1. Introduction

The preparation of molecules with broad appeal in the pharmaceutical, chemical and forensics communities having a ketone moiety is a field of widening interest. For example, certain indanone derivatives are precursors to pharmaceuticals which have anticoagulant properties and industrial products such as near infrared dyes. In addition, the 1,2-indanedione family of compounds are used in the forensic sciences to aid in latent fingerprint elaboration.[1-8]

Since fluorine is known to alter bioactivity and other physico-chemical properties in many classes of compounds [6-8], the preparation of new fluorinated examples of these molecules is desirable. Additionally, new insights may be obtained from structure-activity relationship studies and upon determining their bioactivity or efficacy relative to known cases.

The preparation and unique keto-enol properties of fluorinated and trifluoromethylated β-diketones have been thoroughly investigated.[9-12] However, the synthesis and study of cyclic 1,3-diketones possessing the trifluoroacetyl group is relatively limited, especially as it relates to the formation of hydrated species.[11-18] Furthermore, while Selectfluor^® has found wide application in the preparation of selectively fluorinated molecules[19-21], this work reveals several instances where the usual fluorination conditions fail to produce mono-fluorinated ketone products, lead to more than one fluorinated species or result in difluorination.

The desired molecules of interest in this study, which include alicyclic and fused-ring aromatic ketones, are shown in Figure 1. This paper addresses the design and synthetic approach to prepare these fluorinated ketones, interesting hydration properties of these groups as well as the limitations of reactivity and selectivity observed for the Selectfluor^® reagent in this series of ketones.

Figure 1. Target molecules of interest

2. Results and Discussion

2.1. General Synthesis Results

Scheme 1 shows the results of our synthesis efforts. Compounds 1a-7a are commercially available and were used without further purification. Compounds 1b and 2b were synthesized in low to moderate yields using a modified Claisen condensation[11,12].

Compounds 1c, 1d, 2c, 2d, 5b, 6c, and 7b were prepared by direct fluorination with Selectfluor^® in yields ranging from 10-77%. Attempts to obtain the fluorinated compounds 3b, 4b and 6b were unsuccessful.

Scheme 1. Fluorinated ketone synthesis

2.2. Trifluoracetylation Results

While the trifluoroacetylation of 1a and 2a provided 1b and 2b in relatively low yields, some interesting results were nonetheless obtained. During the reactions, samples of the reaction mixture were removed at various intervals, neutralized and the reaction progress monitored by ¹⁹F NMR. The appearance of fluorine resonances noted ca. δ= -75.7 ppm and -76.3 ppm was consistent with the formation of the keto-enol forms of 1b and 2b, respectively.[22] See Figure 2.

Figure 2. Proton NMR for 1b hydrate tautomers

Following the acidic workup and isolation of these products, we found that rapid and quantitative hydration of both the exocyclic keto-enol 1b and endocyclic keto-enol 2b occurred unless the products were kept in moisture-free environments. Possible equilibria for these tautomeric hydrates are shown in Scheme 2.

Scheme 2. Keto-enol hydration product equilibria of 1b and 2b

The equilibria exhibited by these compounds were examined by ¹⁹F and ¹H NMR spectroscopy. Previous work by Salman et al and Ebraheem et al, showed that 2-trifluoroacetylcyclopentanone derviatives preferred an exocyclic keto-enol structures; this was our observation likewise for compound 1b.[14,16,22] Furthermore, chemical shifts to higher frequencies were noted in the ¹⁹F NMR spectra for the CF₃ groups of 1b and 2b following workup of ~ 6 ppm (1b: -82.2 ppm and 2b: -82.9 ppm) indicating hydration similar to that found previously by Ebraheem.[15] In the proton NMR spectra, observation of the H_a singlet ca. 5.1-5.6 ppm indicates the presence of the diketo hydrate and a broad, singlet absorbance for H_b ca. 9.0-9.9 ppm corresponds to overlapping protons of the diketo and keto-enol hydrate tautomers. See Figure 2.

When the H_b signal is normalized to five protons (corresponding to all overlapping hydrate and enol proton signals), the integrated value of the H_a signals permits us to calculate K_eq for the diketo hydrate keto-enol hydrate equilibrium. For both 1b and 2b, the diketo hydrate is the dominant form. See Table 1.

