L-cysteine Methyl Ester Research Articles

Kinetics and thermodynamics of oxidation mediated reaction in l-cysteine and its methyl and ethyl esters in dimethyl sulfoxide-d6 by NMR spectroscopy

l-Cysteine (L-Cys), l-Cysteine methyl ester (L-CysME) or l-Cysteine ethyl ester (L-CysEE), when dissolved in dimethyl sulfoxide, undergoes an oxidation process. This process is slow enough and leads to nuclear magnetic resonance (NMR) spectral changes that could be monitored in real time. The oxidation mediated transition is modeled as a pseudo-first order kinetics and the thermodynamic parameters are estimated using the Eyring's formulation. l-Cysteine and their esters are often used as biological models due to the remarkable thiol group that can be found in different oxidation states. This oxidation mediated transition is due to the combination of thiol oxidation to a disulfide followed by solvent-induced effects may be relevant in designing cysteine-based molecular models.

Thermally Degradable Polyesters with Tunable Degradation Temperatures via Postpolymerization Modification and Intramolecular Cyclization

We report the novel synthesis of thermally degradable polyesters through the postpolymerization modification of an unsaturated aliphatic polyester from maleic acid via Michael addition reaction with β-amino mercaptans. A high molecular weight polyester (P0) was synthesized by the acyclic diene metathesis (ADMET) polymerization of a diene monomer, di(10-undecenyl) maleate. Postpolymerization modification of P0 with three β-amino mercaptans (2-aminoethanethiol, l-cysteine methyl ester, and 2-(butylamino)ethanethiol) and 2-mercaptoethanol via the selective and quantitative thiol–Michael addition reaction with the maleate vinylic double bonds afforded four polyesters (P1–P4). All the polyesters were characterized by 1H NMR, GPC, and MALDI-TOF-MS, and their thermal properties were studied by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). The three polymers with pendant amino groups (P1–P3) subjected to thermal-induced degradation in the solid state, the driving force of which i...

Efficacy of decontamination foam on a non-polar hazardous chemical surrogate

The release of hazardous chemicals poses a threat to individuals in the area of a release and to responders who attempt to limit the damage of the release. For a liquid phase spill, the most common decontamination technology is a sodium hypochlorite and water solution. Although this solution has been proven effective against a variety of contaminants, it also has a host of drawbacks. Novel decontamination technologies have been developed for military applications, however, they have not been explored with the same depth in the industrial sector. Therefore, there is a need for an industrial decontamination technology that is noncorrosive, nontoxic, nonflammable, and environmentally safe. Decontamination solutions and foams have the potential to improve hazardous chemical spill cleanup, saving time, money, and lives. This work uses a derivative of cysteine, called N-(tert-Butoxycarbonyl)-L-cysteine methyl ester (TCME), as a surrogate for non-polar hazardous industrial bio-chemicals. Previous work has been done to compare the effect of decontamination foam against other decontamination solutions, however in the work the contaminants were typically polar, thus easily able to dissolve in the foam and react rapidly. In this work, the effect of less polar contaminants is studied, introducing transport limitations as well as reaction limitations. Additionally, this work examines the effect of surfactant on decontamination reactions by using water based decontamination solution and decontamination foam as decon technologies. All experiments were conducted in the liquid phase and results were analyzed using GC-MS to determine the extent of reaction.

Vasodilatory effects of nitric oxide, hydrogen sulfide and sulfur dioxide in rats: Time-dependent interaction study

The vasodilator response of nitric oxide (NO), hydrogen sulfide (H2S) and sulfur dioxide (SO2) were studied todetermine the significance of the actions and interactions of these gasotransmitters for controlling aortic tone in rats. The isometric tension of five separate sets of experiments was recorded. Sodium nitroprusside (SNP; NO donor), sodium disulphide (Na2S; H2S donor), SO2 derivatives and their paired combinations were added to phenylephrine (PE)-induced contraction during the peak value. Then maximal relaxation rate was calculated four times at 5 min intervals. Tetraethylammonium (TEA) and Glibenclamide (GLIB) were applied for investigating the molecular mechanism of the gasses. While, in a separate set of experiments, we used either L-Arginine (L-Arg), L-Cysteine (L-Cyst) or L-nitroarginine methyl ester (L-NAME) before applying gasotransmitters. Highest and prolonged relaxation rate were recorded when SNP was combined with SO2. The combination of Na2S and SO2-induced vasorelaxation was blocked by TEA and GLIB pretreatments. L-Cyst decreased relaxation compared to SNP and vice versa to SO2 induced vasorelaxation. L-Arg markedly attenuated relaxation responses of Na2S and SO2 derivatives. Also, L-NAME delayed relaxation compared to Na2S and SO2. These results suggest that exogenous paired combinations of H2S, NO and SO2 will enhance and elongate the rate of aortic relaxation. Meanwhile, preincubation of aortic rings with precursors attenuate the dilatory effects of exogenous studied gases.

