Low Molecular Weight Compounds Research Articles

Chemical Adjustment of Fibrinolysis.

Fibrinolysis is the process of the fibrin-platelet clot dissolution initiated after bleeding has been stopped. It is regulated by a cascade of proteolytic enzymes with plasmin at its core. In pathological cases, the balance of normal clot formation and dissolution is replaced by a too rapid lysis, leading to bleeding, or an insufficient one, leading to an increased thrombotic risk. The only approved therapy for emergency thrombus lysis in ischemic stroke is recombinant tissue plasminogen activator, though streptokinase or urokinase-type plasminogen activators could be used for other conditions. Low molecular weight compounds are of great interest for long-term correction of fibrinolysis dysfunctions. Their areas of application might go beyond the hematology field because the regulation of fibrinolysis could be important in many conditions, such as fibrosis. They enhance or weaken fibrinolysis without significant effects on other components of hemostasis. Here we will describe and discuss the main classes of these substances and their mechanisms of action. We will also explore avenues of research for the development of new drugs, with a focus on the use of computational models in this field.

Investigating the role of hydrological connectivity on the processing of organic carbon in tropical aquatic ecosystems

Inland waters are highways of carbon and nutrient flows between the land and ocean. Aquatic environments integrate multiple sources and processes over space and time that influence ecosystem functionality. The complexity of these systems and their multiple interactions with the surrounding environment are conceptualised, but often lack empirical scrutiny that allows further understanding of how inland waters mobilise, transport, and utilise carbon and nutrients. This is particularly evident in tropical waters. Here, we apply advanced geochemical analyses of dissolved organic matter (DOM) composition in conjunction with algal pigment biomarkers, to determine the seasonal variability of organic matter production, processing and export for a tropical, floodpulse wetland, Tasik Chini (Malaysia). We identify two phases in the hydrological cycle: Phase 1 signifying a transition from the wet season with high suspended sediment and dissolved organic carbon concentrations. DOM is composed of humic substances, building blocks and lower molecular weight compounds. Towards the end this phase then are periods of increased water clarity and algal productivity. This is followed by Phase 2, which has a greater contribution of autochthonous DOM, composed of proteinaceous material, concomitant with lower dissolved nutrient concentrations, increased mixotrophic algae and emergent vegetation. Based on this framework, we highlight the role of such tropical wetland lakes as hydrological “bottlenecks,” through a lentic/lotic switch that shifts aquatic transport of carbon and nutrients from lateral river continuum supply to flood pulses. We highlight the need to consider inherent biases of spatial and temporal scaling when examining freshwater ecosystems along the land-ocean aquatic continuum.

Lysine-based non-cytotoxic ultrashort self-assembling peptides with antimicrobial activity.

Peptide-based molecules and their hydrogels are useful materials for biomedical applications due to the reversible nature of their self-assembly as well as the diversity of nanostructures that can be created starting from low-molecular weight compounds. In this study, we have focused on comprehending the characteristics of fibrillar networks of l-lysine-based self-assembled dipeptide hydrogels with a focus on their antibacterial properties. For that purpose, l-lysine has been complemented with hydrophobic aromatic moieties coming from l-phenylalanine and benzyloxyxarbonyl N-capping. In addition, the peptide C-terminus is blocked with alkylamides of different chain lengths which introduces additional dispersive interactions and hydrophobicity. These materials were well characterized by transmission electron microscopy, scanning electron microscopy, wide-angle powder X-ray diffraction and oscillatory rheology. Finally, biocompatibility and antimicrobial tests were performed showing that these hydrogels are compatible with HEK 293 cells and present a remarkable antibacterial activity against both Gram positive (S. aureus) and Gram negative (E. coli) bacteria.

The effect of histidine, histamine, and imidazole on electrochemical properties of Cu(II) complexes of Aβ peptides containing His-2 and His-3 motifs.

