogen peroxide groups had a decrease in CV area and an increase in percentage change in capacitance, lipopolysaccharide groups had a decrease in CV area and a decrease in percentage change in capacitance, and lactic acid groups had an increase of CV area and an increase in percentage change in capacitance with increasing concentrations. These data showed a unique combination of electrochemical properties for the three biomarkers. Scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) employed to observe the change in the electrode surface and elemental composition data present on the sensor surface also showed a unique trend of elemental weight percentages. Machine learning models using hydrogen peroxide, LPS, and lactic acid electrochemical data were applied for the prediction of risk levels of periodontitis. The detection of hydrogen peroxide, LPS, and lactic acid by electrochemical biosensors indicates the potential to use these molecules as electrochemical biomarkers and use the data for ML-driven prediction tool for the periodontitis risk levels.

Crystal Structure Regulation of CoSe2 Induced by Fe Dopant for Promoted Surface Reconstitution toward Energetic Oxygen Evolution Reaction.

Most nonoxide catalysts based on transition metal elements will inevitably change their primitive phases under anodic oxidation conditions in alkaline media. Establishing a relationship between the bulk phase and surface evolution is imperative to reveal the intrinsic catalytic active sites. In this work, it is demonstrated that the introduction of Fe facilitates the phase transition of orthorhombic CoSe2 into its cubic counterpart and then accelerates the Co-Fe hydroxide layer generation on the surface during electrocatalytic oxygen evolution reaction (OER). As a result, the Fe-doped cubic CoSe2 catalyst exhibits a significantly enhanced activity with a considerable overpotential decrease of 79.9 and 66.9 mV to deliver 10 mA·cm-2 accompanied by a Tafel slope of 48.0 mV·dec-1 toward OER when compared to orthorhombic CoSe2 and Fe-doped orthorhombic CoSe2, respectively. Density functional theory (DFT) calculations reveal that the introduction of Fe on the surface hydroxide layers will tune electron density around Co atoms and raise the d-band center. These findings will provide deep insights into the surface reconstitution of the OER electrocatalysts based on transition metal elements.

Catalytic atomic layer deposition of amorphous alumina–silica thin films on carbon microfibers

Deposition of silica-based thin films on carbon microfibers has long been considered a challenge. Indeed, the oxidation-sensitive nature of carbon microfibers over 550 K and their submicron-textured surface does not bode well with the required conformity of deposition best obtained by atomic layer deposition (ALD) and the thermal oxidative conditions associated with common protocols of silica ALD. Nonetheless, the use of a catalytic ALD process allowed for the deposition of amorphous alumina–silica bilayers from 445 K using trimethylaluminium and tris(tert-pentoxy)silanol (TPS). In this study, first undertaken on flat silicon wafers to make use of optical spectroscopies, the interplay between kinetics leading to a dense silica film growth was investigated in relation to the applied operation parameters. A threshold between the film catalyzed growth and the complete outgassing of pentoxy-derived compounds from TPS was found, resulting in a deposition of equivalent growth per cycle of 1.1 nm c−1, at a common ALD rate of 0.3 nm min−1, with a flat thickness gradient. The deposition on carbon microfiber fabrics was found conformal, albeit with a thickness growth capped below 20 nm, imparted by the microfiber surface texture. STEM-EDX showed a sharp interface of the bilayer with limited carbon diffusion. The conformal and dense deposition of alumina–silica thin films on carbon microfibers holds great potential for further use as refractory oxygen barrier layers.