Physiologically relevant plasma d,l-homocysteine concentrations mobilize Cd from human serum albumin.

Although low-level chronic exposure of humans to cadmium (Cd(2+)) can result in a variety of adverse health effects, little is known about the role that its interactions with plasma proteins and small molecular weight (SMW) ligands in the bloodstream may play in delivering this metal to its target organs. To gain insight, a Cd-human serum albumin (HSA) 1:1 (molar ratio) complex was analyzed by size exclusion chromatography (SEC) coupled on-line to a flame atomic absorption spectrometer (FAAS). Using a phosphate buffered saline (PBS)-buffer mobile phase, the stability of the Cd-HSA complex was investigated in the presence of 2.0mM of SMW ligands, including taurine, acetaminophen, l-methionine, l-cysteine (Cys), d,l-homocysteine (hCys) or l-cysteine methyl-ester (Cys-Me). While taurine, acetaminophen and l-methionine did not affect its integrity, Cys, hCys and Cys-Me completely abstracted Cd from HSA. Subsequent investigations into the effect of 1.5, 1.0 and 0.5mM Cys and hCys on the integrity of the Cd-HSA complex revealed clear differences with regard to the nature of the eluting SMW-Cd species between these structurally related endogenous thiols. Interestingly, the Cd-specific chromatograms that were obtained for 0.5mM hCys revealed the elution of an apparent mixture of the parent Cd-HSA complex with a significant contribution of a structurally uncharacterized CdxhCysy species. Since this hCys concentration is encountered in blood plasma of hyperhomocysteinemia patients and since previous studies by others have revealed that a SH-containing carrier mediates the uptake of Cd into hepatocytes, our results suggest that plasma hCys may play a role in the toxicologically relevant translocation of Cd from the bloodstream to mammalian target organs.

Hemicucurbiturils as receptors in extraction and transport of some amino acids

The molecular recognition properties of hemicucurbit[6]uril (HemiCB[6]) and hemicucurbit[12]uril (HemiCB[12]) towards a series of amino acid native and methyl esters (L-phenylalanine, L-leucine, L-valine, L-cysteine, L-tryptophan, L-isoleucine, L-phenylalanine methyl ester hydrochloride (L-PheOMe), L-tyrosine methyl ester hydrochloride (L-TyrOMe), L-valine methyl ester hydrochloride (L-ValOMe), L-leucine methyl ester hydrochloride (L-LeuOMe), L-serine methyl ester hydrochloride (L-SerOMe) and L-cysteine methyl ester hydrochloride (L-CysOMe) were investigated. In this respect, by means of liquid–liquid extraction, a series of amino acid native and methyl esters were extracted from an aqueous phase (pH = 5.5) into a chloroform phase as ion pairs in the presence of tropaeolin 00 as counterion. Based on results obtained in extraction experiments, the active transport assisted by pH gradient of amino acids as ion pairs through chloroform liquid membrane employing HemiCB[6] as carrier was performed. Both receptors used in experiments exhibited extractability towards amino acids under study. From the results obtained, one can observed the good affinity of both receptors, hemiCB[6, 12], towards hydrophobic amino acids (L-PheOMe, L-LeuOMe and L-ValOMe)). It was emphasised that the structure of hemicucurbiturils and amino acids together with the anion nature, and pH have influenced the experimental results.

Prevention of cyclophosphamide-induced hepatotoxicity and genotoxicity: Effect of an L-cysteine based oxovanadium(IV) complex on oxidative stress and DNA damage.

Vanadium has been emerged as a promising agent owing to its ability to prevent several types of cancer. This study was aimed to investigate the protective role of an organovanadium complex, viz., oxovanadium(IV)-L-cysteine methyl ester (VC-IV) against cyclophosphamide (CP)-induced hepatotoxicity and genotoxicity in mice. Oral administration of VC-IV quite effectively ameliorated CP-induced histopathological lesions and reduced levels of alanine transaminase, aspartate transaminase and alkaline phosphatase. In addition, VC-IV significantly attenuated CP-induced oxidative stress in the liver as evident from levels of reactive oxygen species, nitric oxide and lipid peroxidation. Restoration of glutathione level and activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase) were also observed upon VC-IV administration. Moreover, VC-IV significantly mitigated CP-induced chromosomal aberrations, micronuclei formation, DNA fragmentation and apoptosis in bone marrow cells and DNA damage in lymphocytes. The present study showed that VC-IV could provide adequate protection against CP-induced hepatotoxicity and genotoxicity in vivo.

