Molecular Identity and Classification

5-Amino-1MQ is the common research name for 5-amino-1-methylquinolinium, systematically 1-methylquinolin-1-ium-5-amine. Despite being sold alongside research peptides, it is not a peptide at all: it is a small aromatic organic cation built on the quinoline ring system, with a methyl group on the ring nitrogen and a primary amino group at carbon 5. Because the ring nitrogen carries four bonds, the molecule is permanently positively charged and always exists as a salt with a counterion.

The cation has the formula C₁₀H₁₁N₂⁺, a molecular weight of 159.21 g/mol and an exact mass of 159.0922 Da (PubChem CID 950107, CAS 685079-15-6). The material is supplied as the iodide salt, C₁₀H₁₁IN₂, with a molecular weight of 286.11 g/mol (PubChem CID 66522933, CAS 42464-96-0). The distinction matters in practice: the iodide accounts for about 44% of the salt's mass, so 1 mg of the salt contains about 0.56 mg of the active cation, and molar concentrations must be calculated with the salt's molecular weight.

The compound belongs to a family of N-methylated quinolinium and pyridinium compounds studied as inhibitors of nicotinamide N-methyltransferase (NNMT). NNMT transfers a methyl group from S-adenosyl-L-methionine (SAM) to the ring nitrogen of nicotinamide, producing 1-methylnicotinamide and S-adenosyl-L-homocysteine. 5-Amino-1MQ resembles the product of that reaction: like 1-methylnicotinamide, it is an aromatic ring carrying an N-methyl quaternary nitrogen. That structural mimicry is the starting point of its use as a research tool.

Structure and Chemical Features

Quinoline is a fused bicyclic heteroaromatic system: a benzene ring fused to a pyridine ring. In 5-Amino-1MQ the nitrogen of the pyridine ring (position 1) is methylated, which converts the neutral, weakly basic quinoline into a quinolinium cation. The positive charge is delocalized over the heterocyclic ring, which makes the ring electron-poor and strongly polar. The amino group sits on the carbocyclic ring at position 5, peri to the ring junction and across the molecule from the charged nitrogen.

The amino group behaves like an aromatic amine (an aniline-type nitrogen), but its basicity is much lower than that of aniline because the adjacent cationic ring pulls electron density away from it. Its lone pair is partly conjugated into the electron-poor ring system, giving the molecule a donor–acceptor (push–pull) character. This electronic structure explains the compound's colour: the push–pull chromophore absorbs visible light at the blue end of the spectrum, so the solid and its solutions appear yellow to orange.

The planar, rigid ring system has no rotatable bonds apart from the methyl and amino groups. PubChem lists a topological polar surface area of 29.9 Ų, one hydrogen-bond donor (the amine) and a calculated XLogP of 1.1 for the cation; the permanent charge, however, dominates the molecule's behaviour in water and towards membranes far more than the partition coefficient of the neutral framework would suggest.

The Iodide Counterion

Iodide is the natural counterion for this compound because the classic synthesis uses methyl iodide (see Synthesis). It is a large, polarizable, weakly hydrated anion that forms well-crystallizing salts with aromatic cations. It also has a chemical liability: iodide is slowly oxidized by air and light to iodine and triiodide, which are themselves coloured. A gradual deepening of colour over time, particularly in solution exposed to light, is a sign of iodide oxidation and not necessarily of change to the quinolinium cation.

Synthesis and Manufacturing Chemistry

N-Alkylquinolinium salts are prepared by the Menshutkin reaction: the nucleophilic ring nitrogen of a quinoline attacks an alkyl halide, forming a new carbon–nitrogen bond and a quaternary ammonium halide in a single step. For 5-Amino-1MQ the starting material is 5-aminoquinoline and the alkylating agent is methyl iodide; heating the two in a polar aprotic solvent such as acetonitrile or acetone gives 5-amino-1-methylquinolinium iodide, which typically precipitates from the reaction mixture. Neelakantan and colleagues used this kind of chemistry to prepare the quinolinium analogues in their structure–activity study.

