WO2025091123A1 - Mesoionic carbenes - Google Patents

Abstract

The present application provides stable, mesoionic carbene-functionalized self-assembled monolayers on substrate surfaces, and methods and uses thereof. These monolayers bond to metallic surfaces and are more stable than thiol- functionalized coatings. Uses of such mesoionic carbene-functionalized coatings include primers for protecting metal surfaces, protection of metals in microelectronic devices, drug delivery or sensing applications.

Description

MESOIONIC CARBENES

RELATED APPLICATION

This application claims the benefit of the filing date of United States Application No. 63/547,093, filed on November 2, 2023, the contents of which are incorporated herein by reference in their entirety.

FIELD

The present application pertains to the field of materials science. More particularly, the present application relates to carbene-functionalized self-assembled monolayers.

BACKGROUND

Carbon-based ligands known as /V-heterocyclic carbenes (NHCs) have played a role in the field of transition metal complexes [W.A. Herrmann, Angew. Chem. Int. Ed. 41 , 1290 (2002); E. Peris, et al. Coord. Chem. Rev. 248, 2239 (2004)]. These ligands are part of catalysts such as the Grubbs second generation metathesis catalyst [R. M. Thomas, et al. Organometallics 30, 6713 (2011)], and NHC-based cross-coupling catalysts [E. A. B Kantchev, et al. Angew. Chem. Int. Ed. 46, 2768 (2007)]. Unlike most carbenes, which are reactive with limited stability, NHCs typically have one or two heteroatoms adjacent to a carbene carbon (A. Igau, et al. J. Am. Chem. Soc. 110, 6463 (1988); A. J. Arduengo, et al. J. Am. Chem. Soc. 113, 361 (1991 )). These heteroatoms increase NHCs’ stability such that they can usually be prepared on a gram scale (M. Niehues, et al. Organometallics 21 , 2905 (2002)), crystallized (A. J. Arduengo, R. L. Harlow, M. Kline, J. Am. Chem. Soc. 113, 361 (1991)), distilled (M. Niehues, et al. Organometallics 21, 2905 (2002)), and stored for longer periods of time (e.g., 4 years, when stored under N2 in a freezer). An Au-NHC bond is estimated to be on an order of 90 kJ/mol stronger than a corresponding Au- phosphine bond, and twice as strong as metal sulfide bonds in molecular complexes (P. Pyykkd, et al. Chem. Asian J. 1 , 623 (2006)). As such, NHCs have potential to be valuable ligands for protecting and functionalizing gold and other metal surfaces.

The above information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.

SUMMARY

In one aspect, the invention provides a mesoionic carbene precursor of Formula (1), or a hydrated form thereof

where X is a counterion, backbone is H, a substituted or unsubstituted linear, branched or cyclic aliphatic moiety, a substituted or unsubstituted aromatic moiety, a heteroatom, an ether, an amine, an amide, or any combination thereof; and wingtip is a substituted or unsubstituted linear, branched or cyclic aliphatic moiety, a substituted or unsubstituted aromatic moiety, or any combination thereof, wherein a substituent comprises alkyl, alkenyl, alkynyl, aryl, aryl-halide, heteroaryl, cycloalkyl (non-aromatic ring), Si(alkyl)3, Si(alkoxy)3, halo, alkoxyl, amino, alkylamino, alkenylamino, amide, amidine, hydroxyl, thioether, alkylcarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carbonate, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphate ester, phosphonato, phosphinato, cyano, acylamino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, dith iocarboxyl ate, sulfate, sulfato, sulfonate, sulfamoyl, sulfonamide, nitro, nitrile, azido, heterocyclyl, ether, ester, silicon-containing moieties, thioester, transition metal, or a combination thereof.

In one embodiment, X is both a counterion and a base. In one embodiment, Rwingtip is iso-propyl or benzyl. In one embodiment, Rbackbone is H, O-(Ci-Ce-aliphatic), OCH3, CF3, or alkylferrocene. In one embodiment, X is hydrogen carbonate, bicarbonate, carbonate, alkylcarboxylate, arylcarboxylate, carboxylate, halide, triflate, pseudohalide, cyanide, or azide, where alkyl is an aliphatic moiety and aryl is aromatic.

In one embodiment, the compound of Formula (1 ) is:

1 .3-di isopropyl- 1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (MIC^iPr»HI);

1.3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium bromide (MIC^iPr»HBr);

1.3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium chloride MIC^iPr»HCI);

1.3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (MIC^iPr»H2CO3);

1 .3-diisopropyl-6-methoxy-1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (^OMeMIC^iPr»HI);

1 ,3-diisopropyl-6-methoxy-1 /7-imidazo[1 ,2-a]pyridin-4-ium bromide (^OMeMIC^iPr»HBr);

1 ,3-diisopropyl-6-methoxy-1 /7-imidazo[1 ,2-a]pyridin-4-ium chloride (^OMeMIC^iPr»HCI);

1 .3-diisopropyl-6-methoxy-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (^OMeMIC^iPr« H2CO3);

1 .3-diisopropyl-6-(trifluoromethyl)-1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (^CF3MIC^iPr,HI);

1 ,3-diisopropyl-6-(trifluoromethyl)-1 /7-imidazo[1 ,2-a]pyridin-4-ium bromide (^CF3MIC^iPr,HBr);

1 ,3-diisopropyl-6-(trifluoromethyl)-1 /7-imidazo[1 ,2-a]pyridin-4-ium chloride (^CF3MIC^iPr*HCI);

1 .3-diisopropyl-6-(trifluoromethyl)-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (^CF3MIC^iPr»H2CO3);

1.3-dibenzyl-1 H-imidazo[1 ,2-a]pyridin-4-ium iodide (M

1 .3-dibenzyl-1 H-imidazo[1 ,2-a]pyridin-4-ium bromide

1 .3-dibenzyl-1 H-imidazo[1 ,2-a]pyridin-4-ium chloride

1.3-dibenzyl-1 H-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (MIC^Bz»H2CO3); 6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (^OHexMIC^iPr»HI);

6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium bromide

(OHex_M|C^iPr»HBr);

6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium chloride (^OHexMIC^iPr»HCI); 6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (OHe^xM|C^iPr»H2CO₃);

6-((6-Ferrocenohexyl)oxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridin-1 -ium iodide (°^HexFcMIC^iPr«HI);

6-((6-Ferrocenohexyl)oxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridin-1 -ium bromide (°^HexFcMIC^iPr«HBr);

6-((6-Ferrocenohexyl)oxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridin-1 -ium chloride (OHexFc_M|C^iPr»HCI);

6-((6-Ferrocenohexyl)oxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridin-1 -ium hydrogen carbonate (^OHexFcMIC^iPr»H2CO3);

1 ,3-diisopropyl-6-(prop-2-yn-1 -yloxy)-1 /7-imidazo[1 ,2-a]pyridin-4-ium bromide (OPropargyl_M |QiPr.|_| _Br)_;

1 ,3-diisopropyl-6-(prop-2-yn-1 -yloxy)-1 /7-imidazo[1 ,2-a]pyridin-4-ium chloride (OPropargylMICiPr-HCI);

1 ,3-diisopropyl-6-(prop-2-yn-1 -yloxy)-1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (OProp^argyiMICiPr»HI); or

1 ,3-diisopropyl-6-(prop-2-yn-1 -yloxy)-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (^OPr°P^ar9y^|MIC^iPr«H2CO3).

In one aspect, the invention provides a method for forming a self-assembled monolayer that comprises a mesoionic carbene of Formula (2) on a surface of a substrate,

(2), wherein Rbackbone and Rwingti_Pare defined above.

In one embodiment, the surface of the substrate is at least partially chemisorbed to the mesoionic carbene. In one embodiment, the surface comprises carbon (in all of its forms), mica, alumina, silica, titania, silicon, glass, indium tin oxide, Fe, Rh, Ru, Ir, Ni, Pd, Pt, Cu, Cr, Ag, Au, W, Mo, Co, an alloy, steel, brass, bronze, tungsten carbide, calcium carbide, or any combination thereof. In one embodiment, depositing the self-assembled monoloayer provides: surface functionalization; protecting a surface of the substrate; protecting a metal surface; activating a surface for chemical derivatization; activating a metal surface for chemical derivatization; activating a metal surface for catalysis; changing a surface property (e.g., wettability, light transmission, refraction, and/or reflection) of a surface.

In one aspect, the invention provides use of the mesoionic carbene, for detecting, sensing, molecular electronics, biosensors, surface patterning, priming metal surfaces, protecting metal surfaces, protecting metals in microelectronic devices, drug delivery, or sensing applications.

In one embodiment, the mesoionic carbene precursor is a carbenic salt that comprises an anion selected from the group consisting of hydrogen carbonate, bicarbonate, carbonate, carboxylate, alkylcarboxylate, arylcarboxylate, carboxylate, halide, triflate, pseudohalide, cyanide, and azide, where alkyl is an aliphatic moiety and aryl is aromatic, wherein the carbenic salt is optionally in a hydrated form.

In one aspect, the invention provides a mesoionic carbene of Formula (2).

In one embodiment, the compound of Formula (2) is the compound of Formula (1 ) without X. In one embodiment, the compound of Formula (2) is:

1 .3-diisopropylimidazo[1 ,2-a]pyridine (MIC^iPr

1 .3-diisopropyl-6-methoxyimidazo[1 ,2-a]pyridine (^OMeMIC^iPr);

1 .3-diisopropyl-6-trifluoromethylimidazo[1 ,2-a]pyridine (^CF3MIC^iPr);

1 .3-dibenzylimidazo[1 ,2-a]pyridine (MIC^Bz);

6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridine (^OHexMIC

6-((6-Ferrocenohexyl)oxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridine

1.3-diisopropyl-6-(prop-2-yn-1-yloxy)-1 /7-imidazo[1 ,2-a]pyridine

BRIEF DESCRIPTION OF THE DRAWINGS

For a better understanding of the invention and to show more clearly how it may be carried into effect, reference will now be made, by way of example, to the accompanying drawings, wherein:

Fig. 1A shows structural formula for NHC^iPr on gold and MIC^iPr on gold and lists characteristics of the MIC^iPr self-assembled monolayers on gold surfaces.

Fig. 1 B shows Scheme 1 , which is a synthetic path to MIC^iPr»H2CO3. Step i) NBS (N- Bromosuccinimide), L-proline in DCM (Dichloromethane), 0 °C to RT; Step ii) anhyd. EtOH A; Step iii) aq. NaHCOs; Step iv) iPr-l, MeCN, A; Step v) HCOs' resin, MeOH, RT.

Fig. 2A shows optimized deposition conditions for MIC^iPr»H2CO3 on Au.

Fig. 2B shows CV of three samples: bare Au, Au with a SAM of MIC^iPr that was deposited at RT, and Au with a SAM of MIC^iPr that was deposited at 50 °C.

Fig. 2C shows electrochemical impedance spectroscopy (EIS) for: bare Au; Au with a SAM of MIC^iPr that was deposited at RT ; and Au with a SAM of MIC^iPr that was deposited at 50 °C, where Z is impedance, Z_re is real impedance, and Zim is imaginary impedance.

Fig. 2D shows CV of several samples in a study of optimization of deposition time for samples of Au where the precursor MIC^iPr »H2CO3 was used to deposit MIC^iPr on gold. As indicated, the samples included: bare Au, 1 , 2, 15, 24, 36, and 48h of deposition time.

Fig. 3A shows XPS N(1s) region comparing (top) a SAM prepared on a gold substrate under optimized conditions with (bottom) powdered samples of MIC^iPr«H₂CO3.