Total synthesis of pro-resolving and tissue-regenerative Protectin sulfido-conjugates

The stereospecific total synthesis of the pro-resolving and tissue-regenerative Protectin sulfido-conjugates: 16R,17S-PCTR1, 16R,17S-PCTR2, and 16R,17S-PCTR3, derived from docosahexaenoic acid, has been achieved. The key intermediate 16S,17S-epoxy-Protectin methyl ester was synthesized using the Sharpless catalytic asymmetric epoxidation to generate the chiral centers at C16 and C17. A Cs2CO3 promoted coupling provided the skipped diyne intermediate. Wittig reactions and epoxide opening with glutathione, l-cysteinylglycine, and l-cysteine methyl ester hydrochloride, respectively, were the key steps in the synthesis.

Evaluation of the physicochemical properties and the biocompatibility of polyethylene glycol-conjugated gold nanoparticles: A formulation strategy for siRNA delivery

The potential of RNA interference (RNAi)-based therapeutics for cancer has received much attention; however, delivery of RNAi effectors, such as small interfering RNA (siRNA), remains an obstacle to clinical translation. Non-viral delivery vectors have been used extensively to enhance siRNA delivery. Recently, the potential of gold nanoparticles (AuNPs) for transporting drugs, proteins and genetic materials has been demonstrated. Previously, our laboratory synthesised positively charged, surfactant-free AuNPs in water by the reduction of gold (III) chloride (AuCl3) using hydroxylamine hydrochloride (NH2OH·HCl) in the presence of l-cysteine methyl ester hydrochloride (HSCH2CH(NH2)COOCH3·HCl) as a capping agent. These AuNPs, which achieve higher cell viability in comparison to cetyl trimethyl ammonium bromide (CTAB, a surfactant)-capped counterparts, have demonstrated potential for siRNA delivery. However, it is well known that systemic administration of cationic delivery systems without biological stablising moieties causes non-specific binding with negatively charged serum proteins, resulting in particle aggregation and opsonisation. Consequently, highly stable AuNPs capped with l-cysteine methyl ester hydrochloride conjugated to poly(ethylene glycol) (PEG) were synthesised in this study. PEGylation enhanced the biocompatibility of the AuNPs by reducing toxicity in a range of cell types, by inhibiting interaction with serum proteins thus avoiding aggregation, and, by providing protection against degradation by nucleases. Moreover, these PEGylated AuNPs formed nanoparticles (NPs) with siRNA (which was first compacted with protamine), and had a diameter within the nanoscale range (∼250nm) and a near neutral surface charge (∼10mV). In the future a bifunctional PEG chain on the AuNPs (i.e., SH-PEG-NH2, SH-PEG-COOH) will be used to facilitate conjugation of a targeting ligand to enhance cell specific uptake.

First total synthesis of pro-resolving and tissue-regenerative Maresin sulfido-conjugates

The first stereospecific total synthesis of the pro-resolving and tissue-regenerative Maresin sulfido-conjugates: 13R,14S-MCTR1, 13R,14S-MCTR2 and 13R,14S-MCTR3, derived from docosahexaenoic acid, has been achieved. The key intermediate 13S,14S-epoxy-Maresin methyl ester was synthesized using a chiral pool strategy starting from 2-deoxy-d-ribose. Wittig reactions, selective epoxide formation and epoxide opening with glutathione, l-cysteinylglycine and l-cysteine methyl ester hydrochloride respectively, were the key steps in the synthesis.