Phenolic composition and in vitro bioactive and enzyme inhibitory properties of bell pepper (Capsicum annuum L.) plant extracts

The phenolic composition and bioactive properties of Holland and Italian bell pepper plant (Capsicum annuum L.) hydroethanolic extracts were investigated by HPLC-DAD-ESI/MS and in vitro cell- and enzyme-based assays, respectively. O-Glycosylated luteolin derivatives were identified as the major compounds, representing ∼60% of the phenolic fraction. Both extracts displayed remarkable antioxidant activity and ability to inhibit α-glucosidase and the formation of advanced glycation end products (AGEs) compared to the positive controls, which yielded statistically higher or equal IC50 values. Notably, the extracts were up to 57 times more effective than aminoguanidine in inhibiting AGEs. The lipase enzyme involved in fat metabolism and the pro-inflammatory mediator nitric oxide were also inhibited in some extent, with orlistat and dexamethasone being 10–13.4-fold and ∼17-fold more effective than the extracts, respectively. A notable cytotoxicity occurred on the tested human tumor cell lines, mainly on Caco-2 with GI50 values ranging from 18 to 65 μg/mL. Furthermore, activity greater than that of food preservatives was observed against some foodborne fungi and bacteria. These results highlight bell pepper plant by-products as a renewable source of functional ingredients that could be utilized in food, nutraceutical, and medicinal formulations to manage type 2 diabetes, obesity, and other oxidative stress-mediated conditions.

Effects of clove bud oil on the physicochemical properties and oxidative stability of canola oil organogels structured by different beeswax contents.

The aim of this study was to investigate the utilization of clove bud oil as fat-soluble antioxidants for retarding lipid oxidation in organogels by structuring canola oil with beeswax at 5, 7.5, and 10% concentration under accelerated oxidation condition. Oil binding capacity and viscoelastic properties were increased with beeswax content, but were not nearly affected by the addition of clove bud oil. Organogel loaded with clove bud oil were found to be more effective in retarding lipid oxidation in high beeswax content systems, particularly evident in 10% beeswax samples. The addition of clove bud oil resulted in low levels of hyeoperxide and MDA, and protected against texture and color deterioration during the storage period. Additionally, the Pearson correlation between lipid oxidation indices and parameters of texture and color has been found to exhibit a limited association, with the exception of the a* and b* values, which show a strong correlation.

The antioxidant effect of tetrahedral framework nucleic acid-based delivery of small activating RNA targeting DJ-1 on retinal oxidative stress injury.

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are the world's leading causes of blindness. The retinal pigment epithelium (RPE) and vascular endothelial cell exposed to oxidative stress is the major cause of AMD and DR. DJ-1, an important endogenous antioxidant, its overexpression is considered as a promising antioxidant treatment for AMD and DR. Here, we modified the tetrahedral frame nucleic acids (tFNAs) with DJ-1 saRNAs as a delivery system, and synthesized a novel nanocomplex (tFNAs-DJ-1 saRNAs). In vitro studies show that tFNAs-DJ-1 saRNAs can efficiently transfer DJ-1 saRNAs to human umbilical vein endothelial cells (HUVECs) and ARPE-19s, and significantly increased their cellular DJ-1 level. Reactive oxygen species expression in H2O2-treated HUVECs and ARPE-19s were decreased, cell viability was enhanced and cell apoptosis were inhibited when tFNAs-DJ-1 saRNAs were delivered. Moreover, tFNAs-DJ-1 saRNAs preserved mitochondrial structure and function under oxidative stress conditions. In the aspect of molecular mechanism, tFNAs-DJ-1 saRNAs activated Erk and Nrf2 pathway, which might contribute to its protective effects against oxidative stress damage. To conclude, this study shows the successfully establishment of a simple but effective delivery system of DJ-1 saRNAs associated with antioxidant effects in AMD and DR, which may be a promising agent for future treatment in oxidative stress-related retinal disorders.

Construction of porous micro/nano structures on the surface of Ti–Mo–Zr alloys by anodic oxidation for biomedical application