The selectivity of the reaction depends on the different nucleophilicity of the two nitrogens. The ring nitrogen of quinoline is the stronger nucleophile; the 5-amino group, being an aromatic amine, is less nucleophilic, so methylation occurs preferentially on the ring. Over-alkylation of the amino group is the main side reaction to control, and it is minimized by limiting the excess of methyl iodide and the reaction temperature.

Purification usually exploits the salt's solubility: the product is washed free of unreacted starting material with a solvent in which the neutral 5-aminoquinoline dissolves but the ionic product does not, and is then recrystallized or purified by reversed-phase chromatography. If a different counterion is wanted (chloride, for example), ion exchange replaces the iodide. The isolated salt is dried to a free-flowing powder, either under vacuum or by freeze-drying an aqueous solution of the purified material.

Analytical Characterization

Mass spectrometry. Because the molecule is already a cation, electrospray ionization in positive mode shows it directly as M⁺ at m/z 159.092, with no need for protonation. Strictly, the ion's m/z is 159.0917: the monoisotopic mass of 159.0922 Da quoted by PubChem is computed on a neutral-atom basis, and the single missing electron (0.00055 Da) accounts for the difference, which matters at the 5 ppm windows typical of high-resolution instruments. From the natural abundances of ¹³C and ¹⁵N, the M+1 isotope peak is expected at about 11.7% of the monoisotopic peak and M+2 at about 0.6%, a useful quick confirmation that the elemental composition is C₁₀H₁₁N₂. The iodide does not appear in positive mode; in negative mode it is observed at m/z 126.9045 as a single isotope, iodine being monoisotopic, which makes the counterion unusually easy to confirm. Tandem MS of the cation typically shows loss of the N-methyl group and fragmentation of the heterocyclic ring. Related species a researcher may need to resolve in the same run are nicotinamide (m/z 123.0553 for the protonated molecule) and 1-methylnicotinamide (m/z 137.0709, already a cation), the substrate and product of the enzyme reaction, and the cofactor pair SAM (m/z 399.1445) and SAH (m/z 385.1289 protonated).

Liquid chromatography. Permanently charged, polar cations retain poorly on conventional C18 reversed-phase columns with simple water–acetonitrile gradients. Analysts therefore use ion-pairing reagents (such as heptafluorobutyric acid or alkyl sulfonates) to increase retention, polar-embedded reversed-phase columns, or hydrophilic interaction chromatography (HILIC), the technique Alpert described in 1990 for separating polar compounds. Detection by UV is straightforward because the aminoquinolinium chromophore absorbs strongly in the ultraviolet and visible regions.

Nuclear magnetic resonance. ¹H NMR in deuterated solvent shows the characteristic N-methyl singlet shifted downfield by the adjacent positive charge (typically near 4.5 ppm), six aromatic protons in the 7–9.5 ppm region, with the proton at position 2 (adjacent to the charged nitrogen) the most downfield, and the exchangeable amine protons. These signals confirm both the position of methylation and the integrity of the amino group.

Counterion and composition. Ion chromatography or argentometric titration quantifies the iodide; elemental analysis (C, H, N, I) confirms the salt stoichiometry. Purity of the organic cation is reported from the chromatographic method, and each lot's certificate of analysis on this page records the results for that material.

Physicochemical Properties

The salt dissolves in water and in polar organic solvents such as dimethyl sulfoxide and methanol, and is poorly soluble in non-polar solvents. In solution the cation is chemically robust: the quinolinium ring does not hydrolyse under ordinary laboratory conditions, and the N-methyl bond is stable. The main practical sensitivities are to light, which promotes oxidation of the iodide counterion, and to strongly basic conditions, under which electron-poor N-alkylquinolinium rings can add hydroxide at the carbon adjacent to the nitrogen.