The N-truncation of amyloid beta (Aβ) peptides could lead to peptide sequences with the histidine residue at the second and third positions, creating His-2 and His-3 motifs, known as high-affinity Cu(II) binding sites. In such complexes, the Cu(II) ion is arrested in a rigid structure of a square-planar arrangement of nitrogen donors, which highly limits its susceptibility to Cu(II) reduction. Cu(II) reduction fuels the Cu(II)/Cu(I) redox cycle, which is engaged in the production of reactive oxygen species (ROS). Employing electrochemical techniques, cyclic voltammetry (CV) and differential pulse voltammetry (DPV), together with UV-vis spectroscopy, we showed that low-molecular-weight (LMW) substances, such as imidazole, histamine, and histidine, could enhance the redox activity of Cu(II) complexes of three models of N-truncated Aβ peptides, Aβ4-9, Aβ5-9, and Aβ12-16, identifying three main mechanisms. LMW compounds could effectively compete with Aβ peptides for Cu(II) ions, forming Cu(II)/LMW species, which are more prone to Cu(II) reduction. LMW substances could also shift the equilibrium between the Cu(II)/Aβ species towards the species with higher susceptibility to Cu(II) reduction. Finally, the presence of LMW molecules could promote Cu(I) reoxidation in ternary Cu(II)/Aβ/LMW systems. The obtained results raise further questions regarding the Cu(II) redox activity in Alzheimer's disease.

AVALIAÇÃO DA DEGRADAÇÃO TÉRMICA DO CAROÇO DE ABACATE RESIDUAL PARA A PRODUÇÃO DE BIOCARVÕES

EVALUATION OF THERMAL DEGRADATION OF RESIDUAL AVOCADO SEED FOR BIOCHAR PRODUCTION. The thermal degradation kinetics of avocado seed biomass (Persea americana) was investigated at the heating rates of 5, 15, 20 and 25 ºC min-1 using thermogravimetric (TGA) and differential thermogravimetric (DTG) analysis techniques in the temperature range from ambient to 780 ºC. Chemical analysis of the avocado seed resulted in: 51.4% cellulose, 42.4% hemicellulose, 20.1% lignin, 2.1% ash, 5.6% extractives. The pyrolysis products were characterized via FTIR, SEM/EDS. The isoconversional methods of Ozawa-Flynn-Wall (OFW) and Kissinger-Akahira-Sunose (KAS) have yielded activation energy, Eα, varying from 36-323 kJ mol-1, respectively. The calorific value of biochars produced in the present study in the range of 265 to 475 ºC was 16,17 to 20,24 MJ kg-1, respectively, which are comparable to those reported values in the literature. Analyzing the DTG simultaneously with the addition of thermal energy, it can be seen that low molecular weight compounds represent the first degradation curves, followed by hemicellulose, cellulose and, lignin. The results obtained in the present work indicate that its feasible to prepare biochars with tunable properties from residual avocado seeds using a slow pyrolysis process, adding commercial value and reducing the environmental impact caused by the inadequate disposal of lignocellulosic materials.

Facile Synthesis of 5-Bromo-N-Alkylthiophene-2-Sulfonamides and Its Activities Against Clinically Isolated New Delhi Metallo-β-Lactamase Producing Klebsiella pneumoniae ST147.

New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae (NDM-1-KP) sequence type (ST) 147 poses a significant threat in clinical settings due to its evolution into two distinct directions: hypervirulence and carbapenem resistance. Hypervirulence results from a range of virulence factors, while carbapenem resistance stems from complex biological mechanisms. The NDM-1-KP ST147 clone has emerged as a recent addition to the family of successful clones within the species. In this study, we successfully synthesized 5-bromo-N-alkylthiophene-2-sulfonamides (3a-c) by reacting 5-bromothiophene-2-sulfonamide (1) with various alkyl bromides (2) using LiH. We also synthesized a series of compounds (4a-g) from compound (3b) using the Suzuki-Miyaura cross-coupling reaction with fair to good yields (56-72%). Further, we screened the synthesized molecules against clinically isolated New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae ST147. Subsequently, we conducted in-silico tests on compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I. The compound (3b) with favourable drug candidate status, MIC of 0.39 μg/mL, and MBC of 0.78 μg/mL. This low molecular weight compound exhibited the highest potency against the resistant bacterial strains. The in-silico tests revealed that the compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I demonstrated H-bond and hydrophobic interactions. The 5-bromo-N-alkylthiophene-2-sulfonamides displayed antibacterial efficacy against New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae ST147. After the in-vivo trial, this substance might offer an alternative therapeutic option.

Solid-phase microextraction - a future technique in pharmacology and coating trends.