Modification of aluminum–silicate nanoparticles by melamine-based dendrimer l-cysteine methyl esters for adsorptive characteristic of Hg(II) ions from the synthetic and Persian Gulf water

l-Cysteine methyl ester-cyanuric-Si/Al (Si/Al@CN@CME) with high adsorption selectivity for Hg(II) ions was synthesized by covalent immobilization of an amino acid on the modified SiO2/Al2O3 mixed oxide nanoparticle. The synthesized nanomaterials were characterized by nuclear magnetic resonance spectrum (1H NMR and 13C NMR), Fourier transform infrared spectroscopy (FT-IR), diffuse reflectance UV–vis spectroscopy (DR UV–vis), inductively coupled plasma atomic emission spectroscopy (ICP-AES), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET) and elemental analysis. Results showed that l-cysteine methyl ester groups were successfully anchored onto the surface of SiO2/Al2O3. Equilibrium and kinetic models for Hg(II) ions sorption was applied by considering the effect of the contact time, initial Hg(II) ions concentrations, effect of temperature, and initial pH. The contact time to attain equilibrium for maximum adsorption was 45min (3079mgg−1). The adsorption of mercury ions has been studied in terms of pseudo-first- and second-order kinetics, and the Freundlich, Langmuir and Langmuir–Freundlich isotherms models have also been used to the equilibrium adsorption data. The adsorption kinetics followed the mechanism of the pseudo-second order equation, confirming chemical sorption as the rate-limiting step of adsorption mechanisms and not involving mass transfer in solution, which was confirmed by techniques of DS UV–vis. The thermodynamic parameters (ΔG, ΔH and ΔS) indicated that the adsorption of Hg(II) ions was feasible, spontaneous and chemically exothermic in nature between 25 and 80°C. The nanoadsorbent showed high reusability due to its high adsorption capacity after 12th adsorption–desorption cycles. The developed adsorbent could also be used to remove the mercury(II) from the real sample (Persian Gulf water).

Novel Cystine Ester Mimics for the Treatment of Cystinuria-induced Urolithiasis in a Knockout Mouse Model

To assess the effectiveness of l-cystine dimethyl ester (CDME), an inhibitor of cystine crystal growth, for the treatment of cystine urolithiasis in an Slc3a1 knockout mouse model of cystinuria. CDME (200 μg per mouse) or water was delivered by gavage daily for 4 weeks. Higher doses by gavage or in the water supply were administered to assess organ toxicity. Urinary amino acids and cystine stones were analyzed to assess drug efficacy using several analytical methods. Treatment with CDME led to a significant decrease in stone size compared with that of the water group (P = .0002), but the number of stones was greater (P = .005). The change in stone size distribution between the 2 groups was evident by micro computed tomography. Overall, cystine excretion in urine was the same between the 2 groups (P = .23), indicating that CDME did not interfere with cystine metabolism. Scanning electron microscopy analysis of cystine stones from the CDME group demonstrated a change in crystal habit, with numerous small crystals. l-cysteine methyl ester was detected by ultra-performance liquid chromatography-mass spectrometer in stones from the CDME group only, indicating that a CDME metabolite was incorporated into the crystal structure. No pathologic changes were observed at the doses tested. These data demonstrate that CDME promotes formation of small stones but does not prevent stone formation, consistent with the hypothesis that CDME inhibits cystine crystal growth. Combined with the lack of observed adverse effects, our findings support the use of CDME as a viable treatment for cystine urolithiasis.

NMR ANALYSIS AND HYDROLYSIS STUDIES OF GLYCYRRHIZIC ACID, A MAJOR CONSTITUENT OF GLYCYRRHIA GLABRA

From the commercial extract of the roots of Glycyrrhia glabra , a triterpene glycoside was isolated which was characterized as 18β-glycyrrhetinic acid-3- O -β- D -glucuronopyranosyl-(1→2)-β- D -glucuronide; also known as Glycyrrhizic acid or Glycyrrhizin. The complete 1 H and 13 C NMR assignments of Glycyrrhizin were achieved by the extensive 1D and 2D NMR ( 1 H and 13 C, COSY, HMQC, and HMBC) as well as mass spectral data. Further, hydrolysis studies were performed on Glycyrrhizin to identify aglycone and sugar residues in its structure. Further, configuration of sugar moieties in the triterpene obtained during the course of acid hydrolysis studies were confirmed by preparing their corresponding thiocarbamoyl-thiazolidine carboxylate derivatives with L-cysteine methyl ester and O -tolyl isothiocyanate and in comparison of their retention times with standard sugars.