A worked example of the salt correction: to prepare 1 mL of a 10 mM solution of the cation, weigh 2.86 mg of the iodide salt (10 mmol/L × 0.001 L × 286.11 g/mol), not 1.59 mg. Using the cation's molecular weight with the salt would give a solution at only about 56% of the intended concentration.

These figures are arithmetic from the salt's formula weight and assume the weighed solid is the anhydrous mono-iodide; a lot's recorded purity, shown live on this page, scales them proportionally.

Research Context

NNMT is a cytosolic methyltransferase first cloned and characterized biochemically by Aksoy and colleagues in 1994. Its crystal structure, solved by Peng and colleagues in 2011, shows a compact Rossmann-fold methyltransferase in which SAM binds in a conserved pocket and nicotinamide binds in an adjacent, more variable pocket lined by aromatic and hydrophobic residues. The reaction is a direct S_N2 transfer of the methyl group from the sulfonium of SAM to the pyridine nitrogen of nicotinamide. Pissios reviewed the enzyme's biochemistry and its connections to cellular methyl-group and NAD⁺ metabolism in 2017. The reaction sits at the junction of two cofactor pools: its methyl donor is SAM, the cell's principal methylating agent, and its substrate, nicotinamide, is the salvage-pathway precursor of NAD⁺. Methylation is a committed step, because 1-methylnicotinamide cannot re-enter the salvage pathway; in vitro systems therefore use NNMT activity as a readout for flux out of the nicotinamide pool, and an inhibitor such as 5-Amino-1MQ as the tool for perturbing that flux in enzyme and cell-extract experiments.

Neelakantan and colleagues reported in 2017 a structure–activity study of small-molecule NNMT inhibitors built around the N-methylated aromatic scaffold of the enzyme's product. Screening a series of quinolinium, isoquinolinium, pyridinium and benzimidazolium analogues in an enzyme assay, they reported a span of more than 1000-fold in activity across the series and identified the quinolinium scaffold as the most promising, with the best quinoliniums inhibiting at very low micromolar concentrations (reported IC₅₀ values near 1 µM). Docking of the inhibitors into the nicotinamide-binding site correlated with the measured potencies and placed the quinolinium ring in the substrate pocket. Because 5-Amino-1MQ belongs to that scaffold and mimics the reaction product, it is used as a reference inhibitor in biochemical studies of the enzyme.

How NNMT Activity Is Measured

Enzyme assays follow either the methylated product or the demethylated cofactor. Van Haren and colleagues described in 2016 a rapid assay that separates the reaction products by ultra-high-performance hydrophilic-interaction chromatography and detects them by quadrupole time-of-flight mass spectrometry, a format suited to characterizing both substrates and inhibitors at high throughput. Other formats couple the production of S-adenosyl-L-homocysteine to a luminescent or fluorescent detection system. Loring and Thompson determined the enzyme's kinetic mechanism in 2018 and reported a rapid-equilibrium ordered pathway in which SAM binds first, nicotinamide second, and the two products are released consecutively; that order matters when an inhibitor is characterized, because a compound competing at the nicotinamide site should be tested at defined, saturating SAM. In such assays 5-Amino-1MQ is used to generate concentration–inhibition curves, to compare new compounds against a known quinolinium inhibitor, and, in competition experiments with nicotinamide, to confirm that a new compound binds the substrate site.

Inhibitor design has since moved in several directions. Babault and colleagues reported in 2018 bisubstrate inhibitors that link a nicotinamide-like fragment to a SAM-like fragment, occupying both pockets at once and reaching much higher potency. Policarpo and colleagues refined the idea in 2019 with an alkyne-linked nicotinamide–SAM conjugate whose rigid linker mimics the linear, 180° geometry of the methyl-transfer transition state, giving sub-nanomolar affinity and an X-ray co-crystal structure that shows the linker spanning the enzyme's methyl-transfer tunnel. Gao and colleagues showed in the same year that adding a naphthalene group to a bisubstrate scaffold, intended to engage the hydrophobic nicotinamide pocket by π–π stacking, raises activity to an IC₅₀ of 1.41 µM in their assay. Comparing inhibitors of these three kinds, a single-site product mimic such as 5-Amino-1MQ, a flexible bisubstrate conjugate and a transition-state-geometry conjugate, is a direct way to study how much each pocket and the tunnel between them contributes to binding.