Traditional sample preparation techniques based on liquid-liquid extraction (LLE) or solid-phase extraction (SPE) often suffer from a major error due to the matrix effects caused by significant co-extraction of matrix components. The implementation of a modern extraction technique such as solid-phase microextraction (SPME) was aimed at reducing analysis time and the use of organic solvents, as well as eliminating pre-analytical and analytical errors. Solid-phase microextraction (SPME) is an innovative technique for extracting low molecular weight compounds (less than 1500 Da) from highly complex matrices, including biological matrices. It has a wide range of applications in various types of analysis including pharmaceutical, clinical, metabolomics and proteomics. SPME has a number of advantages over other extraction techniques. Among the most important are low environmental impact, the ability to sample and preconcentrate analytes in one step, simple automation, and the ability to extract multiple analytes simultaneously. It is expected to become, in the future, another method for cell cycle research. Numerous available literature sources prove that solid-phase microextraction can be a future technique in many scientific fields, including pharmaceutical sciences. This paper provides a literature review of trends in SPME coatings and pharmacological applications.

One-step electrodeposited hybrid nanofilms in amperometric biosensor development.

This review summarizes recent developments in amperometric biosensors, based on one-step electrodeposited organic-inorganic hybrid layers, used for analysis of low molecular weight compounds. The factors affecting self-assembly of one-step electrodeposited films, methods for verifying their composition, advantages, limitations and approaches affecting the electroanalytical performance of amperometric biosensors based on organic-inorganic hybrid layers were systemized. Moreover, issues related to the formation of one-step organic-inorganic hybrid functional layers with different structures in biosensors produced under the same electrodeposition parameters are discussed. The systemized dependencies can support the preliminary choice of functional sensing layers with architectures tuned for specific biotechnology and life science applications. Finally, the capabilities of one-step electrodeposition of organic-inorganic hybrid functional films beyond amperometric biosensors were highlighted.

Explicating conjugated polymer extraction used for the differentiation of single-walled carbon nanotubes.

Single-walled carbon nanotubes (SWCNTs) are synthesized as mixtures of various SWCNT types, exhibiting drastically different properties, and thereby making the material of limited use. Fluorene-based polymers are successful agents for purifying such blends by means of conjugated polymer extraction (CPE), greatly increasing their application potential. However, a limited number of studies have devoted attention to understanding the effects of the polyfluorene backbone and side chain structure on the selectivity and separation efficiency of SWCNTs. Regarding the impact of the polymer backbone, it was noted that the ability to extract SWCNTs with conjugated polymers could be significantly enhanced by using fluorene-based copolymers that exhibit dramatically different interactions with SWCNTs depending on the types of monomers combined. However, the role of monomer side chains remains much less explored, and the knowledge generated so far is fragmentary. Herein, we present a new approach to tailor polymer selectivity by creating copolymers of polyfluorene bearing mixed-length alkyl chains. Their thorough and systematic analysis by experiments and modeling revealed considerable insight into the impact of the attached functional groups on the capacity of conjugated polymers for the purification of SWCNTs. Interestingly, the obtained results contradict the generally accepted conclusion that polyfluorene-based polymers and copolymers with longer chains always prefer SWCNTs of larger diameters. Besides that, we report that the capacity of such polymers for sorting SWCNTs may be substantially enhanced using specific low molecular weight compounds. The carried-out research provides considerable insight into the behavior of polymers and carbon-based materials at the nanoscale.

Исследование свойств гранулята форполимера полиамида-6

A technological process for low-temperature hydrolytic polymerization of caprolactam in a melt is being developed, which includes two stages: 1) prepolymer synthesis; 2) continuous combined drying–demonomerization of the granulate. The first stage of the process was carried out at a temperature of 210-220°C. The synthesized prepolymer samples were investigated for the content of low molecular weight compounds and relative viscosity.

Ti-based MOF nanosheets as a mass spectrometry imaging matrix for low molecular weight compounds to reveal the spatiotemporal content changes of hepatotoxic components during the processing of Polygonum multiflorum.

The selection of the matrix is crucial for matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). This work successfully synthesized metal-organic framework (MOF) matrices to address the limitations on the application of traditional organic matrices in the study of small molecule compositions, and Ti-based MOF nanosheets were screened as matrices for imaging the hepatotoxic components of Polygonum multiflorum. Comparison between six MOF materials and traditional organic matrices showed that Ti-based MOF nanosheets have less background interference, significant stability, and high salt resistance. The imaging results indicated that the main components of Polygonum multiflorum, free anthraquinone and stilbene glycoside have unique spatial distribution characteristics. Successful application of the synthesized Ti-based MOF nanosheets in mass spectrometry imaging improved the detection ability of mass spectrometry imaging in the small molecule field, and spatiotemporal content changes of hepatotoxic components in Polygonum multiflorum during the steaming process were observed, providing a scientific basis for steaming.