Table 1. Hydrate Species Equilibrium Constant, Keq

2.3. Fluorination Results and Efficacy Testing

Standard fluorination conditions employing the Selectfluor^® reagent ranged from those conducted at room temperature to reflux with reaction times varying from 10 to 96 h, with acetonitrile serving as the solvent. Reaction progress was monitored by 1H and 19F NMR. To test the efficacy of Selectfluor^® as a monofluorination reagent, compounds 1a-7a were subjected to fluorination under a variety of conditions. The results are compiled in Table 2.

Table 2. Fluorination Product Yields Under Differing Reaction Conditions

The cyclic 1,3-diketones 1a and 2a were reactive toward Selectfluor^®, giving the monofluorinated products 1c and 2c in 50% and 55% yields, respectively. The detection of resonances in the ¹⁹F NMR atδ_F(1c)= -161.4 ppm and -195.5 ppm as well as atδ_F(2c)= -167.7 ppm confirmed successful α-fluorination. See Figure 3.

Figure 3. 19F NMR for 1c tautomers

An interesting finding concerns the observation that while both the keto-enolic and diketonic tautomers were observed for 1c, compound 2c exhibited only the keto-enol form. The structures are depicted in Figure 4. In the case of 2c, we surmise that the predominance of the keto-enolic monofluorinated product observed here is likely due to the stability of the enol form of 2-fluoro-1,3-cyclohexanedione, previously proposed by Whangbo and Bumgardner.[23] A detailed ab initio study of the keto-enol diketo equilibrium for a series of cyclic 2-fluoro-1,3-diketones is underway and will be published separately.

Small quantities of α,α-difluorinated products were also obtained from the fluorinations of 1a and 2a. Detection of a single resonance in the ¹⁹F NMR atδ_F= -123.4 ppm and a lone signal in the ¹H NMR at δ_H=2.01 ppm corresponding to the four equivalent α-hydrogens is indicative of 2,2-difluoro-1,3-cyclopentanedione (1d). In accord with previously reported spectral data, 2,2-difluoro-1,3-cyclohexanedione (2d) was confirmed by a resonance in the¹⁹F NMR at δ_F(2d) = -119.1 ppm.[24-26] See Figure 4.

Figure 4. Fluorination products of 1a and 2a and equilibria exhibited by 1c, 1d, 2c and 2d

Consistent with previous work, the α,α-difluoro compounds 1d and 2d underwent hydration when exposed to moisture to give the monohydrates depicted in Figure 4. The hydrate of 1d shows a resonance in the ¹⁹F NMR at_F= -132.7 ppm and a pair of triplet signals in the ¹H NMR at δ_H=2.05 and 2.45 ppm corresponding to the four non-equivalent α-hydrogens on the cyclopentanone ring. The spectroscopic and physical constant data are consistent with literature values for the hydrate of 1d.[24] In a fashion similar to that of 1d, the hydration of 2d was also observed as evidenced by a resonance in the ¹⁹F NMR atδ_F(2d-hydrate) = -128.1 ppm. This phenomenon was reported by Chambers and coworkers, who found that hydration occurred during the preparation of 2,2-difluoro-1,3-cyclohexanedione with dilute fluorine gas in formic acid.[25,26] We found that hydration was reversed when the samples were subjected to high temperatures under vacuum.

Indanone derivatives 3a and 4a were found to be unreactive toward Selectfluor^® under the reaction conditions examined. This is likely due a combination of steric crowding at the site of fluorination via the bulky Selectfluor^® reagent, and the stability of the keto-enol structure shown in Figure 5, which is the major tautomer present for these species in acetonitrile solution. The proton NMR spectra of 3a and 4a acquired in d₃-acetonitrile show singlet signals corresponding to H_b atδ_H ~ 3.9 ppm present in only 5% proportion, supporting assignment of the keto-enol tautomer in solution.