Fig. 3B shows XPS (Au, C, O, and N, as indicated) analysis of MIC^iPr where deposition was 48 hours at 50 °C.

Fig. 3C shows XPS (Au, C, O, and N, as indicated) analysis of MIC^iPr where deposition was 24 hours at room temperature.

Fig. 3D shows XPS (Au, C, O, and N, as indicated) analysis of MIC^iPr where deposition was 24 hours at 50 °C.

Fig. 4 shows TGA curves for MIC^iPr»H2CO3 (solid line) and NHC^iPr»H2CO3 (dashed line); ramp: 10 °C min-1 , mass loading: 10 ± 2 mg.

Fig. 5A shows a schematic of a replacement attempt between MIC^iPr on an Au surface and CF3-NHC^iPr»H2CO3, which was shown experimentally that MIC was retained on the Au.

Fig. 5B shows F (1 s) XPS region of MIC^iPr on an Au prior to the replacement attempt experiment between MIC^iPr on an Au surface and CF3-NHC^iPr»H2CO3. Fig. 5C shows F (1 s) XPS region of the coating on Au after the replacement attempt experiment between MIC^iPr on an Au surface and CF3-NHC^iPr»H2CO3; notably there is no F peak.

Fig. 5D shows a schematic of an NHC replacement between CF3-NHC^iPr on an Au surface and MIC^iPr ‘F^COs, which was shown experimentally that the CF3-NHC^iPr was replaced by MIC^iPr.

Fig. 5E shows F (1 s) XPS region of CF3-NHC^iPr on an Au prior to the NHC replacement experiment shown in Fig. 5D.

Fig. 5F shows F (1 s) XPS region of the resultant coating on Au after the NHC replacement experiment between CF3-NHC^iPr on an Au surface and MIC^iPr ‘^COs; notably the peak that appeared in Fig. 5E is absent.

Fig. 6A shows XPS spectra for N of MIC^iPr on silver, where the bottom spectrum is the blank MIC^iPr, and the top spectrum is MIC^iPr on silver.

Fig. 6B shows a table of atomic concentrations of MIC^iPr on silver obtained by XPS.

Fig. 7 A shows an XPS spectrum for N 1 s of MIC^iPr on copper.

Fig. 7B shows an XPS spectrum for Cu 2p of MIC^iPr on copper.

DETAILED DESCRIPTION OF EMBODIMENTS

Mesoionic carbenes (MICs) have been developed and tested for their ability to self assemble to form a stable monolayer that is bonded to a substrate’s metallic surface. Referring to Fig. 1A, structural formulae are shown for NHC^iPr on metal (e.g., Au) and MIC^iPr on metal and a list is provided of characteristics of MIC^iPr selfassembled monolayers on metal surfaces. Herein, a metallic surface is represented schematically as a group of spheres as shown in Fig. 1A. In some embodiments, the mesoionic carbene is prepared as a free carbene. However, in some cases, for convenience of preparation and purification, the mesoionic carbenes are prepared as precursors. Mesoionic carbene precursors include anionic counterions. Once the mesoionic carbene bonds to a substrate, its anionic counterion disassociates from the substrate-bound mesoionic carbene monolayer.

In some embodiments, the precursor’s anionic counterion is a halide, hydrogen carbonate, bicarbonate, carbonate, alkylcarboxylate, arylcarboxylate, carboxylate, halide, triflate, pseudohalide, cyanide, or azide, where alkyl is an aliphatic moiety and aryl is aromatic.

Substrates can be composed of one or more materials. In some embodiments, a substrate comprises carbon (e.g., graphene, any of carbon’s forms). In some embodiments, a substrate comprises mica, alumina, silica, titania, silicon, glass, indium tin oxide, or any combination thereof. In some embodiments, a substrate includes a metallic surface. In one embodiment, the substrate is has metal supported on another substance. In one embodiment, the metal is free standing. In one embodiment, the metal is a nanoparticle or nanocluster. Substrates may include one or more metals. Examples of metals include: transition metals, platinum metals and others. Examples may include mixtures of metals and alloys. Non-limiting examples include Fe, Ru, Rh, Ir, Ni, Pd, Pt, Cu, Cr, Ag, Au, W, Mo, Co, or any alloy or other combination thereof. Examples of alloys include steel, brass, bronze, tungsten carbide, calcium carbide, or any combination thereof. Substrates may be a metal chip. An example of a metal chip is a surface plasmon resonance (SPR) detector chip. In an embodiment, a substrate is functionalized with a chemical species that can be displaced by a mesoionic carbene, such as, for example, thio and/or phosphino groups. In one embodiment, a method for forming a composite material comprises a mesoionic carbene monolayer and a substrate, wherein the mesoionic carbene monolayer bonds to the substrate and is stable. In one embodiment of this method, the substrate includes a metallic surface.

Structural formula for mesoionic carbene precursors are shown below in Formula (1):

where X is a counterion,

Rbackbone is H, a substituted or unsubstituted linear, branched or cyclic aliphatic moiety, a substituted or unsubstituted aromatic moiety, a heteroatom, a moiety that includes a transition metal, or any combination thereof; and

Rwingtip is a substituted or unsubstituted linear, branched or cyclic aliphatic moiety, a substituted or unsubstituted aromatic moiety, or any combination thereof.

A “substituent” is an atom or group of bonded atoms that can be considered to have replaced one or more hydrogen atoms attached to a parent molecular entity. Examples of substituents include alkyl, alkenyl, alkynyl, aryl, aryl-halide, heteroaryl, cycloalkyl (non-aromatic ring), Si(alkyl)s, Si(alkoxy)3, halo, alkoxyl, amino, alkylamino, alkenylamino, amide, amidine, hydroxyl, thioether, alkylcarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carbonate, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphate ester, phosphonato, phosphinato, cyano, acylamino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, dith iocarboxyl ate, sulfate, sulfato, sulfonate, sulfamoyl, sulfonamide, nitro, nitrile, azido, heterocyclyl, ether, ester, silicon-containing moieties, thioester, or a combination thereof. The substituents may themselves be substituted. For instance, an amino substituent may itself be mono or independently disubstituted by further substituents defined above, such as alkyl, alkenyl, alkynyl, aryl, aryl-halide and heteroaryl cycloalkyl (non-aromatic ring).

As used herein, “aliphatic” refers to hydrocarbon moieties that are linear, branched or cyclic, may be alkyl, alkenyl or alkynyl, and may be substituted or unsubstituted. “Alkenyl” means a hydrocarbon moiety that is linear, branched or cyclic and contains at least one carbon to carbon double bond. “Alkynyl” means a hydrocarbon moiety that is linear, branched or cyclic and contains at least one carbon to carbon triple bond.

In some embodiments, Rwingtip is an iso-propyl moiety. In some embodiments, Rwingtipis a benzyl moiety. In some embodiments, Rbackbone is H, O-(Ci-Ce-aliphatic), OCHs, CF₃, or alkylferrocene. In some embodiments, Rbackbone provides a functional moiety. An example of a functional moiety is ferrocene. In some embodiments, Rbackbone provides sensing capabilities while the carbene provides a strong electrochemically stable bond to a substrate. In some embodiments, Rbackbone provides a functional moiety that can be reacted with other compounds.

By this technique, other compounds can become bound to the substrate through the mesoionic carbene. In this way, other compounds can become covalently attached to the carbene, while the carbene provides a strong electrochemically stable bond to a substrate. In this way, the mesoionic carbene monolayer provides a mechanism to attach functional moieties (i.e. , compounds that are useful) to the carbene-bound substrate. In one embodiment, the monoloayer acts analogously to a paint primer, where further layers bond well to it. Uses for such functional moieties include: corrosion protection; sensors; detecting, sensing, molecular electronics, biosensors, surface patterning, protecting metals in microelectronic devices, drug delivery, or sensing applications. Representative examples of mesoionic carbene precursors are show in Table 1 and include:

1 .3-di isopropyl- 1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (MIC^iPr»HI);

1.3-diisopropyl-1/7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (MIC^iPr»H2CO3);

1 .3-diisopropyl-6-methoxy-1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (^OMeMIC^iPr»HI);

1 .3-diisopropyl-6-methoxy-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (OMe_M|c^iPr» H2CO3);

1 .3-diisopropyl-6-(trifluoromethyl)-1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (^CF3MIC^iPr,HI);

1 .3-diisopropyl-6-(trifluoromethyl)-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (^CF3MIC^iPr»H2CO3);

1 .3-dibenzyl-1 H-imidazo[1 ,2-a]pyridin-4-ium bromide (MIC^Bz*HBr);

1.3-dibenzyl-1 H-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (MIC^Bz»H2CO3); 6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (^OHexMIC^iPr»HI); 6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (^OHexMIC^iPr«H2CO₃);

6-((6-Ferrocenohexyl)oxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridin-1-ium (^OHexFcMIC^iPr«H2CO₃); or

1 .3-diisopropyl-6-(prop-2-yn-1 -yloxy)-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (^OProP^ar9y^|MIC^iPr«H₂C03).

The mesoionic carbene precursors of Formula (1 ), which are salts with anionic counterions, provide mesoionic carbenes of that self-assemble into monolayers (SAM) or overlayers. Once bound to a substrate, the mesoionic carbenes are no longer associated with the anionic counterion that is present in Formula (1 ). Instead, they are present as the positively charged mesoionic carbene moiety (see Formula (2).

(2), wherein Rbackbone and R_Wingti_P are defined in Formula (1 ).

Formula (3) shows attachment of the mesoionic carbene to the substrate, which is represented by a wiggly line.

wherein Rbackbone and R_Wingti_P are defined above.

In one embodiment, a method for forming a self-assembled monolayer is provided that comprises a mesoionic carbene of Formula (2) on a surface of a substrate, wherein the mesoionic carbene bonds to the surface (i.e., chemisorbs). In one embodiment, the surface includes a metallic surface.

In numbering ring atoms of a carbene, one of the heteroatoms is atom 1 , and the numbering goes around the ring in the direction of the other heteroatom; so a carbon that is located in the ring in between two heteroatoms is known as C2.

The structural formulae of general Formulas (1 ) and (2) are considered to be abnormal carbenes. Abnormal refers to which carbon, of the carbene, has a bond to a substrate. If this atom is the C2 atom, as shown in (a) below, then the carbene is “normal”. If the atom that is bound to the substrate is not the C2 atom, but a different atom of the carbene such as C5 as shown in (b) below, then it is referred to as “abnormal” (Crabtree, R.H., Coord. Chem. Rev. 257(2013) 755-766).

Since a first report of N-heterocyclic carbenes (NHCs) as ligands for gold surfaces, the use of these ligands on metallic and non-metallic surfaces, has attracted considerable attention. NHC-based self-assembled monolayers (SAMs) are an emerging class of ligands for surfaces including metal surfaces. The stronger surface binding energies of NHCs compared to the other classic ligands and their high potential for tunability positions NHCs as ideal candidates for producing the next generation of nanomaterials.

Mesoionic carbenes (MICs) are superior o-donors compared to NHCs and are powerful ligands in organometallic chemistry. A synthetic route was developed (see Scheme 1 in Fig. 1 B). As described herein, studies were conducted to investigate this important class of carbene as ligands for self-assembled monolayers.

As described herein, SAMs of MICs were prepared on Au, Ag and Cu. These are representative examples of surfaces and should not be limiting.