A derivatization method for the simultaneous detection of glucosinolates and isothiocyanates in biological samples

Various analytical methods have been established to quantify isothiocyanates (ITCs) that derive from glucosinolate hydrolysis. However, to date there is no valid method applicable to pharmacokinetic studies that detects both glucosinolates and ITCs. A specific derivatization procedure was developed for the determination of ITCs based on the formation of a stable N-(tert-butoxycarbonyl)-l-cysteine methyl ester derivative, which can be measured by high-performance liquid chromatography with ultraviolet detection after extraction with ethylacetate. The novel method, which is also applicable to the indirect determination of glucosinolates after their hydrolysis by myrosinase, was established for the simultaneous determination of glucoraphanin and sulforaphane. By derivatization, the sensitivity of ITC detection was increased 2.5-fold. Analytical recoveries from urine and plasma were greater than 75% and from feces were approximately 50%. The method showed intra- and interday variations of less than 11 and 13%, respectively. Applicability of the method was demonstrated in mice that received various doses of glucoraphanin or that were fed a glucoraphanin-rich diet. Besides glucoraphanin and sulforaphane, glucoerucin and erucin were detected in urine and feces of mice. The novel method provides an essential tool for the analysis of bioactive glucosinolates and their hydrolysis products and, thus, will contribute to the elucidation of their bioavailability.

Synthesis of L-Cysteine grafted nanoporous carbon (CMK-3) and its use as a new cadmium sorbent

Mesoporous silica SBA-15 synthesized by hydrothermal method has been used as template silica and sucrose as the carbon source, in preparation of CMK-3. This was carboxylated by ammonium persulfate ((NH4)2S2O8) and H2SO4, and functionalized with L-Cysteine methyl ester hydrochloride. The resulting samples were characterized by Fourier transform infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM), and Nitrogen adsorption–desorption measurements (BET). The functionalized product shows the BET surface area of 548.4m2g−1 and pore diameter 26.1Å. Cadmium sorption conditions such as the pH value, contact time, adsorbent dose, in batch system have been optimized. Under the experimental conditions, the adsorption capacity for cadmium has been 198mgg−1. The increment in the Cd(II) adsorption capacity of CMK-3 functionalized with L-Cysteine is attributed to the oxygenous and thiols functional groups formed on the surface of CMK-3 which can react with Cd(II).

Study of a cysteine derivative as a corrosion inhibitor for carbon steel in phosphoric acid solution

Inhibition of corrosion of carbon steel in phosphoric acid solution by use of l-cysteine methyl ester hydrochloride has been investigated by measurement of weight loss and use of electrochemical methods. The efficiency of inhibition was increased by increasing the concentration of the inhibitor and reduced by increasing the temperature. Polarization studies revealed that this compound behaves as mixed-type inhibitor. Electrochemical impedance spectroscopy showed that dissolution of the steel occurs as a result of charge-transfer. Adsorption of the inhibitor obeyed the Langmuir adsorption isotherm. Kinetic and thermodynamic data were calculated and are discussed.

Characterization of Cobalt(III) Hydroxamic Acid Complexes Based on a Tris(2-pyridylmethyl)amine Scaffold: Reactivity toward Cysteine Methyl Ester

Six Co(III) complexes based on unsubstituted or substituted TPA ligands (where TPA is tris(2-pyridylmethyl)amine) and acetohydroxamic acid (A), N-methyl-acetohydroxamic acid (B), or N-hydroxy-pyridinone (C) were prepared and characterized by mass spectrometry, elemental analysis, and electrochemistry: [Co(III)(TPA)(A-2H)](Cl) (1a), [Co(III)((4-Cl(2))TPA)(A-2H)](Cl) (2a), [Co(III)((6-Piva)TPA)(A-2H)](Cl) (3a), [Co(III)((4-Piva)TPA)(A-2H)](Cl) (4a) and [Co(III)(TPA)(B-H)](Cl)(2) (1b), and [Co(III)(TPA)(C-H)](Cl)(2) (1c). Complexes 1a-c and 3a were analyzed by (1)H NMR, using 2D ((1)H, (1)H) COSY and 2D ((1)H, (13)C) HMBC and HSQC, and shown to exist as a mixture of two geometric isomers based on whether the hydroxamic oxygen was trans to a pyridine nitrogen or to the tertiary amine nitrogen. Complex 3a exists as a single isomer that was crystallized. Its crystal structure revealed the presence of an H-bond between the pivaloylamide and the hydroximate oxygen. Complexes 1a, 2a, and 4a are irreversibly reduced beyond -900 mV versus SCE, while complexes 1b and 1c are reduced at less negative values of -330 and -190 mV, respectively. The H-bond in 3a increased the redox potential up to -720 mV. Reaction of complex 1a with L-cysteine methyl ester CysOMe was monitored by (1)H NMR and UV-vis at 2 mM and 0.2 mM in an aqueous buffered solution at pH 7.5. Complex 1a was successively converted into an intermediate [Co(III)(TPA)(CysOMe-H)](2+), 1d, by exchange of the hydroximate with the cysteinate ligand, and further into Co(III)(CysOMe-H)(3), 5. An authentic sample of 1d was prepared and thoroughly characterized. A detailed (1)H NMR analysis showed there was only one isomer, in which the thiolate was trans to the tertiary amine nitrogen.