Even though the fluorinations of 3a and 4a were unsuccessful, an interesting side reaction was noted for 3a. During fluorination under refluxing conditions, 3a was deacetylated, and fluorines were substituted resulting in compound 5c in about 40% yield. At present, it is unclear how this transformation occurs, but in earlier work, we noted an analogous deacetylation in the Claisen condensation of 2-acetyl-1-tetralone.[19]

Figure 5. Keto-enol - triketone tautomeric equilibria of 3a and 4a

In contrast, 1,3-indanedione, 5a, was fluorinated with Selectfluor^® to give 5b in good yield over the range of reaction conditions investigated. Studies of the keto-enol tautomeric equilibrium exhibited by 1,3-indandione reveal that it exists in the diketo form in both nonpolar and polar, aprotic solvents. The reaction stops cleanly with monofluorination, but earlier work by our group demonstrated that 5b can be fluorinated to give 2,2-difluoro-1,3-indanedione.[19]

The fluorination of 6a with Selectfluor^® yielded unexpected results. Although we anticipated typical monofluorination adjacent to the C-2 carbonyl group, only the αα-difluorinated product, 6c, was obtained in appreciable yield. The proton NMR for 6c features a multiplet centered at δ_H = 8.14 ppm corresponding to the aromatic protons. A ¹⁹F NMR singlet observed at δ_F = -86.1 ppm is consistent with typical R(C=O)CF₂Ar chemical shift values.[27] We are uncertain at this point why no monofluorination occurred under the reaction conditions and yet difluorination occurred at reflux temperature. Unfortunately, attempts to purify 6c via chromatography for analytical verification led to decomposition of the product. We are currently investigating modifications to the reaction conditions and purification methods to address these issues.

Treatment of 7a with Selectfluor^® provided the α-monofluorinated compound 7b in 70% overall yield, but only under refluxing conditions. As expected, fluorination occurred adjacent to the carbonyl group and physical and spectroscopic data obtained for 7b are consistent with literature data.[30] A ¹⁹F NMR doublet centered at δ_F = -180.7 ppm (²J_F-H = 52.5 Hz) and a ¹H NMR doublet centered at δ_H = 5.55 ppm (²J_H-F = 52.5 Hz) confirm monofluorination on the α-carbon.[27] Attempts to fluorinate 7b were unsuccessful.

2.4. Plausible Mechanisms for the Electrophilic Fluorination of Cyclic Diketones via Selectfluor^®

The literature indicates considerable disagreement concerning the mechanism by which fluorination occurs with reagents such as Selectfluor^®. Polar processes where the “F⁺” ion is the electrophile and single electron transfer (SET) processes which include a “F^. ” radical species have been proposed, but mechanistic studies have not established that a single fluorination mechanism operates in all cases.[20]

In the case of the ketone substrates examined in this study, we propose that an enol species initiates the fluorination by having the C=C double bond attack the Selectfluor^®. In cases where the enol is formed readily under the reaction conditions or is the major tautomer in the reaction medium, such as cyclic β-diketones 1a and 2a, the fluorination can occur at room temperature, and difluorination can become a complicating issue. In cases where the keto tautomer predominates and/or enolization is slow (e.g. 7a), the reaction is slow even under refluxing conditions. However, multiple fluorinations are not as likely. Finally, fluorination via Selectfluor^® does not occur in the usual fashion when the keto-enol substrate is very hindered or very stable (eg. triketones 3a and 4a). Mechanisms for both monofluorination (Scheme 3) and difluorination (Scheme 4) that are consistent with these findings are presented below using compounds 7a and 2b, respectively.

Scheme 3. Monofluorination mechanism of 7a

Scheme 4. Difluorination mechanism of 2b

In Scheme 3, the tautomerization of 7a from ketonic to enolic form occurs slowly in the presence of a proton source, most likely the diazoniabicyclo[2.2.2] octane species depicted above. As reactions involving Selectfluor^® in acetonitrile and molecules with enolizable protons proceed, the solution becomes slightly acidic (pH ~5-6), which is sufficient to enable the keto→enol tautomerization. The enol form, which is only present in small quantities under these conditions due to its instability, reacts with the fluorinating agent to give the monofluorinated product 7b.

In Scheme 4, the enolic form of compound 2b is the most stable tautomer in solution. Several groups have reported this preference of 2b based on spectroscopic data and crystal structures of the molecule.[26,29] Whangbo and Bumgardner have offered a frontier molecular orbital rationale for the unusual stability of the enolic form of 2-fluoro-1,3-cyclohexanedione in support of experimental findings.[23] Because difluorination would result in loss of the enol form, the stable enol form reacts very slowly with a second equivalent of Selectfluor^® to give small quantities of the difluorinated product 2c.