SAMs of MIC^iPr were prepared on Au by immersing Au/Si samples in a 10 mM MeOH solution of MIC^iPr»H2CO3 at room temperature for 24 h. Although N 1 s XPS analysis suggested that some deposition had occurred under these conditions (see Figs. 3A-3D), studies using cyclic voltammetry (CV, see Figs. 2B and 2D) and electrochemical impedance spectroscopy (EIS, see Fig. 2C) showed no current suppression or increase in impedance, respectively. However, increasing the deposition temperature to 50 °C and time to 48 h yielded SAMs with significant reduction in current and notable increase in resistance, as determined by CV and E IS , respectively, consistent with the formation of SAMs on the surface (see Figs. 2B-2D). Referring to Fig. 2D, CV of several samples are shown from a study to optimize deposition time for samples of Au where the precursor MICiPr »H2CO3 was used to deposit MIC^iPr on gold. The time points of 36h, and 48h of deposition time yielded SAMs with significant reduction in current, as shown.

XPS analysis was employed to provide more insight into monolayer formation. The XPS spectrum was examined of the powdered MIC^iPr»H2CO3 starting material (see Fig. 3A), which was characterized by two signals in equal intensity assigned to the pyridyl and imine groups, at 401 .6 eV and 400.6 eV respectively. XP spectra of SAMs resulting from deposition of MIC^iPr»H2CO3 under optimized conditions also displayed two signals of equal intensity centered at 400.7 eV and 399.2 eV. The shift in the binding energy and increase in the FWHM for both signals suggested a change in the electronics of the ligand upon binding to gold, and data strongly support the formation of an MIC^iPr SAM under these conditions.

Stability studies were conducted where SAMs of MIC^iPr were subjected to a variety of conditions including pH extremes (pH 2, pH 12), refluxing water, and room temperature an aqueous 1 % hydrogen peroxide solution for 24 hours. During these treatments, the MIC^iPr SAM showed minimal changes to the overall monolayer, as illustrated when comparing XPS signals in high resolution scans of C (1s), O (1s) and N (1 s). To further probe the stability of these SAMs, MIC^iPr SAMs and NHC^iPr SAMs were exposed to pH 12 for 5 days. Analysis of the surface via time-of-f light secondary ion mass spectrometry (ToF-SIMS) showed virtually no loss of MIC^iPron the surface even after exposure to these harsh conditions, while NHC^iPr was no longer observed.

Co-deposition experiments were carried out to study the propensity for the two types of carbene to deposit on a bare gold surface. See Example 4 for details. The average ratio between MIC^iPr and CF3-NHC^iPr was calculated to be 4:1 , which demonstrated preferential formation of SAMs from MIC^iPr in comparison with CF3- NHC^iPr.

A comparison was conducted of the ability of one NHC to replace the other when present on the surface as a preformed SAM. SAMs of MIC^iPr were prepared on Au/Si surfaces and treated with CF3-NHC^iPr»H2CO3, using the trifluoromethyl unit as an XPS reporter (see Fig. 5A-5F). Typically, SAMs composed of benzannulated NHCs such as NHC^iPr are deposited over 24 h at room temperature, and so these conditions were employed to test the stability of MIC^iPr vs. replacement with NHC^iPr. However, after exposure to these conditions, no NHC was incorporated as determined by analysis of fluorine content in the F 1 s region (see Figs. 5A-5F). This result indicated that the MIC^iPr SAM resisted the incorporation of CF3-NHC^iPr within the error of XPS measurements.

To test the reverse reaction, SAMs prepared from CF3-NHC^iPr were treated with MIC^iPr»H2CO3 to look for loss or retention of fluorine. This experiment resulted in the complete removal of fluorine from the surface, as determined by XPS (see Fig. 5A- 5F).

This experiment required elevated temperatures and longer deposition times to ensure generation of MIC^iPr from its bicarbonate salt, and so an additional set of experiments was performed in which MIC^iPr SAMs were treated with CFs- NHC^iPr»H2CO3 at elevated temperatures and longer periods of time. Under these more forcing conditions, fluorine was observed by XPS analysis, but the replacement of MIC for NHC was not substantial. Treatment of the MIC^iPr with CF3-NHC^iPr»H2CO3 at RT for 48 h, resulted in the incorporation of one CF3-NHC^iPr for every six MIC^iPr units. At 50 °C for 48 h, one CF3-NHC^iPr was incorporated for every five MIC^iPr units on Au. These results illustrated that MICs form more robust SAMs than those generated from typical NHCs, presumably due to stronger carbon-metal bonds on surfaces.

Contact angle measurements were also performed for Au/Si substrates functionalized by MIC^iPr and NHC^iPr (see Table 5). Compared to bare Au (67 ± 2°), the surface hydrophobicity did not change substantially upon the surface adsorption of MIC^iPr (72 ± 2°) and NHC^iPr (71 ± 2°).

A straightforward synthetic route to the MIC precursor MIC^iPr»H2CO3 was developed and its deposition on Au was thoroughly studied. Preliminary results of MIC^iPr monolayers on copper and silver are also described herein. Under optimized conditions, MIC^iPr»H2CO3 was deposited on Au, resulting in the formation of a new MIC-on metal SAM. Solution deposition conditions were optimized using electrochemical methods to monitor the successful formation of a stable monolayer. Monolayer stability was confirmed by multiple CV cycles and extreme potential range, concluding that solution deposition at 50°C for 48 h was optimal.

Direct comparison of the two types of SAMs was accomplished through a comparison of stability under extreme conditions, competitive deposition, and treatment of preformed monolayers with carbene precursors. These studies showed that MIC-based SAMs resist NHC incorporation, and NHC-based SAMs are replaced with MICs. When co-deposited, MICs out compete NHCs. Finally, MIC- based SAMs were found to be more robust to long term immersion in base.

To gain a better understanding of the invention described herein, the following working examples are set forth. Examples of mesoionic carbenes having general formula 1 are described herein (see Table 1 for structural formula, chemical names and abbreviated names). Synthesis and characterization data for mesoionic carbenes is presented in the examples. In addition, details of successful application of mesoionic carbenes on metallic surfaces are provided. It should be understood that these examples are for illustrative purposes only. Therefore, they should not limit the scope of this invention in any way.

Examples

Unless otherwise stated, all solvents (including NMR solvents) and reagents were obtained from Sigma-Aldrich and used without further purification. Ethanol (anhydrous grade, Greenfield Global Commercial Alcohols) was stored as-is over oven dried (150 °C) molecular sieves (3 A, Alfa Aesar) prior to use. Using previously established methods (see Nature Chemistry (2014), vol. 6, pages 409-414), hydrogen carbonate exchange resin was prepared by treating Amberlyst A26 hydroxide resin treated with carbon dioxide prior to use.

¹H, ¹³C{¹H} and ¹⁹F{¹ H} NMR spectra were recorded at Queen’s University using Bruker Avance-500, 600 or 700 MHz spectrometers at 298 K. Chemical shifts (5) are reported in parts per million (ppm) and are referenced to residual protonated (¹H) or deuterated (¹³C{¹H}) solvent signals. ¹⁹F{¹ H} NMR spectra are referenced to an external CFCh standard (5F = 0 ppm). Coupling constants (J) are reported as absolute values. All NMR data were processed and displayed using Bruker TopSpin software. Elemental analyses were performed at Queen’s University using Flash 2000 CHNS-0 analyzer. Electrospray ionization mass spectra (ESI-MS) of small molecules were recorded at Queen’s University using a Thermo Fisher Orbitrap VelosPro mass spectrometer with a heated-electrospray ionization probe.

All electrochemical experiments were carried out using a CHI6055E Electrochemical Analyzer potentiostat. All electrochemical experiments were performed using a three-electrode electrochemical cell set-up with 2 mm diameter gold disc working electrode. Ag/AgCI in 3 M KCI was used for a reference electrode, a platinum wire as counter/auxiliary electrode, and a salt bridge was used to allow free flow of ions between one cell to the other. The salt bridge was built using a 4 mm glass rod filled with a heated 2-5% agar solution in 1 M KNOs (w/v) and stored in 1 M KNO3 solution. All electrochemical data were processed with OriginPro 2016 software.

XP spectra were recorded on a Kratos Nova AXIS spectrometer equipped with AIN X-ray source. Samples were mounted on an aluminum sample holder using double-sided adhesive copper tape and kept under high vacuum (10^-8 Torr) overnight inside the preparation chamber before being transferred to the analysis chamber (ultra-high vacuum, 10^-10 Torr). Data were collected using Al Ka radiation operating at 1486.69 eV (150 W, 15 kV), charge neutralizer and a delay-line detector (DLD) consisting of three multichannel plates. Acquired data were processed using CasaXPS software following reference handbooks. Processed data were plotted in Python using the Matplotlib package. Elemental compositions of samples were evaluated by running wide scan at 160 eV pass energy. After peak identification, high resolution scans were performed for O1s, C1s, N1s, and substrate of interest region. These scans were performed at 20 eV pass energy. Au 4f spectra were peak fitted following guidelines from reference handbooks (Zhukhovitskiy, A. V., et al., Chem. Rev. 2015, 115 (20), 11503-11532, and

Jiang, L., Chem. Sci. 2017, 8 (12), 8301-8308) and peak was charge corrected to 84 eV with spin-orbit coupling of ~3.7 eV. Unless otherwise specified, a Shirley type background correction was used for all spectra shown here.

Samples were examined using an ION-TOF (GmbH) ToF-SIMS IV equipped with a Bi cluster liquid metal ion source. A pulsed 25 keV Bi³⁺ cluster primary ion beam was used to bombard the surface of the samples to generate secondary ions with a current of 1.5 pA. The positive (and negative) secondary ions were extracted from the sample surface, mass separated and detected via a reflectron-type of time- of-flight analyzer. Reflector values for the positive and negative mode were + 16V and - 34V, respectively. Sample charging was neutralized with a pulsed, low energy electron flood. Ion mass spectra were collected in an area of 500 pm x 500 pm at 128 x 128 pixels with 25 scans. Mass spectra were processed on ION-TOF software with a binning value of 256 and calibrated to H, C and C2H5 mass signals.

A MIC precursor MIC^iPr»HI was prepared using classical a-halocarbonyl chemistry (Adams, R., et al., J. Am. Chem. Soc. 1958, 80 (17), 4618-4620). Isovaleraldehyde was a-brominated using N-bromosuccinimide to afford 4 in 57% yield (see Scheme 1 in Fig. 1 B). Reaction times longer than 2 h resulted in lower yields because of the reactive nature of a-halocarbonyl species, and thus 4 was used immediately without isolation. Reaction between an excess of 4 and 2- aminopyridine derivatives in refluxing ethanol afforded imidazo[1 ,2-a]pyridinium bromide salts 5»HBr in up to 98 % yield. Excesses of 4 were needed to prevent contamination with unreacted 2-aminopyridine. Analytically pure 5»HBr could be isolated directly from the reaction mixture by first removing ethanol in vacuo, then suspending the resulting solids in diethyl ether and vacuum filtration. The route was amenable to the introduction of substituents on the backbone as needed (R = H, CF₃, OMe).

Alkylation of 5 with 2-iodopropane afforded MIC^iPr»HI in 82% yield. Reaction between MIC^iPr»HI and strong bases (NaN(SiMe₃)2, LiN(iPr)2, KH) resulted in decomposition, and attempts to trap the transient carbene with CO2 to isolate a carboxylate derivative were unsuccessful. These difficulties led us to prepare the hydrogen carbonate salt MIC^iPr»H2CO₃, which could be isolated in 78 % yield as a monohydrate salt after HCO₃ resin exchange.