Study of Release of Biologically Active Compounds from Cord Blood Under Different Conditions of Low-Temperature Impact

Here, we have studied the impact of cord blood destruction method on composition of the cord blood-derived low molecular fractions, and compared the cryodestruction with other methods of cell destruction before extracting. Human cord blood was destroyed by rapid or slow freezing / warming, hypotonic lysis and thermal destruction. The obtained substance was used to produce the cord blood fraction (CBF) by multi-stage ultrafiltration and lyophilization. Dry weight, CBF composition and total protein content in them were evaluated by chromatographic profiles (gel permeation and reverse-phase high-performance liquid chromatography). The CBFs, obtained by diff erent techniques for cord blood destruction were established to diff er in the content and molecular weights of the components. These fi ndings suggest the possibility to vary the amount and range of low molecular weight compounds in lyophilized cord blood fractions by using low temperatures and combining diff erent regimens of freezing / warming. Key words: cryodestruction, cord blood, biologically active substances, low-molecular fraction, low temperatures

Fate, behaviour and microbial response of diluted bitumen and conventional crude spills in a simulated warm freshwater environment

Diluted bitumen (DB), one of the most transported unconventional crude oils in Canada's pipelines, raises public concerns due to its potential spillage into freshwater environments. This study aimed to compare the fate and behaviour of DB versus conventional crude (CC) in a simulated warm freshwater environment. An equivalent of 10 L of either DB or CC was spilled into 1200 L of North Saskatchewan River (NSR) water containing natural NSR sediment (2.4 kg) in a mesoscale spill tank and its fate and behaviour at air/water temperatures of 18 °C/24 °C were monitored for 56 days. Oil mass distribution analysis showed that 42.3 wt % of CC and 63.6 wt% of DB resided in the oil slicks at the end of 56-day tests, consisting mainly high molecular weight (HMW) compounds (i.e., resins and asphaltenes). The lost oil contained mainly low molecular weight (LMW) compounds (i.e., light saturates and some aromatics) into the atmosphere, water column, and sediment through collective weathering processes. Notably, weathered CC emulsified with water and remained floating until the end, while the weathered DB mat started to lose its buoyancy after 24 days under quiescent conditions and resurfaced once waves were applied. Analysis of the microbial communities of water pre- and post-spills revealed the replacement of indigenous microbial communities with hydrocarbon-degrading species. Exposure to CC reduced the microbial diversity by 12%, while exposure to DB increased the diversity by 10%. During the early stages of the spill (up to Day 21), most dominant species were positively correlated with the benzene, toluene, ethylbenzene, and xylenes (BTEX) content or polycyclic aromatic hydrocarbon (PAH) content of the water column, while the dominant species at the later stages (Days 21–56) of the spill were negatively correlated with BTEX or PAH content and positively correlated with the total organic carbon (TOC) content in waters.

Determining the sources and distribution of polycyclic aromatic hydrocarbons in the soil of different oil fields at Basrah governorate, Iraq

The object of the research is polycyclic aromatic hydrocarbons (PAHs). For the purpose of determining the source and distribution of PAHs, soil samples from the 11 oil fields in the Basrah governorate (Seba, Safwan, Majnoon, Ratawi, Bergezia, Qurna1, Qurna2, Shuaaba, South and North Rumaila, and al Zubair) were taken at a depth of 0 to 20 cm. According to their molecular weight, they were separated into two main groupings. The first group of compounds consisted of six compounds: naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, and anthracene. These light (low molecular weight) compounds have two to three fused aromatic rings. The first group includes nine chemicals: floranthene, pyrene, benzo(a)anthracene, chrysene, benzo(b), benzo(k), benzo(a), benzo(a), indeno(1,2,3,c,d), and benzo(g,h,i)perylene. These heavy (high molecular weight) compounds included four or more fused aromatic rings. The PAHs compounds ranged in value from the lowest (0.16 ng/g dry weight of benzo(a)anthracene at station West Quarna1) to the highest (680 ng/g dry weight of benzo(g,h,i)perylene that emerged at station North Rumail). The total concentration of PAHs ranged from 77.67 ng/g in South Rumaila Field while highest concentration is 2284.27 ng/g in North Rumail. The PAHs compound has low and high molecular weight, their ratio of LMW/HMW (low molecular weight/high molecular weight) and phenanthrene/anthracene, fluoranthene/pyrene indicated that the source of PAHs was pyrogenic only. The PAH diagnostic ratios and principal component analysis (PCA) indicated that PAHs in soils essentially originated from emissions and combustion. This study gave a baseline on the source and distribution of these compounds in oil fields at Basrah governorate and can be used as a baseline for coming study in the future.