Ti–Mo–Zr alloys have attracted increasing interest for biomedical applications, due to their outstanding properties such as low elastic modulus. To improve the bioactivity of alloys, this study utilized the anodic oxidation method to fabricate porous micro/nano structures on the surface of a series of Ti–Mo–Zr alloys, including the Ti–12Mo-AO, Ti–10Zr-AO, and Ti–12Mo–10Zr-AO groups. The morphology, composition, phase, microhardness, roughness, wettability, adhesion strength, corrosion resistance, bioactivity, and biocompatibility of each group were systematically investigated. The formation mechanism of surfaces was discussed from the perspective of thermodynamics. Our results demonstrated that, Ti–12Mo-AO showed the structure of single-layer regularly arranged nanotubes, while Ti–10Zr-AO and Ti–12Mo–10Zr-AO exhibited a double-layer porous structure with a nano-filamentous upper layer and a densely arranged nanotube lower layer. With low crystallinity, these surfaces showed an amorphous structure and were composed of the oxides of corresponding matrix element. After anodizing, the microhardness and wettability of surfaces increased, while their corrosion resistance decreased. Compared with Ti–12Mo-AO, Ti–10Zr-AO and Ti–12Mo–10Zr-AO possessed a higher degree of roughness, better wettability, stronger interface bonding, and higher apatite forming ability. Furthermore, the biocompatibility of Ti–12Mo–10Zr-AO was superior to that of the other groups. Taken together, our results revealed that, under the same anodic oxidation condition, Ti–Mo–Zr alloys formed different porous micro/nano structures on the surface. Particularly, due to its favorable properties, Ti–12Mo–10Zr-AO is very attractive for future biomedical application.

The Selenoproteome as a Dynamic Response Mechanism to Oxidative Stress in Hydrogenotrophic Methanogenic Communities.

Methanogenesis is a critical process in the carbon cycle that is applied industrially in anaerobic digestion and biogas production. While naturally occurring in diverse environments, methanogenesis requires anaerobic and reduced conditions, although varying degrees of oxygen tolerance have been described. Microaeration is suggested as the next step to increase methane production and improve hydrolysis in digestion processes; therefore, a deeper understanding of the methanogenic response to oxygen stress is needed. To explore the drivers of oxygen tolerance in methanogenesis, two parallel enrichments were performed under the addition of H2/CO2 in an environment without reducing agents and in a redox-buffered environment by adding redox mediator 9,10-anthraquinone-2,7-disulfonate disodium. The cellular response to oxidative conditions is mapped using proteomic analysis. The resulting community showed remarkable tolerance to high-redox environments and was unperturbed in its methane production. Next to the expression of pathways to mitigate reactive oxygen species, the higher redox potential environment showed an increased presence of selenocysteine and selenium-associated pathways. By including sulfur-to-selenium mass shifts in a proteomic database search, we provide the first evidence of the dynamic and large-scale incorporation of selenocysteine as a response to oxidative stress in hydrogenotrophic methanogenesis and the presence of a dynamic selenoproteome.

Simultaneous Environmental Waste Management through Deep Dewatering of Alum Sludge Using Waste-Derived Cellulose

To simultaneously solve problems in an eco-friendly manner, introducing a waste residual as a sustainable conditioner to aid alum sludge dewatering is suggested as a cradle-to-cradle form of waste management. In this regard, the superiority of deep dewatering alum sludge with a powdered wood chip composite residual as a novel conditioner was explored, whereby traditional conventional conditioners, i.e., polyelectrolytes and lime, were substituted with powdered wood chips. Initially, Fe3O4 was prepared at the nanoscale using a simple co-precipitation route. Next, wooden waste was chemically and thermally treated to attain cellulosic fine powder. Subsequently, the resultant wood powder and Fe3O4 nanoparticles were mixed at 50 wt % to attain a wood powder augmented with iron, and this conditioner was labeled nano-iron-cellulose (nIC-Conditioner). This material (nIC-Conditioner) was mixed with hydrogen peroxide to represent a dual oxidation and skeleton builder conditioning substance. Characterization of the resultant conditioner was carried out using transmission electron microscopy (TEM) and Fourier transform infrared (FT-IR) transmittance spectrum analysis. The feasibility of the experimental results revealed that the moisture content in the sludge cake was lower after conditioning, and the capillary suction time (CST) was reduced to 78% compared to that of raw alum sludge after 5 min of dewatering time. Moreover, the optimal system parameters, including nIC-Conditioner and H2O2 concentrations, as well as the working pH, were optimized, and optimal values were recorded at 1 g/L and 200 mg/L for nIC-Conditioner and H2O2, respectively, with a pH of 6.5. Additionally, scanning electron microscope (SEM) analyses of the sludge prior to and after conditioning were conducted to verify the change in sludge molecules due to this conditioning technique. The results of this study confirm the sustainability of an alum sludge and waste management facility.