2-Bromo-3-

2-Bromo-3-methylbutanal (4) was prepared following a modified literature procedure and used without isolation (Larrea, C. R., et al., Chem. Phys. Chem. 2017, 18 (24), 3536-3539). A 500 mL round bottom flask was equipped with a PTFE- coated stir bar and 150 mL of CH2CI2. Using an ice-water bath, the solvent was cooled to 0 °C before adding N-bromosuccinimide (17.8 g, 100 mmol, 1.3 eq) and L- proline (2.61 g, 23 mmol, 0.3 eq.). The round bottom flask was sealed with a septum and placed under an argon atmosphere. The red-orange coloured mixture was left to stir at 0 °C for 5 minutes before adding isovaleraldehyde (8.3 mL, 75 mmol, 1 eq.) drop-wise to the reaction mixture. The reaction mixture was left to warm to room temperature and was stirred under an argon atmosphere for 2 h. During this time, the colour of the reaction changed from red-orange, to pale yellow, before finally returning to red-orange. The reaction mixture was then concentrated to ca. 75 mL by rotary evaporation before adding 150 mL of hexanes to precipitate succinimide, L- proline and other impurities. The precipitates were removed by filtration through a

2.5 cm silica gel plug, washing with hexanes (3 x 50 mL). The colourless filtrate was then concentrated by rotary evaporation while maintaining the bath temperature below 40 °C, to afford the desired product as a pale yellow coloured oil (7.06 g, 57 %). ¹H NMR (CDCh, 700 MHz): 5 9.43 (d, ³JHH = 3.8 Hz, 1 H, HCO), 4.06 (dd, ³JHH =

6.6 Hz, ³JHH = 3.8 Hz, 1 H, CHBr), 2.23 (oct, ³JHH = 6.6 Hz, 1 H, CH(CH₃)₂), 1 .09 (d, ³JHH = 6.6 Hz, 3H, CH₃), 1 .07 ppm (d, ³JHH = 6.6 Hz, 3H, CH₃). ¹³C{¹H} NMR (CDCh, 175 MHz): 5 193.5, 63.8, 30.2, 20.4, 19.5 ppm. Spectroscopic data were consistent with the literature (Larrea, C. R., et al., Chem. Phys. Chem. 2017, 18 (24), 3536- 3539).

General procedure for the preparation of 3-isopropylimidazo[1 ,2-a]pyridinium bromides

Crude 2-bromo-3-methylbutanal as prepared above was immediately dissolved in 50 mL anhydrous ethanol and combined with the desired 2- aminopyridine. A condenser was added, and the yellow coloured solution was heated to 80 °C for 20 h while open to air. After cooling to room temperature, the volatiles were removed by rotary evaporation. The resulting pale yellow coloured solid was suspended in 100 mL of diethyl ether and triturated to afford a colourless precipitate and pale yellow supernatant. The precipitate was isolated by vacuum filtration, washing with diethyl ether (3 x 25 mL) to afford the desired product as a pale yellow coloured powder which was dried in vacuo overnight.

3-i

2-alpyridinium bromide (5*

Prepared following the general procedure above using 2-bromo-3- methylbutanal (6.3 g, 43 mmol, 1.2 eq.) and 2-aminopyridine (2.84 g, 30 mmol, 1 eq.). Product was obtained after drying in vacuo for 18 h (7.3 g, >99 %). ¹H NMR

(CDCh, 700 MHz): 5 15.1 (s, 1 H, NH), 8.40 (s, br, 1 H), 8.36 (d, ³JHH = 9.3 Hz, 1 H),

7.81 (t, ³JHH = 8.0 Hz, 1 H), 7.54 (d, JHH = 2.7 Hz, 1 H, NCH), 7.46 (t, ³JHH = 7.0 Hz,

1 H), 3.35 (sept, ³JHH = 6.8 Hz, 1 H, CH), 1 .44 ppm (d, ³JHH = 6.8 Hz, 6H, CH₃).

¹³C{¹H} NMR (CDCh, 175 MHz): 5 139.8, 132.8, 132.2, 125.1 , 117.5, 117.4, 114.3, 24.0, 20.5 ppm. Anal. calc, for C Hi₃N₂Br: C, 49.81 ; H, 5.43; N, 11.62. Found: C, 49.60; H, 5.38; N, 11.57. ESI-HRMS (m/z): Calc, for CIOHI₃N₂ ⁺: 161 .1074; found 161.1069.

3-isopropyl-6-trifluoromethylimidazo[1 ,2-a]pyridinium bromide

Prepared following the general procedure above using 2-bromo-3- methylbutanal (1.2 g, 7.4 mmol, 1.2 eq.) and 2-amino-5-trifluoromethylpyridine (1.0 g, 6.1 mmol, 1.0 eq.). Product was obtained after drying in vacuo for 18 h (1.1 g, 60 %).¹H NMR (600 MHz, CDCI₃) 5 8.69 (d, J = 9.4 Hz, 1 H), 8.61 (p, J = 1.1 Hz, 1 H), 7.98 (dd, J = 9.4, 1 .6 Hz, 1 H), 7.80 (d, J = 1 .0 Hz, 1 H), 3.46 - 3.37 (m, 1 H), 1 .53 (d, J = 6.8 Hz, 6H). ¹³C NMR (151 MHz, CDCI3) 5 140.15, 134.11 , 127.81 , 123.33, 122.26, 119.47, 115.92, 24.02, 20.53.¹⁹F NMR (470 MHz, CDCI3) 5 -62.31. ESI- HRMS (m/z): Calc, for CnHi2F₃N2⁺: 229.10; found 229.09.

3-isopropyl-6-methoxyimidazo[1 ,2-alpyridinium bromide

Prepared following the general procedure above using 2-bromo-3- methylbutanal (2.3 g, 14 mmol, 1.2 eq.) and 2-amino-5-methoxypyridine (1.5 g, 12 mmol, 1.0 eq.). The product was obtained after drying in vacuo for 18 h (2.9 g, 90 %). ¹H NMR (500 MHz, CDCI3) 5 14.50 (s, 1 H, N/7), 8.09 (d, J = 7.5 Hz, 1 H), 7.63 (d, J = 2.5 Hz, 1 H), 7.30 (d, J = 2.6 Hz, 1 H), 7.00 (dd, J = 7.5, 2.5 Hz, 1 H), 3.99 (s, 3H, O-CH3), 3.21 (hept, J = 6.8 Hz, 1 H, CH-(CH₃)₂), 1 .40 (d, J = 6.8 Hz, 6H, CH- (CH₃)₂). ¹³C NMR (126 MHz, CDCI3) 6 162.84, 142.49, 131.55, 125.42, 116.20, 112.08, 92.37, 77.42, 77.16, 76.91 , 57.17, 23.84, 20.67. ESI-HRMS (m/z): Calc, for CII HI₅N₂O⁺: 191.12; found 191.11774.

General procedure for the preparation of 1 ,3-diisopropylimidazo[1 ,2-alpyridinium iodides

Pretreatment: A solution of desired 3-isopropylimidazo[1 ,2-a]pyridinium bromide in CHCh (100 mL) was prepared and transferred to a separatory funnel. The yellow coloured organic solution was washed with a saturated aqueous NaHCOs solution (2 x 50 mL), followed by a saturated NaCI solution (50 mL). After separating the aqueous and organic portions and removing the CHCh by rotary evaporation, 3- isopropylimidazo[1 ,2-a]pyridine was obtained as an orange coloured oil and used immediately without further isolation.

N-alkylation: 3-isopropylimidazo[1 ,2-a]pyridin derivatives, as prepared above, were dissolved in acetonitrile (100 mL) and combined with 2-iodopropane in a 250 mL round bottom flask. A magnetic stir bar was added before fitting a water-cooled condenser and heating to 85 °C for 20 h while open to air. After cooling to room temperature, the volatiles were removed by rotary evaporation, yielding a yellow coloured residue which was suspended in an acetone/diethyl ether mixture (1 :1 , 40 mL). After sonication/trituration, the colourless precipitate was collected by vacuum filtration and washed with diethyl ether (3 x 20 mL) to afford the desired product as a pale yellow coloured powder.

1 ,3-dii -1/7-imi

idin-4-ium iodide

Prepared following the general procedure above using 3- isopropylimidazo[1 ,2-a]pyridinium bromide (6.03 g, 25 mmol, 1 eq.), 2-iodopropane (7.5 mL, 75 mmol, 3.0 eq.). Product was obtained after drying in vacuo for 18 h (6.79 g, 82%). ¹H NMR (CDCb, 500 MHz): 5 8.73 (d, ³JHH = 7.0 Hz, 1 H), 8.42 (d, ³JHH = 9.1 Hz, 1 H), 8.01 (t, ³JHH = 8.0 Hz, 1 H), 7.82 (s, 1 H), 7.60 (t, ³JHH = 7.0 Hz, 1 H), 5.37 (sept, ³JHH = 6.7 Hz, 1 H), 3.53 (sept, ³JHH = 6.8 Hz, 1 H), 1 .70 (d, ³JHH = 6.7 Hz, 6H), 1.49 ppm (d, ³JHH = 6.8 Hz, 6H). ¹³C{¹H} NMR (CDCb, 125 MHz): 5 138.4, 134.0, 133.6, 127.0, 118.2, 117.4, 112.7, 51.1 , 24.4, 22.9, 20.8 ppm. Anal. calc. for Ci3Hi₉N₂l: C, 47.29; H, 5.80; N, 8.48. Found: C, 47.24 H, 5.77; N, 8.44. ESI- HRMS (m/z): Calc, for CI₃HI₉N₂ ⁺: 203.1543; found 203.1534.

1 ,3-diisopropyl-6-trifluoromethylimidazo[1 ,2-a] pyridin-4-ium iodide

Prepared following the general procedure above using 3-isopropyl-6- trifluoromethylimidazo[1 ,2-a]pyridinium bromide (2 g, 6.4 mmol, 1 eq.), 2- iodopropane (5.3 mL, 27 mmol, 4.3 eq.). Analytically pure material was obtained after drying in vacuo for 18 h (1.2 g, 48%). ¹H NMR (600 MHz, CDCb) 5 8.98 (d, J = 9.6 Hz, 1 H), 8.65 (s, 1 H), 8.09 (d, J = 1.0 Hz, 1 H), 8.08 (dd, J = 9.6, 1.6 Hz, 1 H), 5.58 (hept, J = 6.7 Hz, 1 H), 3.56 - 3.46 (m, 1 H), 1 .73 (d, J = 6.7 Hz, 6H), 1 .54 (d, J = 6.8 Hz, 6H). ¹³C NMR (151 MHz, CDCI3) 5 138.70, 135.15, 128.78, 124.29, 122.23, 119.68, 115.43, 52.19, 24.42, 22.87, 20.63. ¹⁹F NMR (470 MHz, CDCb) 5 -62.91 . ESI-HRMS (m/z): Calc, for Ci4Hi₈F₃N₂ ⁺:271 .14; found 271.13962.