While our proposed mechanisms are consistent with the experimental findings, we note that single electron transfer processes could also be operating, especially in the instance of the difluorination-deacetylation observed for 3a or in cases where the keto enol tautomeric equilibrium favors the keto form, eg. 5a and 7a. This may also explain the exceptional behavior of 6a, which underwent difluorination even though there was no evidence of enolization during the reaction.

3. Conclusions

This work, while still in its initial stages, provides new insight into several areas of current interest regarding selective trifluoroacetylations and fluorinations of cyclic ketones. Trifluoroacetylations of cyclic β-diketones occur under the usual Claisen condensation conditions, but yields are lower than for their acyclic counterparts. [9,11] Trifluoroacetyl groups are subject to hydration due to the enhanced electrophilicity of the carbonyl and these compounds must be maintained in a moisture-free environment to avoid this phenomenon. Likewise, carbonyl groups adjacent to α,α-difluorinated carbons display a tendency for rapid hydration.

Our work has also shed light on the effectiveness of the Selectfluor^® reagent in the monofluorination of cyclic ketones, diketones and triketones. Cyclic β-diketones which can tautomerize from the diketo form to a keto-enol form undergo fluorination under mild conditions, but often difluorination can take place as well. When difluorination occurs, hydration at the ketone adjacent to the fluorines frequently takes place. Indanone derivatives such as 3a and 4a are unreactive toward Selectfluor^® due to a combination of steric and electronic factors arising from the large size of the fluorinating agent as well as the exceptional stability of the keto-enol tautomer. Conversely, ketones that do not tautomerize appreciably due to instability of the enol form react with the Selectfluor^® reagent slowly, if at all, and usually do not give difluorinated products. Notable exceptions to this general rule were the successful fluorinations of 5a and 7a. Likewise, the formation of compound 6b is an apparent departure from this general observation. Further studies are needed to address 6b’s anomalous behavior.

Finally, it is possible that either polar or SET fluorination processes may lead to the products in our study. While we were cautious to ensure that reaction vessels were protected from light so as to minimize radical formation, the fact that fluorination was observed in several cases where enolization was not evident could mean that an SET process might be occurring.

4. Experimental

4.1. Chemicals

All chemicals were obtained from the Aldrich Chemical Company, Eastman Kodak, or Fisher Chemical Company. All solvents and starting materials were checked for purity by mass spectrometry or proton NMR prior to use.

4.2. Instrumentation

Melting points were obtained on a Mel-Temp melting point apparatus and are uncorrected. NMR data were collected using an Anasazi-90 spectrometer operating at 90.0MHz for ¹H, 84.7MHz for ¹⁹F and 22.6MHz for ¹³C or a Brüker Avance 300 spectrometer operating at 300.0MHz for ¹H, 288MHz for ¹⁹F and 75.4MHz for ¹³C. Fluorine-19 NMR chemical shifts were referenced to CFCl₃ as an external standard. IR data were collected on a Perkin-Elmer FT-IR spectrometer with resolutions of 1cm^-1.

4.3. General Procedure for the Preparation of TrifluoroacetylatedDiketones[11,12]

To 50 mL diethyl ether in a round bottom flask equipped with a magnetic stirrer is added 60 mmol of sodium methoxide slowly. Then, 1eq (60 mmol) of methyl trifluoroacetate is added dropwise slowly while stirring. After 5 minutes, 1eq (60 mmol) of the ketone is added dropwise and stirred overnight at room temperature under a calcium chloride drying tube. The resulting solution is evaporated to dryness under reduced pressure and the solid residue dissolved in 30 mL 3M sulfuric acid. The acidic solution is extracted with 3-15 mL aliquots of diethyl ether, and the organic layer dried over NaSO4. The solvent is evaporated under reduced pressure, the crude diketone purified by distillation, recrystallization or radial chromatography, and purity confirmed by ¹H, ¹³C, and ¹⁹F NMR spectroscopy, mass spectrometry and literature melting or boiling points.