Oxidant-Assisted Sulfonylation/Cyclization Cascade Synthesis of Alkylsulfonylated Oxindoles via the Insertion of SO2.

An oxidant-assisted tandem sulfonylation/cyclization of electron-deficient alkenes with 4-alkyl-substituted Hantzsch esters and Na2S2O5 for the preparation of 3-alkylsulfonylated oxindoles under mild conditions in the absence of a photocatalyst and transition metal catalyst is established. The mechanism studies show that the alkyl radicals, which come from the cleavage of the C-C bond in 4-substituted Hantzsch esters under oxidant conditions, subsequently undergo the in situ insertion of sulfur dioxide to generate the crucial alkylsulfonyl radical intermediates. This three-component reaction provides an efficient and facile route for the construction of alkylsulfonylated oxindoles and avoids the use of highly toxic alkylsulfonyl chlorides or alkylsulfonyl hydrazines as alkylsulfonyl sources.

Synergistic interplay between melatonin and hydrogen sulfide enhances cadmium-induced oxidative stress resistance in stock (Matthiola incana L.)

ABSTRACT Ornamental crops particularly cut flowers are considered sensitive to heavy metals (HMs) induced oxidative stress condition. Melatonin (MLT) is a versatile phytohormone with the ability to mitigate abiotic stresses induced oxidative stress in plants. Similarly, signaling molecules such as hydrogen sulfide (H2S) have emerged as potential options for resolving HMs related problems in plants. The mechanisms underlying the combined application of MLT and H2S are not yet explored. Therefore, we evaluated the ability of individual and combined applications of MLT (100 μM) and H2S in the form of sodium hydrosulfide (NaHS), a donor of H2S, (1.5 mM) to alleviate cadmium (Cd) stress (50 mg L−1) in stock (Matthiola incana L.) plants by measuring various morpho-physiological and biochemical characteristics. The results depicted that Cd-stress inhibited growth, photosynthesis and induced Cd-associated oxidative stress as depicted by excessive ROS accumulation. Combined application of MLT and H2S efficiently recovered all these attributes. Furthermore, Cd stress-induced oxidative stress markers including electrolyte leakage, malondialdehyde, and hydrogen peroxide are partially reversed in Cd-stressed plants by MLT and H2S application. This might be attributed to MLT or H2S induced antioxidant plant defense activities, which effectively reduce the severity of oxidative stress indicators. Overall, MLT and H2S supplementation, favorably regulated Cd tolerance in stock; yet, the combined use had a greater effect on Cd tolerance than the independent application.

Uncovering the roles of Mycobacterium tuberculosis melH in redox and bioenergetic homeostasis: implications for antitubercular therapy.

This study unveils the pivotal role played by the melH gene in Mycobacterium tuberculosis and in Mycobacterium marinum in combatting the detrimental impact of oxidative conditions during infection. This investigation revealed notable alterations in the level of cytokinin-associated aldehyde, para-hydroxybenzaldehyde, as well as the redox buffer ergothioneine, upon deletion of melH. Moreover, changes in crucial cofactors responsible for electron transfer highlighted melH's crucial function in maintaining a delicate equilibrium of redox and bioenergetic processes. MelH prefers epoxide small substrates with a phenyl substituted substrate. These findings collectively emphasize the potential of melH as an attractive target for the development of novel antitubercular therapies that sensitize mycobacteria to host stress, offering new avenues for combating tuberculosis.