1 ,3-diisopropyl-6-i

2-alpyridin-4-ium iodide

Prepared following the general procedure above using 3-isopropyl-6- methoxyimidazo[1 ,2-a]pyridinium bromide (2.0 g, 7.4 mmol, 1.0 eq.), 2-iodopropane (6.1 mL, 31 mmol, 4.3 eq.). The product was obtained after drying in vacuo tor 18 h (1.7 g, 24%). ¹H NMR (500 MHz, CDCh) 5 8.45 (d, J = 7.5 Hz, 1 H), 7.82 (d, J = 2.4 Hz, 1 H), 7.38 (d, J = 1 .0 Hz, 1 H), 7.08 (dd, J = 7.6, 2.4 Hz, 1 H), 5.60 (hept, J = 6.7 Hz, 1 H), 4.20 (s, 3H), 3.43 - 3.34 (m, 1 H), 1.59 (d, J = 6.6 Hz, 6H), 1 .41 (d, J = 6.8 Hz, 6H). ¹³C NMR (126 MHz, CDCI3) 5 163.90, 141.20, 132.80, 127.16, 127.11 , 115.20, 112.31 , 92.22, 77.41 , 77.16, 76.91 , 59.51 , 50.39, 24.08, 22.70, 20.86. ESI- HRMS (m/z): Calc, for Ci₄H2iN₂O⁺: 233.17; found 233.16324.

General procedure for the preparation of 1 ,3-diisopropylimidazo[1 ,2-a]pyridinium hydrogen carbonates

Using a modified and previously described procedure (Crudden, C. M., et al., Nat. Commun. 2016, 7, 12654). 1 ,3-diisopropyl-1 /7-imidazol[1 ,2-a]pyridin-4- ium hydrogen carbonate can be prepared from either iodide or triflate salt precursors. A representative procedure using the iodide salt is given below.

1 ,3-diisopropyl-1/7-imidazol[1 ,2-a]pyridin-4-ium iodide salt (1 eq.) was dissolved in 10 mL of methanol and added to freshly prepared HCOs' resin (3 eq.). The pale yellow coloured mixture was stirred for 30 minutes before removing the resin by vacuum filtration. The resin was washed with methanol (3 times) before discarding. The methanolic filtrate was dried under a stream of air overnight to afford a pale yellow coloured solid. The solids were treated by sonication/trituration in acetone (1 x 10 mL) and diethyl ether (2 x 10 mL), removing the yellow coloured supernatant each time before drying in vacuo to give the desired product as a colourless powder.

1 ,3-dii

2-alpyridin-4-ium

carbonate

Prepared following the general procedure above using 1 ,3-diisopropyl-1 H- imidazo[1 ,2-a]pyridin-4-ium iodide (0.4 g, 1.2 mmol, 1 eq.), HCOs' resin (4.8 mL, 3 eq.). The product was obtained after drying in vacuo tor 18 h. Elemental analysis and thermogravimetric analysis indicate that the product was obtained as a monohydrate. (0.22 g, 78 %). ¹H NMR (600 MHz, MeOD) 5 8.78 (dt, J = 6.9, 1.1 Hz, 1 H), 8.15 (dt, J = 9.3, 1.1 Hz, 1 H), 8.10 (d, J = 1.0 Hz, 1 H), 8.01 (ddd, J = 9.3, 7.0, 1.1 Hz, 1 H), 7.55 (td, J = 6.9, 1.1 Hz, 1 H), 5.09 (hept, J = 6.7 Hz, 1 H), 3.47 (pd, J = 6.9, 1.0 Hz, 1 H), 1.64 (d, J = 6.7 Hz, 6H), 1.47 (d, J = 6.9 Hz, 6H). ¹³C NMR (151 MHz, MeOD) 5 160.03, 138.72, 133.94, 132.83, 126.69, 116.96, 110.85, 50.03, 23.66, 20.87, 19.37. Anal. calc. for Ci₄H2oN20₃ (+ H₂O): C, 59.56; H, 7.85; N, 9.92. Found: C, 59.49; H, 7.83; N, 9.92. ESI-HRMS (m/z): Calc, for Ci3Hi₉N₂ ⁺: 203.1543; found 203.15376.

1 ,3-diisopropyl-6-methoxyimidazo[ 1 ,2-a]pyridin-4-ium hydrogen carbonate

Prepared following the general procedure above using 1 ,3-diisopropy I-6- methoxyimidazo[1 ,2-a]pyridin-4-ium iodide (0.4 g, 1.2 mmol, 1 eq.), HCO₃' resin (4.8 mL, 3 eq.). The product was obtained after drying in vacuo for 18 h. (0.12 g, 36 %). ¹H NMR (600 MHz, MeOD) 5 8.58 (dd, J = 7.6, 2.0 Hz, 1 H), 7.87 (d, J = 1.0 Hz, 1 H), 7.45 (d, J = 2.6 Hz, 1 H), 7.17 (dd, J = 7.6, 2.4 Hz, 1 H), 5.05 - 4.97 (m, 1 H), 4.10 (d, J = 1 .3 Hz, 3H), 3.38 (p, J = 6.7 Hz, 1 H), 1 .62 (d, J = 6.6 Hz, 6H), 1 .45 (d, J = 6.8 Hz, 6H). ¹³C NMR (151 MHz, MeOD) 5 163.91 , 141.14, 132.94, 127.44, 115.38, 110.84, 89.59, 56.30, 49.22, 23.52, 20.67, 19.51. ESI-HRMS (m/z): Calc, for CI₄H₂I N₂O⁺: 233.17; found 233.16304.

1 ,3-diisopr carbonate

Prepared following the general procedure above using 1 ,3-diisopropy I-6- trifluoromethylimidazo[1 ,2-a] pyridin-4-ium iodide (0.4 g, 1.0 mmol, 1 eq.), HCO₃ ^_ resin (4.0 mL, 3 eq.). Product was obtained after drying in vacuo for 18 h. (0.18 g, 53 %). ¹ H NMR (500 MHz, MeOD) 5 9.24 (s, 1 H), 8.36 (d, J = 9.6 Hz, 1 H), 8.29 (s, 1 H), 8.22 (dd, J = 9.5, 1 .6 Hz, 1 H), 5.16 (p, J = 6.7 Hz, 1 H), 3.59 (h, J = 6.6 Hz, 1 H), 1 .66 (d, J = 6.6 Hz, 6H), 1.47 (d, J = 6.8 Hz, 6H). ¹³C NMR (126 MHz, MeOD) 5 160.62, 140.58, 137.27, 129.65, 127.59, 125.18, 119.96, 113.77, 52.22, 24.92, 22.25, 20.96. ¹⁹F NMR (470 MHz, CDCI3) 5 -63.49. ESI-HRMS (m/z): Calc. for CI₄HI₈F₃N2⁺:271 .14; found 271.13977.

Synthesis of 5-(hexyloxy)pyridin-2-amine

To a stirred solution of 6-aminopyridin-3-ol (0.410 g, 3.723 mmol) in DMSO (20 mL) was added tBuONa (0.375 g, 3.90 mmol) under argon. The resulting suspension was stirred for 10 min at room temperature followed by dropwise addition of 6-bromohexane (0.50 mL, 3.9 mmol). The reaction mixture was stirred overnight at 80 °C and an orange suspension was present. The reaction mixture was cooled down to room temperature and quenched with water. The organic layer was extracted by EtOAc, dried over Na2SO4 and concentrated under reduced pressure by rotary evaporator. A crude product was purified by flash column chromatography (silica gel; EtOAc/CHsOH, 10:1 ) and afforded a pure compound as a dark red oil (0.452 g, 65%). ¹H NMR (CDCb, 400 MHz): 5 7.88 (d, ³JHH = 5.9 Hz, 1 H, Ar-H), 6.25 (d, ³JHH = 5.9 Hz, ³JHH = 2.9 Hz, 1 H, Ar-H), 5.97 (d, ³JHH = 2.0 Hz, 1 H, Ar-H), 4.34 (s, br, 1 H, -NH₂), 3.94 (t, ³JHH = 6.6 Hz, 2H, O-CH2-), 1 .82-1 .64 (m, 2H, -CH2-), 1 .50- 1.24 (m, 6H, -CH2-), 0.90 (t, ³JHH = 6.8 Hz, 3H, CH₃) ppm. ¹³C{¹H} NMR (CDCb, 101 MHz): 5 166.9 (Ar-H), 160.0 (Ar-H), 149.1 (Ar-H), 103 (Ar-H), 93.0 (Ar-H), 67.7 (- CH2-), 31.5 (-CH2-), 28.9 (-CH2-), 25.6 (-CH2-), 22.5 (-CH2-), 14.0 (-CH3-) ppm. ESI- HRMS (m/z): calcd for C11H18N2O, 194.1419; found, 194.1409.

Synthesis of 6-(hexyloxy)-3-isopropylimidazo[1 ,2-alpyridine

To a stirred solution of 5-(hexyloxy)pyridin-2-amine (0.248 g, 1.27 mmol) in EtOH (10 mL) was added 2-bromo-3-methylbutanal (0.252 g, 1.52 mmol) under argon. The resulting solution was stirred overnight at 80 °C where a dark orange solution waspresent. After cooling to room temperature, volatiles were removed under reduced pressure by rotary evaporation. The resulting solid was dissolved in CHCb (100 mL) and transferred to a separatory funnel. The organic solution was washed with a saturated aqueous NaHCOs solution (2 x 50 mL), followed by a saturated NaCI solution (50 mL). After separating the aqueous and organic portions and removing the CHCb by rotary evaporation, 6-(hexyloxy)-3-isopropylimidazo[1 ,2- a]pyridine was obtained as an yellow coloured oil and used immediately without further purification (0.172 g, 52%).¹H NMR (CDCb, 400 MHz): 5 7.77 (d, ³JHH = 7.6 Hz, 1 H, Ar-H), 7.22 (s, br, 1 H, Ar-H), 6.90 (m, 1 H, Ar-H), 6.56 (dd, ³JHH = 7.2 Hz, ³JHH = 2.0 Hz, 1 H, Ar-H), 4.00 (t, ³JHH = 6.5 Hz, 2H, O-CH2-), 3.10 [sep, ³JHH = 6.7 Hz, 1 H, CH(CH₃)2], 1.87-1.72 (m, 2H, -CH2-), 1.53-1.41 (m, 2H, -CH2-), 1.40-1.29 (m, 4H, - CH2-, overlapped with the next peak), 1.40-1.29 [d, ³JHH = 6.8 Hz, 6H, CH(CH₃)₂], 0.90 (t, ³JHH = 6.9 Hz, 3H, CH₃) ppm. ¹³C{¹H} NMR (CDCb, 101 MHz): 5 156.8 (Ar- H), 146.1 (br, Ar-H), 129.5 (br, Ar-H), 127.0 (Ar-H), 123.6 (Ar-H), 107.6 (Ar-H), 95.5 (Ar-H), 68.4 (OCH2-), 31.5 (-CH2-), 28.8 (-CH2-), 25.6 (-CH2-), 24.1 [CH(CH₃)], 22.5 (- CH2-), 21.0 [CH(CH₃)], 14.0 (CH₃) ppm. ESI-HRMS (m/z): calcd for C16H24N2O, 260.1889; found, 260.1873.