2-trifluoroacetyl-1,3-cyclopentanedione (1b) This compound was obtained as a 95:5 mixture of exocyclic enol:triketo tautomers as pale yellow crystals (Et₂O) in 40% yield, mp 138-140°C. NMR: ¹H: δ 2.63 (CH₂, 4H, s), 5.41 (keto CH, 1H, s). ¹³C: δ 30.9, 105.1, 107.2, 115.2 (CF₃, q, ¹JC-F =274Hz), 159.5 (C-CF₃, q, ²JC-F=36Hz), 195.3, 205.0. ¹⁹F: δ-75.7. Analysis calcd for C₇H₅F₃O₂: C, 43.32, H, 2.60. Found: C, 43.10, H, 2.52. The 1b-hydrate was obtained as a reddish oil (1.7:1 mixture of diketo hydrate:keto-enol hydrate). NMR: ¹H: δ2.71 (CH₂, 4H, s), 5.58 (CH, 1H, s), 9.88 (OH, 3H, bs). ¹³C: δ 30.9, 105.1, 107.2, 115.2 (CF₃, q, ¹JC-F =274Hz), 195.3, 205.0. ¹⁹F: δ -82.2 (3F, bs).

2-trifluoroacetyl-1,3-cyclohexanedione (2b) This compound was obtained in 20% yield as a beige solid, m.p. 71-74°C. NMR: ¹H: δ 1.98-2.6 (CH₂, 6H, m). ¹³C: δ 21.0, 28.8, 30.9, 106.2, 108.1, 117.2 (CF₃, q, ¹JC-F=271Hz), 162.6 (C-CF₃, q, ²JC-F=37Hz), 196.2, 201.0. ¹⁹F: δ -76.3 (enol). Analysis calcd for C₈H₇F₃O₂: C, 46.16, H, 3.39. Found: C, 46.26, H, 3.31. The 2b-hydrate was obtained as a red-orange oil (1.2:1 mixture of diketo hydrate:keto-enol hydrate.) ¹H: δ 1.98 (CH₂, 2H, m, J=5.55Hz), 2.35 (CH₂, 2H, t, J=6.41Hz), 2.71 (CH₂, 2H, t, J=6.59Hz), 5.49 (hydrate, 1H, s), 9.0 (hydrate and enol, 3H, bs). ¹⁹F: δ-82.9 (3F, bs).

4.4. General Procedure for the Preparation of Fluorinated Diketones

A 100mL round bottom flask equipped with a stir bar is charged with 50mL CH₃CN and Selectfluor^® (0.78 g, 0.0022mol). Once the Selectfluor^® has dissolved, the ketone (1eq, 0.0022mol) is added slowly with stirring. The reaction is capped and allowed to run for 10-96 h at room temperature or under reflux at a temperature of 70°C for 10-96 h. The solvent is removed under reduced pressure. The resulting residue is taken up in ~20mL CH₂Cl₂ and washed with 3 aliquots of ~20 mL distilled water. The organic layers are combined and dried over Na₂SO₄ and the product purified by radial chromatography or recrystallization.

2-fluoro-3-hydroxycyclopent-2-enone and 2-fluoro- 1,3-cyclopentanedione (1c): This compound was obtained as a 52:48 mixture of keto-enol and diketo tautomers in 50% yield as a yellow-brown solid, mp 70-72°C. NMR: ¹H: δ 2.36 (t, ³J_H-H = 16.2 Hz, 2H), 2.85 (m, 2H), 5.91 (d, ²J_H-F = 47.7 Hz, 1H). ¹³C: δ31.1, 90.8 (d, ¹J_C-F = 251.3 Hz), 122.3 (d, ¹J_C-F = 233.9 Hz), 210.1 (d, ²J_C-F = 31.0 Hz). ¹⁹F: keto-enol: δ-161.4 (s, 1F); diketo: δ-195.5 (d, ²J_F-H = 47.7 Hz, 1F). Analysis calcd for C₅H₅FO₂: C, 51.73, H, 4.34. Found: C, 51.48, H, 4.31.

2,2-difluoro-1,3-cyclopentanedione (1d): This compound was obtained in 15% yield as tan crystals, mp 41-43°C. NMR: ¹H: δ 2.21 (H₂C-C=O, 4H, m). ¹³C: δ 31.1, 110.8 (t, ¹J_C-F = 248.3 Hz), 199.3 (t, ²J_C-F = 28.0 Hz). ¹⁹F: δ-123.4 (s, 2F). Analysis calcd for C₅H₄F₂O₂: C, 44.79, H, 3.01. Found: C, 44.68, H, 3.12.