Polycyclic aromatic hydrocarbon (PAH) source identification and a maternal transfer case study in threatened killer whales (Orcinus orca) of British Columbia, Canada

The northeastern Pacific (NEP) Ocean spans the coast of British Columbia (Canada) and is impacted by anthropogenic activities including oil pipeline developments, maritime fossil fuel tanker traffic, industrial chemical effluents, agricultural and urban emissions in tandem with stormwater and wastewater discharges, and forest wildfires. Such events may expose surrounding marine environments to toxic polycyclic aromatic hydrocarbons (PAHs) and impact critical habitats of threatened killer whales (Orcinus orca). We analyzed skeletal muscle and liver samples from stranded Bigg’s killer whales and endangered Southern Resident killer whales (SRKWs) for PAH contamination using LRMS. C3-phenanthrenes/anthracenes (mean: 632 ng/g lw), C4-dibenzothiophenes (mean: 334 ng/g lw), and C4-phenanthrenes/anthracenes (mean: 248 ng/g lw) presented the highest concentrations across all tissue samples. Diagnostic ratios indicated petrogenic-sourced contamination for SRKWs and pyrogenic-sourced burdens for Bigg’s killer whales; differences between ecotypes may be attributed to habitat range, prey selection, and metabolism. A mother-fetus skeletal muscle pair provided evidence of PAH maternal transfer; low molecular weight compounds C3-fluorenes, dibenzothiophene, and naphthalene showed efficient and preferential exposure to the fetus. This indicates in-utero exposure of PAH-contamination to the fetus. Our results show that hydrocarbon-related anthropogenic activities are negatively impacting these top predators; preliminary data found here can be used to improve oil spill and other PAH pollution management and regulation efforts, and inform policy to conserve killer whale habitats in the NEP.

Profile distribution of polycyclic aromatic hydrocarbons in coastal soils of the Lower Don and Taganrog Bay, Russia

The main regularities of pollutant distribution through the soil profile were established based on the analysis of the content of 15 priority PAHs in 29 soil sections of different soil types located in the coastal zone of the Lower Don and Taganrog Bay with different anthropogenic loads. It was shown that the total content of PAHs in the 0-20 cm layer of soils of coastal territories varies from 172 µg kg-1 to 16006 µg kg-1. In addition, according to the total pollution indicator, (Zc) determines the level of soil pollution, which varies from "not polluted" to "extremely polluted". The influence of pollution sources falls on the 0-20 cm layer of soils of different types and is especially pronounced for subordinate landscapes. With increasing sampling depth, the total PAH content decreases with the redistribution of individual compounds of the PAH group towards the dominance of low molecular weight and 4-ring compounds in the composition of the sum of 15 PAHs and depends largely on the content of organic matter and soil pH. Based on the cluster analysis results, the main factor determining the profile distribution of PAHs is the type of pollutant origin source and its intensity.

Harnessing root exudates for plant microbiome engineering and stress resistance in plants

A wide range of abiotic and biotic stresses adversely affect plant's growth and production. Under stress, one of the main responses of plants is the modulation of exudates excreted in the rhizosphere, which consequently leads to alterations in the resident microbiota. Thus, the exudates discharged into the rhizospheric environment play a preponderant role in the association and formation of plant-microbe interactions. In this review, we aimed to provide a synthesis of the latest and most pertinent literature on the diverse biochemical and structural compositions of plant root exudates. Also, this work investigates into their multifaceted role in microbial nutrition and intricate signaling processes within the rhizosphere, which includes quorum-sensing molecules. Specifically, it explores the contributions of low molecular weight compounds, such as carbohydrates, phenolics, organic acids, amino acids, and secondary metabolites, as well as the significance of high molecular weight compounds, including proteins and polysaccharides. It also discusses the state-of-the-art omics strategies that unveil the vital role of root exudates in plant-microbiome interactions, including defense against pathogens like nematodes and fungi. We propose multiple challenges and perspectives, including exploiting plant root exudates for host-mediated microbiome engineering. In this discourse, root exudates and their derived interactions with the rhizospheric microbiota should receive greater attention due to their positive influence on plant health and stress mitigation.