Synthesis of 6-(hexyloxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridin-1-ium iodide 6-(hexyloxy)-3-isopropylimidazo[1 ,2-a]pyridine (0.172 g, 0.660 mmol) was dissolved in acetonitrile (30 mL) and combined with 2-iodopropane (0.20 mL, 1 .9 mmol) in a 75 mL pressure tube. A polytetrafluoroethylene (PTFE) -coated magnetic stir bar was added and the reaction mixture was heated to 85 °C for 20 h. After cooling to room temperature, the volatiles were removed under reduced pressure by rotary evaporation, yielding an orange coloured residue which was suspended in diethyl ether (40 mL). After sonication/trituration, a pale yellow precipitate was collected by vacuum filtration and washed with diethyl ether (3 x 20 mL) to afford the desired product (0.232 g, 82%).¹H NMR (CDCh, 400 MHz): 5 8.26 (d, ³JHH = 7.6 Hz, 1 H, Ar-H), 8.03-7.96 (m, 1 H, Ar-H), 7.24 (s, br, 1 H, Ar-H), 7.08-7.01 (m, 1 H, Ar-H), 5.70 [sep, ³JHH = 6.6 Hz, 1 H, CH(CH₃)₂], 4.47 (t, ³JHH = 6.1 Hz, 2H, O-CH2-), 3.30 [sep, ³JHH = 7.1 Hz, 1 H, CH(CH₃)₂], 1.89-1.75 (m, 2H, -CH₂-), 1.65-1.24 (m, 6H, - CH₂-, overlapped with CH(CH₃)₂ peaks), 1.58 [d, ³JHH = 6.4 Hz, 6H, CH(CH₃)₂], 1.41 [d, ³JHH = 6.7 Hz, 6H, CH(CH₃)₂], 0.87 (t, ³JHH = 6.3 Hz, 3H, CH₃) ppm. ¹³C{¹H} NMR (CDCh, 101 MHz): 5 163.4 (Ar-H), 141.4 (Ar-H), 132.3 (Ar-H), 126.2 (Ar-H), 114.7 (Ar-H), 112.4 (Ar-H), 92.8 (Ar-H), 72.2 (OCH₂-), 50.1 [CH(CH₃)], 31.5 (-CH₂-), 28.6 (- CH₂-), 25.6 (-CH₂-), 24.0 [CH(CH₃)], 22.5 (-CH₂-), 22.5[CH(CH₃)], 20.7 [CH(CH₃)], 14.0 (CH₃) ppm. ESI-HRMS (m/z): calcd for Ci₉H₃iN₂O⁺, 303.2431 ; found, 303.2418.

Synthesis of 6-(hexyloxy)-1 ,3-diisopropylimidazo[1 ,2-alpyridin-1-ium hydrogen carbonate

6-(hexyloxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridin-1-ium iodide (0.20 g, 0.46 mmol) was dissolved in 5 mL of methanol and added to freshly prepared HCO₃ ^_ resin (5 mL). The pale yellow coloured mixture was stirred for 30 minutes before removing the resin by vacuum filtration. The resin was washed with methanol (3 x 2 mL) before discarding. The methanolic filtrate was dried under a stream of air overnight to afford a pale yellow coloured solid. The solids were treated by sonication/trituration in diethyl ether (2 x 10 mL), removing the yellow coloured supernatant each time before drying in vacuo to give the desired product as a white powder (0.126 g, 74 %). ¹H NMR (CD₃OD, 500 MHz): 5 8.57 (d, ³JHH = 7.5 Hz, 1 H, Ar-H), 7.85 (s, 1 H, Ar-H), 7.43-7.41 (m, 1 H, Ar-H), 7.18-7.14 (m, 1 H, Ar-H), 4.99 [sep, ³JHH = 6.6 Hz, 1 H, CH(CH₃)₂], 4.28 (t, ³JHH = 6.4 Hz, 2H, O-CH₂-), 3.37 [sep, ³JHH = 6.9 Hz, 1 H, CH(CH₃)₂], 1 .95-1.88 (m, 2H, -CH₂-), 1.60 [d, ³JHH = 6.6 Hz, 6H, CH(CH3)₂], 1 .59-1 .52 [m, 2H, -CH₂-, partially overlapped with the CH(CH₃)₂ peak], 1 .44 [d, 3J_HH = 6.9 Hz, 6H, CH(CH₃)₂], 1 .43-1 .38 [m, 4H, -CH₂-, partially overlapped with the CH(CH₃)₂ peak], 0.96 (t, ³JHH = 6.8 Hz, 3H, CH₃) ppm. Note: Due to its rapid exchange with the deuterated solvent, the HCO₃ proton was not observed in the NMR. ¹³C{¹H} NMR (CD₃OD, 126 MHz): 5 165.6 (Ar-H), 162.4 (HCO₃), 143.5 (Ar-H), 135.3 (Ar-H), 129.8 (Ar-H), 1 17.7 (Ar-H), 113.4 (Ar-H), 92.4 (Ar-H), 72.3 (OCH₂-), 51.5 [CH(CH₃)], 33.6 (-CH₂-), 30.8 (-CH₂-), 27.7 (-CH₂-), 25.9 [CH(CH₃)], 24.6 (-CH₂- ), 23.0 [CH(CH₃)], 21.9 [CH(CH₃)], 15.3 (CH₃) ppm. in-1-ium

Prepared following the general procedure above using 6-aminopyridin-3-ol

(0.725 g, 6.58 mmol) and 6-bromohexanyl ferrocene (2.30 g, 6.588 mmol). Analytically pure material was obtained after drying in vacuo for 20 h (2.26 g, 90 %). ¹H NMR

(CDCI₃, 400 MHz): 5 8.33 (d, ³JHH = 7.6 Hz, 1 H, Ar-H), 7.97 (s, br, 1 H, Ar-H), 7.23 (s, br, 1 H, Ar-H), 7.1 1-7.01 (m, 1 H, Ar-H), 5.45 [sep, ³JHH = 6.6 Hz, 1 H, CH(CH₃)₂], 4.41

(t, ³JHH = 6.2 Hz, 2H, O-CH₂-), 4.07 (s, 5H, Cp-H), 4.06-4.03 (m, 2H, Cp-H), 4.03-3.98

(m, 2H, Cp-H), 3.31 [sep, ³JHH = 6.8 Hz, 1 H, CH(CH₃)₂], 2.32 (t, ³JHH = 7.8 Hz, 2H, -

CH₂-), 1.89-1.75 (m, 2H, -CH₂-), 1.62-1.44 (m, 4H, -CH₂-, overlapped with the next peak), 1 .58 [d, ³JHH = 6.8 Hz, 6H, CH(CH₃)₂], 1 .43-1 .33 (m, 2H, -CH₂-, overlapped with the next peak), 1.43 [d, ³JHH = 6.8 Hz, 6H, CH(CH₃)₂] ppm. ¹³C{¹H} NMR (CDCb, 101 MHz): 5 163.3 (Ar-H), 160.0 (HCO₃), 141.2 (Ar-H), 132.3 (Ar-H), 126.7 (Ar-H), 114.4 (Ar-H), 111.9 (Ar-H), 91.8 (Ar-H), 89.3 (ipso-C of Cp), 70.8 (OCH₂-), 68.4 (Cp), 68.0 (Cp), 66.9 (Cp), 49.6 [CH(CH₃)], 31.0 (-CH₂-), 29.5 (-CH₂-), 29.3 (-CH₂-), 28.7 (-CH₂- ), 25.8 (-CH₂-), 23.7 [CH(CH₃)], 22.2 [CH(CH₃)], 20.6 [CH(CH₃)] ppm.

in-1-ium carbonate

Prepared following the general procedure above using 6-aminopyridin-3-ol (2.50 g, 22.7 mmol) and Propargyl bromide (1.75 mL, 23.1 mmol). Note: The O- alkylation in the first step was performed at r.t. ¹ H NMR (CD₃OD, 500 MHz): 5 8.64 (d,

³JHH = 7.5 Hz, 1 H, Ar-H), 7.90 (s, 1 H, Ar-H), 7.55-7.51 (s, br, 1 H, Ar-H), 7.25-7.20 (m, 1 H, Ar-H), 5.10 [s, 1 H, -OCH₂], 4.99 [sep, ³JHH = 6.5 Hz, 1 H, CH(CH₃)₂], 3.39 [sep,

³JHH = 6.7 Hz, 1 H, CH(CH₃)₂], 1 .63 [d, ³JHH = 6.5 Hz, 6H, CH(CH₃)₂], 1 .45 [d, ³JHH = 6.7 Hz, 6H, CH(CHS)₂] ppm. Note: Due to its rapid exchange with the deuterated solvent, the — C =CH proton was not observed in the NMR. ¹³C{¹H} NMR (CD3OD, 126 MHz): 5 163.9 (Ar-H), 162.4 (HCO3), 143.1 (Ar-H), 135.4 (Ar-H), 130.2 (Ar-H), 118.2 (Ar-H), 113.1 (Ar-H), 93.7 (Ar-H), 79.8 (-C = CH), 78.1 ( -C =CH), 59.4 (OCH2-), 51.9 [CH(CH₃)], 25.9 [CH(CH₃)], 23.0 [CH(CH₃)], 21.9 [CH(CH₃)] ppm.

Synthesis of 2-bromo-3-phenylpropanal

2-bromo-3-phenylpropanal was prepared following a modified literature procedure¹ and used without isolation. A 250 mL round bottom flask was equipped with a PTFE-coated stir bar and 50 mL of CH2CI2. Using an ice-water bath, the solvent was cooled to 0 °C before adding N-bromosuccinimide (7.00 g, 39.3 mmol) and L-proline (1.039 g, 9.024 mmol). The round bottom flask was sealed with a septum and placed under an argon atmosphere. The red orange coloured mixture was left to stir at 0 °C for 10 minutes before adding 3-phenylpropanal (4.0 mL, 30 mmol) dropwise to the reaction mixture. The reaction mixture was left to warm to room temperature and was stirred under an argon atmosphere for 2 h. During this time, the colour of the reaction changed from red orange to pale yellow. The reaction mixture was then concentrated to ca. 20 mL by rotary evaporation before adding 100 mL of hexanes to precipitate succinimide, L-proline and other impurities. The precipitates were removed by filtration through a 2.5 cm silica gel plug, washing with hexanes (3 x 50 mL). The colourless filtrate was then concentrated by rotary evaporation while maintaining the bath temperature below 40 °C, to afford the desired product as a pale yellow coloured oil (5.213 g, 81 %). ¹H NMR (CDCh, 400 MHz): 5 9.51 (s, 1 H, HCO), 7.40-7.21 (5H, Ph), 4.48 (ap t, 1 H, CHBr), 3.51 (dd, ³JHH = 14.5 Hz, ³JHH = 6.8 HZ, 1 H, CH2), 3.20 (dd, ³JHH = 14.5 Hz, ³JHH = 6.8 Hz, 1 H, CH2) ppm. ¹³C{¹H} NMR (CDCh, 101 MHz): 5 191.8 (HCO), 136.2 (/pso-Ph), 129.2 (o-Ph), 128.7 (m-Ph), 127.3 (p-Ph), 54.7 (CHBr), 37.9 (CH2) ppm.

2-alpyridin-1-ium bromide

Crude 2-bromo-3-phenylpropanal (4.895 g, 22.97 mmol) as prepared above was immediately dissolved in 50 mL anhydrous ethanol and combined with 2- aminopyridine (1.80 g, 19.1 mmol). A condenser was added, and the yellow coloured solution was heated to 80 °C for 24 h while open to air. After cooling to room temperature, the volatiles were removed by rotary evaporation. The resulting pale yellow coloured solid was suspended in 100 mL of diethyl ether and triturated to afford a white precipitate. The precipitate was isolated by vacuum filtration, washing with diethyl ether (3 x 25 mL) to afford the desired product (5.236 g, 94%). ¹H NMR (CDCb, 400 MHz): 5 8.33 (d, ³JHH = 9.0 Hz, 1 H, Ar-H), 8.25 (d, ³JHH = 6.9 Hz, 1 H, Ar- H), 7.81-7.76 (m, 1 H, Ar-H), 7.57 (s, br, 1 H, Ar-H), 7.36-7.33 (m, 1 H, Ar-H, partially hidden by Ph peaks), 7.33-7.28 (m, 3H, Ph), 7.24-7.19 (m, 2H, Ph), 4.37 (s, 2H, CH₂Ph) ppm. ¹³C{¹H} NMR (CDCb, 101 MHz): 5 139.9 (Ar-C), 133.3 (ipso-C of Ph), 132.4 (Ar-C), 129.3 (Ph-C), 128.4 (Ph-C), 125.5 (Ph-C), 125.2 (Ar-C), 120.3(Ar-C), 117.3(Ar-C), 113.9(Ar-C), 29.9 (CH₂Ph) ppm.