Stereoselective synthesis of highly functionalized thiopeptide thiazole fragments from uronic acid/cysteine condensation products: access to the core dipeptide of the thiazomycins and nocathiacins

We present the stereoselective synthesis of various highly functionalized thiazole dipeptides that are found in thiopeptide antibiotics like thiazomycins and nocathiacins. The condensation of an uronic acid with l-cysteine methyl ester delivers along two different protocols the stereopure thiazolidine lactones or lactams on the multigram scale, respectively. Oxidation of the thiazolidine moiety to the thiazole and tailoring of the sugar chains yield the thiazole dipeptide as present in the core motif of the thiopeptide antibiotics, as well as its epimer and a homolog. The modular assembly of the potent natural products and their analogs relies on the synthetic accessibility of adequately protected building blocks of tailored absolute stereochemistry.

Simultaneous Determination of the Absolute Configuration of Twelve Monosaccharide Enantiomers from Natural Products in a Single Injection by a UPLC-UV/MS Method

In natural product chemistry, it is often crucial to determine sugar composition as well as the absolute configuration of each monosaccharide in glycosides. An ultra-performance liquid chromatography method using both photodiode array (PDA) and mass spectrometry detectors (UPLC-UV/MS) was developed for qualitative analysis of the absolute configuration of monosaccharide enantiomers. Within a single injection, 16 monosaccharide derivatives including 6 pairs of aldose enantiomers (D/L-glucose, D/L-galactose, D/L-allose, D/L-arabinose, D/L-xylose, and D/L-fucose) and 4 other monosaccharides (L-rhamnose, 2-deoxy-D-glucose, 6-deoxy-D-glucose, and 2-deoxy-D-glalactose) were identified in less than 25 minutes. It was found that the structures of derivatives of sugar enantiomers correlated with retention time. Among derivatives of sugar enantiomers in the current study, the stereoisomer of R-configuration at C-3' retained longer than the corresponding S-configuration isomer. The UPLC-MS method can increase sensitivity of detection of the saccharides by more than 10 times compared to previously reported methods. The one-pot reaction of monosaccharide with L-cysteine methyl ester and phenyl isothiocyanate is easily reproduced, clean, and relatively simple in a screw-capped reaction vial. The developed method was successfully applied for the analysis of different types of glycosides, viz., glycosides of triterpenes, steroids, and flavonoids, that commonly exist in nature. The absolute configurations of composed monosaccharides are clearly characterized from tested samples.

Surface-Enhanced Raman Scattering Spectroscopy of Explosive 2,4-Dinitroanisole using Modified Silver Nanoparticles

2,4-Dinitroanisole (DNAN) is being used as a replacement for 2,4,6-trinitrotoluene (TNT) as a less-sensitive melt-cast medium explosive than TNT. In this paper, we studied the surface-enhanced Raman spectroscopy (SERS) analysis of DNAN using Ag nanoparticles (AgNPs) modified by L-cysteine methyl ester hydrochloride. Due to the formation of a Meisenheimer complex between DNAN and the modifier, the modified AgNPs can detect 20 μg/L (0.2 ng) and 0.1 mg/L (1 ng) DNAN in deionized water and aged tap water, respectively. Three other chemicals (L-cysteine, N-acetyl-L-cysteine, and L-cysteine ethyl ester hydrochloride) were used as AgNPs modifiers to study the mechanism of the SERS of DNAN. It was confirmed that the amino group of L-cysteine methyl ester hydrochloride was the active group and that the methyl ester group significantly contributed to the high SERS sensitivity of DNAN. In order to further test the mechanism of Meisenheimer complex formation, the effect of anions and cations present in natural water on the SERS of DNAN was studied. It was found that CO(3)(2-), Cl(-), and K(+) at 100 mg/L did not negatively affect the SERS of 10 mg/L DNAN, while SO(4)(2-), Na(+), Mg(2+), and Ca(2+) at 100 mg/L significantly quenched the SERS of 10 mg/L DNAN. The negative effect of the bivalent cations could be offset by SO(4)(2-).