Influence of the black seed oil modified epoxy resin/biscycloaliphatic epoxide monomer weight ratio on thermal properties of photocrosslinked coatings

AbstractThe influence of the black seed oil modified epoxy resin (EBSO)/monomer 3,4‐epoxycyclohexylmethyl 3,4‐epoxycyclohexane carboxylate (BCDE) weight ratio in the coatings based on the compounds and photoinitiator triarylsulfonium hexafluoroantimonate (TAS) on thermal properties of photocrosslinked coatings have been studied. The chemical structure of investigated UV‐cured coatings was characterized by IR spectrometric analysis. Their thermogravimetric (TG) and differential scanning calorimetry (DSC) behavior were determined by TG and DSC analysis, respectively. It was shown that the testing atmosphere had almost no effect to the form of TG, DTG curves and little effect on value of weight degradation of investigated coatings. The volatilization of low molecular weight compounds was observed in the range from room temperature to 360oC while the thermal degradation of the coatings occurred in the range from 360 to 455.5oC. The augmentation of the EBSO/BCDE weight ratio from 20/80 to 80/20 led to an increase of the degradation temperatures in the nitrogen atmosphere; extreme character of weight loss variation as well as the reduction of glass transition temperatures of the coatings from 79.8oC (Tg1) and 83oC (Tg2) to 36.8 (Tg1) and 38.9oC (Tg2), correspondingly.

The Role of Ozonation as an Advanced Oxidation Process for Attenuation of 1,4-Dioxane in Potable Reuse Applications

ABSTRACT The combination of ozone and hydrogen peroxide (O3/H2O2), or the peroxone process, has often been used as an advanced oxidation process (AOP) in groundwater remediation and drinking water applications. This historical precedent sometimes leads to the misconception that H2O2 addition is required to achieve AOP conditions during ozonation. This is not the case for secondary or tertiary wastewater effluent applications, in which ozone reacts with abundant dissolved organic carbon (DOC) to generate hydroxyl radicals (∙OH). This study demonstrates the use of ozone with and without H2O2 addition to yield ∙OH exposures (up to 10−9 M-s) capable of achieving > 0.5-log10 attenuation of the industrial contaminant and probable human carcinogen 1,4-dioxane. This low molecular weight compound is commonly used as a surrogate when establishing AOP design criteria for potable reuse applications. DOC-normalized ozone doses (i.e., O3/DOC ratios) of ~ 1.0 and ~ 1.3 achieved 0.5-log10 attenuation of 1,4-dioxane with O3/H2O2 and O3, respectively. Also, a predictive model based on ∙OH exposure was accurate within approximately ± 10%. These results suggest that ozonation’s role as an AOP, even in the absence of H2O2, should be acknowledged in regulatory frameworks to reduce unnecessary treatment redundancy and facilitate broader implementation of potable reuse.

Dominant heterocyclic composition of dissolved organic nitrogen in the ocean: A new paradigm for cycling and persistence.

Marine dissolved organic nitrogen (DON) is one of the planet's largest reservoirs of fixed N, which persists even in the N-limited oligotrophic surface ocean. The vast majority of the ocean's total DON reservoir is refractory (RDON), primarily composed of low molecular weight (LMW) compounds in the subsurface and deep sea. However, the composition of this major N pool, as well as the reasons for its accumulation and persistence, are not understood. Past characterization of the analytically more tractable, but quantitatively minor, high molecular weight (HMW) DON fraction revealed a functionally simple amide-dominated composition. While extensive work in the past two decades has revealed enormous complexity and structural diversity in LMW dissolved organic carbon, no efforts have specifically targeted LMW nitrogenous molecules. Here, we report the first coupled isotopic and solid-state NMR structural analysis of LMW DON isolated throughout the water column in two ocean basins. Together these results provide a first view into the composition, potential sources, and cycling of this dominant portion of marine DON. Our data indicate that RDON is dominated by 15N-depleted heterocyclic-N structures, entirely distinct from previously characterized HMW material. This fundamentally new view of marine DON composition suggests an important structural control for RDON accumulation and persistence in the ocean. The mechanisms of production, cycling, and removal of these heterocyclic-N-containing compounds now represents a central challenge in our understanding of the ocean's DON reservoir.