Synthesis of 3-benzylimidazo[1 ,2-a]pyridine

3-benzylimidazo[1 ,2-a]pyridin-1-ium bromide (3.0 g, 10 mmol) in CHCb (100 mL) was transferred to a separatory funnel. The yellow coloured organic solution was washed with a saturated aqueous NaHCOs solution (2 x 50 mL), followed by a saturated NaCI solution (50 mL). After separating the aqueous and organic portions and removing the CHCb by rotary evaporation, 3-benzylimidazo[1 ,2-a]pyridine was obtained as an yellow coloured oil and used immediately without further isolation.

Synthesis of 1 ,3-dibenzylimidazo[1 ,2-alpyridin-1-ium bromide 3-benzylimidazo[1 ,2-a]pyridine (2.160 g, 10.37 mmol) was dissolved in acetonitrile (50 mL) and combined with bromobenzene (3.70 mL, 31 .1 mmol) in a 75 mL pressure tube. A PTFE-coated magnetic stir bar was added before heating to 85 °C for 20 h. After cooling to room temperature, the volatiles were removed by rotary evaporation, yielding a yellow coloured residue which was suspended in diethyl ether (50 mL). After sonication/trituration, the precipitate was collected by vacuum filtration and washed with diethyl ether (3 x 20 mL) to afford the product as a pale yellow coloured powder (3.60 g, 91 %). ¹H NMR (CDsOD, 400 MHz): 5 8.64 (d, ³JHH = 6.9 HZ, 1 H, Ar-H), 8.18-8.13 (m, 1 H, Ar-H), 8.07-8.01 (m, 1 H, Ar-H), 7.89 (s, 1 H, Ar-H), 7.56-7.50 (m, 1 H, Ar-H), 7.46-7.30 (m, 10H, Ph), 5.69 (s, 2H, CH₂Ph), 4.45 (s, 2H, CH₂Ph) ppm. ¹³C{¹H} NMR (CD3OD, 101 MHz): 5 141.1 (Ar-C), 135.8 (ipso-C of Ph), 135.4 (ipso-C of Ph), 135.0 (Ar-C), 130.4 (Ph-C), 130.3 (Ph-C), 130.1 (Ph-C), 129.8 (Ph-C), 129.0 (Ph-C), 128.7 (Ph-C), 128.5 (Ar-C), 128.3 (Ar-C), 124.5 (Ar-C), 118.6 (Ar-C), 112.4 (Ar-C), 51.9 (CH₂Ph), 30.2 (CH₂Ph) ppm.

2-alpyridin-1-ium hydrogen carbonate 1 ,3-dibenzylimidazo[1 ,2-a]pyridin-1 -ium bromide (0.50 g, 1 .3 mmol) was dissolved in 5 mL of methanol and added to freshly prepared HCOs- resin (6 mL). The pale yellow coloured mixture was stirred for 45 minutes before removing the resin by vacuum filtration. The resin was washed with methanol (3 x 2 mL) before discarding. The methanolic filtrate was dried under a stream of air overnight to afford a pale yellow coloured solid. The solids were treated by sonication/trituration in diethyl ether (2 x 10 mL), removing the yellow coloured supernatant each time before drying in vacuo to give the desired product as a white powder (0.330 g, 69 %). ¹H NMR (CD₃OD, 400 MHz): 5 8.60 (d, ³JHH = 6.9 Hz, 1 H, Ar-H), 8.16-8.07 (m, 1 H, Ar- H), 8.07-7.95 (m, 1 H, Ar-H), 7.85 (s, 1 H, Ar-H), 7.54-7.46 (m, 1 H, Ar-H), 7.46-7.25 (m, 10H, Ph), 5.65 (s, 2H, CH₂Ph), 4.42 (s, 2H, CH₂Ph) ppm. ¹³C{¹H} NMR (CD3OD, 101 MHz): 5 161.5 (HCO3), 141.1 (Ar-C), 135.8 (ipso-C of Ph), 135.4 (ipso-C of Ph), 135.0 (Ar-C), 130.4 (Ph-C), 130.3 (Ph-C), 130.1 (Ph-C), 129.8 (Ph-C), 129.0 (Ph-C), 128.7 (Ph-C), 128.5 (Ar-C), 128.3 (Ar-C), 124.5 (Ar-C), 118.6 (Ar-C), 112.4 (Ar-C), 51.9 (CH₂Ph), 30.2 (CH₂Ph) ppm.

Example 2. Electrode and SAM preparation

Organic contaminants on gold electrodes were removed by immersion in “piranha solution” (H₂SO4:H₂O₂ = 3:1 v/v) for 30 seconds and washed with Milli-Q (MQ) water. Electrodes were manually polished in a figure-eight motion to smooth out the gold surface using 0.03 and 0.5 pM alumina powder on a dampened spec- cloth. Alumina powder residue were removed from the gold electrodes by ultrasonicating in MQ water, absolute ethanol and again with MQ water. Each ultrasonication was done for 10 mins. The electrodes were further electrochemically cleaned to remove any absorbed species during the polishing procedure. Preprogrammed cyclic voltammetry (CV) was used to clean the electrodes in base (0.5 M NaOH(aq)) and acid (0.5 M H₂SO4(aq)). For base cleaning, 100 CV cycles between 0 V and 2 V at a scan rate of 0.5 V s^-1. For acid cleaning, 100 CV cycles between 0 V and 1.5 V at a scan rate of 0.5 V s ^-1. CV of the cleaned electrodes were immersed in 5 mM/5 mM Fe(CN)6³'^/4' and 1 M NaCIO4 in MQ water solution. The peak separation was approximately between 65-75 mV to ensure blank surface. The electrodes were rinsed with MQ water and dried under a stream of dry Ar before surface modification.

A freshly cleaned gold working electrode was modified by immersion of 10 mM solution of MIC^iPr»H2CO3 in HPLC-grade MeOH for 24 h at 50 °C. The modified electrode was rinsed with MQ water and dried under a stream of Ar before electrochemical measurement.

Gold chip cleaning and SAM preparation

Gold chips were electrochemically cleaned in 0.5 M H2SO4 by running 100 CV cycles between 0 V and 1 .6 V at a scan rate of 0.4 V s ^-1. This procedure was repeated at least two times or until the cycles stabilized. The gold chips were rinsed with MQ water and dried under a stream of Ar before surface modification, using preparation similar to electrode functionalization.

Example 3. Characterization of SAM Cyclic Voltammetry

Characterization studies included cyclic voltammetry (CV) of an MIC^iPr on Au electrode indicated that the SAM was completely stable over repeated cycling up to 150 cycles between - 0.1 and 0.6 V. Cyclic voltammogram of MIC^iPr showed SAM stability in the range of -0.4 ~ 0.9 V. Outside of that range, the monolayer started to strip off from the surface and there was complete removal at the range between -0.6 ~ 1.1 V.

Electrochemical stability

Electrochemical stability studies of MIC^iPr and NHC^iPr were conducted using cathodic and an anodic chronoamperometry stripping experiment. CV of MIC^iPr I NHC^iPr on gold electrode was measured in 5 mM/5 mM Fe(CN)6^3-/4' as the redox couple and 1 M NaCIO4 as supporting electrolyte in MQ water solution. The electrode was then immersed 1 M NaCIO4 MQ water solution and chronoamperometry (CA) was performed for 30 seconds at a series of applied potential (from -0.5 to -1 .2 V or 0.5 to 1 .2 V). The electrode was then put back into the initial electrolyte solution and CV was measured. Some MICs still remained on surface even after -1 .2 V exposure while NHCs were completely stripped away at - 0.9 V (Figs. 5A-5F). For anodic stripping experiment, both MICs and NHCs comes off at 1 .2 V.

Thermogravimetric analysis Imidazolium hydrogen carbonate salts are valuable air-stable precursors for generating NHC SAMs in solution and ultra-high vacuum (UHV).⁵’ ⁶’ ¹³’ ¹⁷’ ²⁵’ ²⁷ Therefore, it was expected that MIC^iPr»H2CO3 would be similarly effective for producing MIC SAMs, however, initial attempts to prepare films by vapor phase deposition of MIC^iPr»H2CO3 using techniques developed for NHC^iPr proved unsuccessful.

To investigate reasons for this lack of success, thermogravimetric analysis (TGA) of MIC^iPr»H2CO3 was conducted. It revealed that CO2 and H2O were liberated around 160 °C, a higher temperature than NHC^iPr»H2CO3, which cleanly generates NHC^iPr between 100-120 °C. This higher activation temperature is presumably required due to the higher pKa of the MIC precursor. Beyond 160 °C, volatilization of MIC^iPr»H2CO3 Occured but it was slower than NHC^iPr»H2CO3 and has a temperature profile that suggested decomposition accompanies this process (see Fig. 4).

Stability Tests of MIC^iPr and NHC^iPr on gold

SAMs of MIC^iPr on Au were subjected to a variety of conditions including pH extremes (pH 2 and pH 12), refluxing water, and 1 % hydrogen peroxide for 24 hours. During these treatments, the MIC^iPr SAM showed minimal changes to the overall monolayer, as illustrated by comparing XPS signals in high resolution scans of C (1s), O (1 s) and N (1s) and by ToF-SIMS data.

MIC^iPr survived in all conditions, although 1 % H2O2 is the most harsh out of all conditions. In comparison to NHC^iPr long term stability, NHC^iPr seemed to degrade after 5 days in pH 12, while MIC^iPr did not, see Table 2, which shows ToF-SIMS data of MIC^iPr and NHC^iPr before and after stability test under pH 12 for 5 days.

Example 4. Co-deposition between MIC^iPr»H2CO3 and CF3-NHC^iPr»H2CO3

Co-deposition experiments were carried out at 50 °C for 48 hours with 10 mM MIC^iPr»H2CO3 and 10 mM CF3-NHC^iPr»H2CO3 methanolic solution on gold. To determine the surface coverage ratio between MIC^iPr and CF3-NHC^iPr, a trifluoromethyl unit was employed as an XPS reporter along with N 1s signals. The average ratio between MIC^iPr and CF3-NHC^iPr was calculated to be 4:1 , respectively (see Table 3). This ratio demonstrated the preferential formation of SAMs from MIC^iPr in comparison with CF3-NHC^iPr. In addition, the inclusion of a CF3 substituent had no effect on the binding strength of CF3-NHC^iPr. Simple replacement tests between NHC^iPr and CF3-NHC^iPr proved this, with the final monolayer consisting of both NHC^iPr and CF3-NHC^iPr in a roughly 1 :1 ratio. This ratio implied that the binding strengths of NHC^iPr and CF3-NHC^iPr for SAM formation were comparable. When NHC^iPr was exposed to CF3-NHC^iPr»H2CO3 at room temperature for 24 hours, F 1 s atomic concentration percentage increased from 0 to 1 .53%. When CF3- NHC^iPr»H2CO3 was exposed to NHC^iPr at room temperature for 24 hours, F 1 s atomic concentration percentage decreased from 2.74 % to 1 .40 %.

See Table 3, which shows atomic percentage based on XPS data of the codeposition study with MIC^iPr»H2CO3 and CF3-NHC^iPr»H2CO3.