In cell-based work, the compound's permanent positive charge is the key consideration: it does not cross membranes by passive diffusion the way a neutral molecule would, so its uptake depends on the cell type and on membrane transport of organic cations. Researchers measuring intracellular NNMT activity therefore pair the inhibitor with direct measurement of 1-methylnicotinamide in cell extracts by LC-MS, to confirm target engagement rather than assume it.

Laboratory Handling and Storage

Storage of the solid. Store tightly closed at −20 °C, protected from light and moisture. The iodide counterion is light-sensitive; amber vials or foil wrapping slow the gradual darkening that comes from iodide oxidation. Allow the container to reach room temperature before opening so that moisture does not condense on the solid.

Preparing solutions. The salt dissolves in water and in dimethyl sulfoxide. For assays, a concentrated stock in water or dimethyl sulfoxide (for example 10–50 mM, calculated with the salt's molecular weight of 286.11 g/mol) is diluted into the assay buffer. Keep stock solutions protected from light, divide them into single-use aliquots, and store them frozen. Solutions at neutral or mildly acidic pH are preferred; avoid strongly basic buffers.

Assay controls. Because iodide is a chemically active anion (it can react with oxidants and some detection reagents), an equimolar sodium or potassium iodide control helps distinguish effects of the counterion from effects of the quinolinium cation in sensitive biochemical assays.

Verification. A quick LC-MS check for the M⁺ ion at m/z 159.09 confirms identity, and UV–visible spectroscopy gives a fast check of concentration and colour change over time. The lot's certificate of analysis on this page records the analytical results for the material as supplied.

Frequently Asked Research Questions

What is 5-Amino-1MQ?

5-Amino-1MQ is 5-amino-1-methylquinolinium, a small aromatic organic cation (C₁₀H₁₁N₂⁺, 159.21 g/mol) supplied as its iodide salt (C₁₀H₁₁IN₂, 286.11 g/mol). It is a small molecule, not a peptide.

What is the CAS number of 5-Amino-1MQ?

The iodide salt is CAS 42464-96-0 (PubChem CID 66522933). The cation alone is CAS 685079-15-6 (PubChem CID 950107).

Why is it supplied as an iodide?

The ring nitrogen is methylated with methyl iodide, so the product forms directly as the iodide salt. The cation is permanently charged and always needs a counterion.

How do I calculate molar concentrations?

Use the salt's molecular weight, 286.11 g/mol. The cation is about 55.6% of the salt's mass, so 2.86 mg of the salt in 1 mL gives a 10 mM solution of the cation.

What enzyme does 5-Amino-1MQ inhibit?

Nicotinamide N-methyltransferase (NNMT), which methylates nicotinamide using S-adenosyl-L-methionine. 5-Amino-1MQ resembles the reaction's product, 1-methylnicotinamide, and binds the substrate pocket.

What mass should I see by mass spectrometry?

In positive electrospray the cation appears directly at m/z 159.092. In negative mode the iodide counterion appears at m/z 126.904.

Why does it retain poorly on a C18 column?

It is a small, permanently charged cation. Ion-pairing reagents, polar-embedded reversed-phase columns or hydrophilic interaction chromatography (HILIC) give better retention.

Why is the solid coloured?

The amino group donates electron density into the electron-poor quinolinium ring, a push–pull chromophore that absorbs blue light, so the compound appears yellow to orange. Iodide oxidation on long exposure to light can deepen the colour.

How is NNMT activity measured in vitro?