2,2-difluoro-3,3-dihydroxy-1-cyclopentanone (1d-hydrate): This compound was obtained from the hydration of 1d as beige crystals (ethyl acetate), m.p. 71-74°C [lit. 24] m.p. 70-72°C. NMR: ¹H: δ 2.04 (m, 2H), 2.45 (m, 2H), 6.91 (s, hydrate, 2H). ¹³C: δ 31.0, 32.1, 94.6 (t, ²J_C-F = 20.9 Hz), 112.5 (t, ¹J_C-F = 254.8 Hz), 210.8 (t, ²J_C-F = 18.5 Hz). ¹⁹F: δ -132.7 (s, 2F).

2-fluoro-3-hydroxycyclohex-2-enone (2c): This compound was obtained in 55% yield as pale tan crystals (ethyl acetate), m.p. 150-152°C [lit. 25] (m.p. 152-153°C). NMR: ¹H: δ 1.90-2.50 (m, 6H), 11.4 (bs, 1H). ¹³C: δ20.1, 22.2, 33.0, 106.1, 37.9, 139.8.1 (d, ¹J_C-F = 235.3 Hz), 200.1 (d, ²J_C-F = 14.5 Hz). ¹⁹F: δ-167.7 (s, 1F).

2,2-difluoro-1,3-cyclohexanedione (2d): This compound was obtained in 10% yield as pale tan crystals (ethyl acetate), m.p. 68-70°C [lit. 25] (m.p. 70°C). NMR: ¹H: δ 1.9 (m, 2H), 2.4 (m, 4H). ¹³C: δ 18.0, 37.9, 114.1 (t, ¹J_C-F = 257.6 Hz), 195.2 (t, ²J_C-F = 23.5 Hz). ¹⁹F: δ-119.0 (s, 2F).

2,2-difluoro-3,3-dihydroxy-1-cyclohexanone (2d-hydrate): This compound was obtained from the hydration of 2d as pale tan crystals (ethyl acetate), m.p. 68-76°C [lit. 25] NMR: ¹H: δ 1.85 (m, 2H), 2.11 (m, 2H), 2.49 (m, 4H). ¹³C: δ 20.0, 35.0, 96.0 (t, ¹J_C-F = 257.6 Hz), 114.2 (t, ¹J_C-F = 257.0 Hz), 197.3 (t, ²J_C-F = 24.5 Hz). ¹⁹F: δ -128.1 (s, 2F).

2-fluoro-1,3-indanedione (5b). This compound was obtained in 67% yield as pale yellow crystals (EtOH), m.p. 95–97°C [lit 19] (m.p. 96–98°C). NMR: ¹H: δ 5.4 (d, ²J_H-F = 51.0 Hz, 1H), 7.65–8.22 (m, 4H). ¹³C: δ 90.1 (d, ¹J_C-F = 211.2 Hz), 125.3, 138.9, 141.9, 193.5 (d, ²J_C-F = 24.0 Hz). ¹⁹F: δ −207.3 (d, ²J_F-H = 51.1 Hz, 1F).

2,2-difluoro-1,3-indanedione (5c). This compound was obtained in 77% yield as a yellowish-brown solid (EtOH), m.p. 115–117°C [lit 21] (m.p. 117–118°C). NMR: ¹H: δ 8.0–8.18 (m, 4H). ¹³C: δ 104.1 (t, ¹J_C-F = 264 Hz), 128.6, 138.1, 139.2 (t, ³J_C-F = 4.3 Hz), 185.8 (t, ²J_C-F = 24.1Hz). 19F: δ −125.8 (s, 2F).

3,3-difluoro-1,2-indanedione (6b): This compound was obtained in 25% yield as yellow-brown crystals, m.p. 99-103°C, dec. NMR: ¹H: δ 7.1-8.6 (m, 4H). ¹⁹F: δ-86.1 (s, 2F). Purification by column chromatography resulted in decomposition of the product, so further characterization was not possible at the time of this publication.

(±)1-fluoro-2-indanone (7b) This compound was obtained in 70% yield as a racemic mixture of enantiomers as a brown oil [lit 29]. NMR: ¹H: δ 3.58 (s, 2H), 5.7 (d, ²J_H-F =52.5Hz, 1H), 7.0-7.6 (m, 4H). ¹⁹F: δ-180.8 (d, ²J_F-H =52.5Hz, 1F).

ACKNOWLEDGEMENTS

The authors thank Georgia Gwinnett College SS&T STEC 4500 Research Seed Grant program and the United States Army Research Laboratory (C&LS-2) for the funding of this work.