Example 5. MIC on Silver

MIC^iPr»H2CO3 was deposited on silver. Specifically, 150 ~ 200 nm of silver was coated onto a glass prism via evaporation. The surface was then cleaned with acetic acid for 30 minutes and was immediately submerged in a solution of mesoionic carbene in acetonitrile at room temperature and left submerged overnight. See Figs. 6 A-6B, which shows XPS data for the coated silver. The XPS show a small amount of nitrogen contamination in the blank, but an increase was seen in the atomic concentration %. This increase indicates that the carbene was on the surface (top is mesoioinc, bottom is blank).

Example 6. MIC on Copper

Deposition of MIC^iPr»H2CO3 on copper was performed. Specifically, clean copper substrates were prepared by immersing copper chips in glacial acetic acid at 50 °C for 10 minutes. The substrates were then dried under a stream of argon gas. The copper substrates were then exposed to 10 mM DCE (dichloroethane) solutions of the MIC^iPr»H2CO3 for 24 hours at RT. See Figs. 7A-7B, which shows XPS data that confirms that MIC^iPrwas successfully bonded to Cu.

All publications, patents and patent applications mentioned herein are indicative of the level of skill of those skilled in the art to which this invention pertains and are herein incorporated by reference to the same extent as if each individual publication, patent, or patent applications was specifically and individually indicated to be incorporated by reference.

It will be understood by those skilled in the art that this description is made with reference to certain embodiments and that it is possible to make other embodiments employing the principles of the invention which fall within its spirit and scope.

Table 1. Structural Formula, Names of Compounds, and Abbreviated Names

Table 2. ToF-SIMS data of MIC^iPr on gold and NHC^iPr on gold before and after stability test under pH 12 for 5 days

Table 3: Area report of XPS analysis of co-deposition study

Table 4: Replacement experiments between MIC^iPr and CF3*NHC^iPron Au s u rf a ce

Claims

We claim:

1 . A mesoionic carbene precursor of Formula (1 ), or a hydrated form thereof,

where X is a counterion,

Rbackbone is H, a substituted or unsubstituted linear, branched or cyclic aliphatic moiety, a substituted or unsubstituted aromatic moiety, a heteroatom, an ether, an amine, an amide, or any combination thereof; and

Rwingtip is a substituted or unsubstituted linear, branched or cyclic aliphatic moiety, a substituted or unsubstituted aromatic moiety, or any combination thereof, wherein a substituent comprises alkyl, alkenyl, alkynyl, aryl, aryl-halide, heteroaryl, cycloalkyl (non-aromatic ring), Si(alkyl)s, Si(alkoxy)3, halo, alkoxyl, amino, alkylamino, alkenylamino, amide, amidine, hydroxyl, thioether, alkylcarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carbonate, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphate ester, phosphonato, phosphinato, cyano, acylamino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, dith iocarboxyl ate, sulfate, sulfato, sulfonate, sulfamoyl, sulfonamide, nitro, nitrile, azido, heterocyclyl, ether, ester, silicon-containing moieties, thioester, transition metal, or a combination thereof.

2. The mesoionic carbene precursor of claim 1 , wherein Rwingtip is iso-propyl or benzyl.

3. The mesoionic carbene precursor of claim 1 or 2, wherein Rbackbone is H, O- (Ci-Ce-aliphatic), OCH3, CF3, or alkylferrocene.

4. The mesoionic carbene precursor of any one of claims 1 to 3, wherein X is hydrogen carbonate, bicarbonate, carbonate, alkylcarboxylate, arylcarboxylate, carboxylate, halide, tritiate, pseudohalide, cyanide, or azide, where alkyl is an aliphatic moiety and aryl is aromatic.

5. The mesoionic carbene precursor of any one of claims 1 to 4, wherein the compound of Formula (1 ) is:

1 .3-di isopropyl- 1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (MIC^iPr»HI);

1.3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium bromide (MIC^iPr»HBr);

1 .3-di isopropyl- 1 /7-imidazo[1 ,2-a]pyridin-4-ium chloride MIC^iPr»HCI);

1.3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (MIC^iPr»H2CO3);

1 .3-diisopropyl-6-methoxy-1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (^OMeMIC^iPr»HI);

1 ,3-diisopropyl-6-methoxy-1 /7-imidazo[1 ,2-a]pyridin-4-ium bromide (^OMeMIC^iPr»HBr);

1 ,3-diisopropyl-6-methoxy-1 /7-imidazo[1 ,2-a]pyridin-4-ium chloride (^OMeMIC^iPr»HCI);

1 .3-diisopropyl-6-methoxy-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (OMe_M|c^iPr» H2CO3);

1 .3-diisopropyl-6-(trifluoromethyl)-1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (^CF3MIC^iPr,HI);

1 ,3-diisopropyl-6-(trifluoromethyl)-1 /7-imidazo[1 ,2-a]pyridin-4-ium bromide (^CF3MIC^iPr,HBr);

1 ,3-diisopropyl-6-(trifluoromethyl)-1 /7-imidazo[1 ,2-a]pyridin-4-ium chloride (^CF3MIC^iPr*HCI);

1 .3-diisopropyl-6-(trifluoromethyl)-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (^CF3MIC^iPr»H2CO3);

1.3-dibenzyl-1 H-imidazo[1 ,2-a]pyridin-4-ium iodide (M

1 .3-dibenzyl-1 H-imidazo[1 ,2-a]pyridin-4-ium bromide

1 .3-dibenzyl-1 H-imidazo[1 ,2-a]pyridin-4-ium chloride

1.3-dibenzyl-1 H-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (MIC^Bz»H2CO3);

6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide (^OHexMIC^iPr»HI);

6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium bromide (^OHexMIC^iPr*HBr);

6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium chloride (^OHexMIC^iPr*HCI);

6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (OHe^xM|C^iPr»H2CO₃); 6-((6-Ferrocenohexyl)oxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridin-1-ium

(OHexFc_M |C^iPr»H I);

6-((6-Ferrocenohexyl)oxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridin-1-ium (OHexFc_M|C^iPr»HBr);

6-((6-Ferrocenohexyl)oxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridin-1-ium

(^OHexFcMIC^iPr*HCI);

6-((6-Ferrocenohexyl)oxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridin-1-ium (^OHexFcMIC^iPr«H2CO₃);

1 ,3-diisopropyl-6-(prop-2-yn-1 -yloxy)-1 /7-imidazo[1 ,2-a]pyridin-4-ium bromide (OPropargyl_M |QiPr.|_| _Br)_;

1 ,3-diisopropyl-6-(prop-2-yn-1 -yloxy)-1 /7-imidazo[1 ,2-a]pyridin-4-ium chloride (OPropargyl_M |_CiPr.|_|_C|)_;

1 ,3-diisopropyl-6-(prop-2-yn-1 -yloxy)-1 /7-imidazo[1 ,2-a]pyridin-4-ium iodide

(OPropargyi|\/| ICiPr»H I); or

1 ,3-diisopropyl-6-(prop-2-yn-1 -yloxy)-1 /7-imidazo[1 ,2-a]pyridin-4-ium hydrogen carbonate (^OPr°P^ar9y^|M IC^{i Pr}«H2CO3).

6. A method for forming a self-assembled monolayer or overlayer that comprises a mesoionic carbene of Formula (2) on a surface of a substrate,

where Rbackbone is H, a substituted or unsubstituted linear, branched or cyclic aliphatic moiety, a substituted or unsubstituted aromatic moiety, a heteroatom, an ether, an amine, an amide, or any combination thereof; and

Rwingtip is a substituted or unsubstituted linear, branched or cyclic aliphatic moiety, a substituted or unsubstituted aromatic moiety, or any combination thereof, wherein a substituent comprises alkyl, alkenyl, alkynyl, aryl, aryl-halide, heteroaryl, cycloalkyl (non-aromatic ring), Si(alkyl)3, Si(alkoxy)3, halo, alkoxyl, amino, alkylamino, alkenylamino, amide, amidine, hydroxyl, thioether, alkylcarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carbonate, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphate ester, phosphonato, phosphinato, cyano, acylamino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, dith iocarboxyl ate, sulfate, sulfato, sulfonate, sulfamoyl, sulfonamide, nitro, nitrile, azido, heterocyclyl, ether, ester, silicon-containing moieties, thioester, transition metal, or a combination thereof.

7. The method of claim 6, wherein the surface of the substrate is at least partially chemisorbed to the mesoionic carbene.

8. The method of claim 6 or 7, wherein the surface comprises carbon,, mica, alumina, silica, titania, silicon, glass, indium tin oxide, Fe, Rh, Ru, Ir, Ni, Pd, Pt, Cu, Cr, Ag, Au, W, Mo, Co, an alloy, steel, brass, bronze, tungsten carbide, calcium carbide, or any combination thereof.

9. The method of any one of claim 6 to 8, wherein depositing the self-assembled monoloayer provides: surface functionalization; protecting a surface of the substrate; protecting a metal surface; activating a surface for chemical derivatization; activating a metal surface for chemical derivatization; activating a metal surface for catalysis; changing a surface property of a surface.

10. Use of the mesoionic carbene of any one of claims 1 to 5, for detecting, sensing, molecular electronics, biosensors, surface patterning, priming metal surfaces, protecting metal surfaces, protecting metals in microelectronic devices, drug delivery, or sensing applications.

11 . The method of any one of claims 6 to 9, wherein the mesoionic carbene precursor is a carbenic salt that comprises an anion selected from the group consisting of hydrogen carbonate, bicarbonate, carbonate, carboxylate, alkylcarboxylate, arylcarboxylate, carboxylate, halide, triflate, pseudohalide, cyanide, and azide, where alkyl is an aliphatic moiety and aryl is aromatic, wherein the carbenic salt is optionally in a hydrated form.

12. The method of any one of claims 6-9 and 11 , wherein the compound of Formula (2) is the compound of Formula (1) of claim 1 without X.

13. The method of any one of claims 6-9 and 11 , wherein the compound of Formula (2) is:

1 .3-diisopropylimidazo[1 ,2-a]py ridine (MIC^iPr);

1 .3-diisopropyl-6-methoxyimidazo[1 ,2-a]pyridine (^OMeMIC^iPr);

1 .3-diisopropyl-6-trifluoromethylimidazo[1 ,2-a]pyridine (^CF3MIC^iPr);

1 .3-dibenzylimidazo[1 ,2-a]py ridi ne (MIC^Bz);

6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]py ridine (^OHexMIC

6-((6-Ferrocenohexyl)oxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridine

1.3-diisopropyl-6-(prop-2-yn-1-yloxy)-1 /7-imidazo[1 ,2-a]pyridine

14. A mesoionic carbene of Formula (2) of claim 6.

15. The mesoionic carbene of claim 14, wherein the mesoionic carbene is:

1 .3-diisopropylimidazo[1 ,2-a]py ridine (MIC^iPr);

1 .3-diisopropyl-6-methoxyimidazo[1 ,2-a]pyridine (^OMeMIC^iPr);

1 .3-diisopropyl-6-trifluoromethylimidazo[1 ,2-a]pyridine (^CF3MIC^iPr);

1 .3-dibenzylimidazo[1 ,2-a]py ridi ne (MIC^Bz);

6-(hexyloxy)-1 ,3-diisopropyl-1 /7-imidazo[1 ,2-a]py ridine (^OHexMIC

6-((6-Ferrocenohexyl)oxy)-1 ,3-diisopropylimidazo[1 ,2-a]pyridine

1.3-diisopropyl-6-(prop-2-yn-1-yloxy)-1 /7-imidazo[1 ,2-a]pyridine