By quantifying the product 1-methylnicotinamide (by fluorescence or LC-MS) or the by-product S-adenosyl-L-homocysteine (by coupled luminescent or fluorescent assays). 5-Amino-1MQ is used as a reference inhibitor in these assays.

Does 5-Amino-1MQ enter cells by diffusion?

No. Its permanent positive charge prevents passive diffusion across membranes; uptake depends on organic-cation transport, so cell-based studies confirm target engagement by measuring intracellular 1-methylnicotinamide.

How should it be stored?

At −20 °C, tightly closed and protected from light and moisture, because the iodide counterion is light-sensitive.

Where can I see the purity of the lot I am buying?

This page shows the lot number, recorded purity and verified quantity of the lot currently on sale, taken live from the shop's lot-tracking database, with that lot's certificate of analysis.

Sources & Further Reading

1. National Center for Biotechnology Information. PubChem Compound Summary for CID 950107, 1-methylquinolin-1-ium-5-amine. PubChem CID 950107.
2. National Center for Biotechnology Information. PubChem Compound Summary for CID 66522933, 1-methylquinolin-1-ium-5-amine iodide. PubChem CID 66522933.
3. Neelakantan H, Wang HY, Vance V, Hommel JD, McHardy SF, Watowich SJ. Structure–activity relationship for small molecule inhibitors of nicotinamide N-methyltransferase. Journal of Medicinal Chemistry 2017;60(12):5015–5028. doi:10.1021/acs.jmedchem.7b00389
4. Aksoy S, Szumlanski CL, Weinshilboum RM. Human liver nicotinamide N-methyltransferase. cDNA cloning, expression, and biochemical characterization. Journal of Biological Chemistry 1994;269(20):14835–14840. doi:10.1016/S0021-9258(17)36700-5
5. Peng Y, Sartini D, Pozzi V, Wilk D, Emanuelli M, Yee VC. Structural basis of substrate recognition in human nicotinamide N-methyltransferase. Biochemistry 2011;50(36):7800–7808. doi:10.1021/bi2007614
6. Pissios P. Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme. Trends in Endocrinology & Metabolism 2017;28(5):340–353. doi:10.1016/j.tem.2017.02.004
7. van Haren MJ, Sastre Toraño J, Sartini D, Emanuelli M, Parsons RB, Martin NI. A rapid and efficient assay for the characterization of substrates and inhibitors of nicotinamide N-methyltransferase. Biochemistry 2016;55(37):5307–5315. doi:10.1021/acs.biochem.6b00733
8. Babault N, Allali-Hassani A, Li F, et al. Discovery of bisubstrate inhibitors of nicotinamide N-methyltransferase (NNMT). Journal of Medicinal Chemistry 2018;61(4):1541–1551. doi:10.1021/acs.jmedchem.7b01422
9. Loring HS, Thompson PR. Kinetic mechanism of nicotinamide N-methyltransferase. Biochemistry 2018;57(38):5524–5532. doi:10.1021/acs.biochem.8b00775
10. Policarpo RL, Decultot L, May E, Kuzmič P, Carlson S, Huang D, et al. High-affinity alkynyl bisubstrate inhibitors of nicotinamide N-methyltransferase (NNMT). Journal of Medicinal Chemistry 2019;62(21):9837–9873. doi:10.1021/acs.jmedchem.9b01238
11. Gao Y, van Haren MJ, Moret EE, Rood JJM, Sartini D, Salvucci A, et al. Bisubstrate inhibitors of nicotinamide N-methyltransferase (NNMT) with enhanced activity. Journal of Medicinal Chemistry 2019;62(14):6597–6614. doi:10.1021/acs.jmedchem.9b00413
12. Alpert AJ. Hydrophilic-interaction chromatography for the separation of peptides, nucleic acids and other polar compounds. Journal of Chromatography A 1990;499:177–196. doi:10.1016/S0021-9673(00)96972-3

Last reviewed: October 22, 2026