Simultaneous Estimation and Stability Indicating Method of Vildagliptin And Dapagliflozin by RP-HPLC in Pharmaceutical Dosage Form

Vildagliptin and Dapagliflozin drugs are used for the management of diabetes.The primary objective of the proposed research was to develop and validate analytical methods for simultaneous quantification of vildagliptin and dapagliflozin in pharmaceutical dosage form. Both the drugs were subjected to force degradation to ensure stability of pharmaceutical products. The HPLC method development was carried out on C18 column (250mm*4.6mm,5µm particle size). The chromatographic separation was achieved by isocratic mode with a mixture of Methanol: 0.01% Trifluoro acetic acid (pH-2.78) in the ratio of 95:05 % v/v as mobile phase. Flow rate was kept at 0.8 ml/min and selected wavelength for estimation was 210 nm. Stress testing with acid, alkaline, oxidative and thermal degradation was performed. The retention time was found to be 2.282 min and 4.070 min for vildagliptin and dapagliflozin, respectively. The drugs response found to be linear with correlation coefficient value was nearly 0.999 for vildagliptin and dapagliflozin with linearity range of 10 – 60 µg/ml. The recoveries from studies were found to be 99.78% and 100.17% for vildagliptin and dapagliflozin respectively. LOD and LOQ were found to be lower, hence the method proved sensitivity. Method was validated as per ICH guideline Q2(R1). Drugs had shown more degradation in oxidative condition, 10.62% and 13.52% for vildagliptin and dapagliflozin, respectively. The proposed method would be successfully applied for the stability indicating, impurity separation, qualitative and quantitative estimation of vildagliptin and dapagliflozin in pharmaceutical dosage form and in process quality control analysis.

Competing Mechanisms in Palladium-Catalyzed Alkoxycarbonylation of Styrene.

Palladium-catalyzed carbonylation is a versatile method for the synthesis of various aldehydes, esters, lactones, or lactams. Alkoxycarbonylation of alkenes with carbon monoxide and alcohol produces either saturated or unsaturated esters as a result of two distinct catalytic cycles. The existing literature presents an inconsistent account of the procedures favoring oxidative carbonylation products. In this study, we have monitored the intermediates featured in both catalytic cycles of the methoxycarbonylation of styrene PhCH=CH2 as a model substrate, including all short-lived intermediates, using mass spectrometry. Comparing the reaction kinetics of the intermediates in both cycles in the same reaction mixture shows that the reaction proceeding via alkoxy intermediate [PdII]-OR, which gives rise to the unsaturated product PhCH=CHCO2Me, is faster. However, with an advancing reaction time, the gradually changing reaction conditions begin to favor the catalytic cycle dominated by palladium hydride [PdII]-H and alkyl intermediates, affording the saturated products PhCH2CH2CO2Me and PhCH(CO2Me)CH3 preferentially. The role of the oxidant proved to be crucial: using p-benzoquinone results in a gradual decrease of the pH during the reaction, swaying the system from oxidative conditions toward the palladium hydride cycle. By contrast, copper(II) acetate as an oxidant guards the pH within the 5-7 range and facilitates the formation of the alkoxy palladium complex [PdII]-OR, which favors the oxidative reaction producing PhCH=CHCO2Me with high selectivity. Hence, it is the oxidant, rather than the catalyst, that controls the reaction outcome by a mechanistic switch. Unraveling these principles broadens the scope for developing alkoxycarbonylation reactions and their application in organic synthesis.

Programmed Heterocycle Synthesis Using Halomucononitriles as Pyridinimine Precursors.

Herein we report a method to convert primary amines, ubiquitous motifs found in pharmaceutical libraries, to either imidazo[1,2-a]pyridines or 7-alkyl azaindoles in two steps from known compounds. Using halomucononitrile reagents, we can directly access 5-bromo-6-imino-1-alkyl-1,6-dihydropyridine-2-carbonitriles (pyridinimines) in a single step from primary amines (25-93% yield) through the cyclization of transient aminomucononitrile intermediates. We then demonstrate that these compounds can be readily converted to 7-alkylazaindoles using Sonogashira cross-coupling conditions (13 examples, up to 91% yield). Under oxidative conditions, the pyridinimines serve as directing groups for C-H functionalization reactions to afford imidazo[1,2-a]pyridines. We also studied the mechanism of the cyclization event using DFT calculations and propose that this takes place via sequential base-mediated E/Z isomerization and cyclization steps.