The ESI-Mass spectra of DPTR-I (Figure 1) shows m/z peak at 324 indicating that the DPTR-I molecular ion species appeared as [M + H]⁺ and for DPTY-I (Figure 2, (Suppl Material, SM)) the mass spectra shows a peak at 301 specifying that the DPTY-I molecular ion species also appeared as [M + H]⁺. The M.ps 130˚C - 133˚C for DPTR-I and 128˚C - 131˚C for DPTY-I.

¹H-NMR spectra of DPTR-I/DPTY-I

DPTR-I (Figure 3): ¹H-NMR (400 MHz, CD₃OH): δ = 10.02 (s, 1H) 7.94 (d, 1H), 7.74 (d, 1H), 7.14 - 7.12 (m, 2H), 6.75 - 6.72 (m, 1H), 6.61 (d, 1H), 6.48 - 6.44 (m, 1H), 6.29 (d, 1H), 6.21 - 6.16 (m, 1H), 6.13 - 6.05 (m, 1H), 2.77 (s, 3H), 2.72 (brs, 1H), 1.65 - 1.62 (m, 2H) [17] [18] .

DPTY-I (Figure 4, SM): ¹H-NMR (400 MHz, DMSO-d6): δ = 9.24 (s, 1H), 8.80 (d, 1H), 8.65 (d, 1H), 7.99 (t, 1H), 7.98 (d, 1H), 7.63 - 7.60 (m, 1H), 7.00 (d, 2H), 6.63 (d, 2H), 4.73 - 4.68 (m, 1H), 3.64 (S, 3H), 3.09 (d, 2H).

The mechanism involves,

1) Proton abstraction occurs from Pa followed by the addition of carboxylate anion (-Coo⁻) to the electron de- ficient carbon atom of HATU. This results in the formation of new C-O bond.

2) The resulting anion reacts with the newly formed activated carboxylic acid derived from intermediate to form an OBt activated ester.

3) The amine reacts with the OBt activated ester to form the amide product.

Similar mechanism was proposed earlier for the formation of amide bond [19] -[21] .

The ESI-Mass spectra of DPTR-II (Figure 5) shows m/z peak at 315 suggesting that the DPTR-II molecular ion species appeared as [M + Li]⁺ and for DPTY-II (Figure 6, SM) the mass spectra shows a peak at 287 indicating that the DPTY-II molecular ion species appeared as [M + H]⁺. The M.ps 131˚C - 134˚C for DPTR-II and 129˚C - 132˚C for DPTY-II.

¹H-NMR spectra of DPTR-II/DPTY-II

DPTR-II (Figure 7): ¹HNMR (400 MHz, DMSO-d₆): δ = 9.88 (s, 1H), 7.67 (d, 1H), 7.19 - 7.08 (m, 3H), 6.69 - 6.66 (m, 1H), 6.58 (d, 1H), 6.37 (d, 1H), 6.19 (d, 1H), 6.09 - 6.05 (m, 1H), 5.93 - 5.89 (m, 1H), 3.40 - 3.38 (m, 1H), 2.37 - 2.32 (m, 2H).

DPTY-II (Figure 8, SM): 1H-NMR (400 MHz, DMSO-d6): δ = 9.22 (s, 1H), 8.65 - 8.60 (m, 2H), 8.01 - 7.98 (m, 2H), 7.62 (d, 1H), 6.99 (d, 2H), 6.22 (d, 2H), 4.67 - 4.62 (m, 1H), 3.08 (d, 2H).

IR spectra of DPTR-II/DPTY-II

The IR spectra for the above intermediates were recorded to confirm the presence of acidic proton (COOH functional group).

DPTR-II (Figure 9): IR υ_max (MeOH): 3323 (CONH), 3098 (COOH), 1625 (C=O), 1516 (C=C) 1437 (C=N), 1245 (C-N) cm⁻¹ [22] .

DPTY-II (Figure 10, SM); IR υ_max (MeOH): 3330 (CONH), 2956 (COOH), 1739 (C=O), 1439 (C=C), 1367 (C=N), 1218 (C-N) cm⁻¹.

The general mechanism for the de-esterification by base involves a series of equilibria. The hydroxide anion adds to the carbonyl group of the ester. The direct products are a carboxylic acid salt and an alcohol. To convert the salt to the corresponding carboxylic acid, acidic workup of the product mixture was performed [23] .

The ESI-Mass spectra of DPPTR-(Figure 11) shows m/z peak at 400 indicating that the DPPTR molecular ion species appeared as [M + H]⁺ and for DPPTY (Figure 12, SM) the mass spectra shows a peak at 377 suggesting that the DPPTY molecular ion species appeared as [M + H]⁺. The M.ps 136˚C - 138˚C for DPPTR and 133˚C - 135˚C for DPPTY.

¹H-NMR spectra of DPPTR/DPPTY

DPPTR (Figure 13); 1H-NMR (400 MHz, DMSO-d6): δ = 10.68 (s, 1H), 9.82 (d, 2H), 8.59 - 8.50 (m, 1H),

8.26 - 8.14 (m, 2H), 7.91 - 7.85 (m, 2H), 7.74 - 7.67 (m, 2H), 7.59 (s, 1H), 7.50 - 7.31 (m, 2H), 7.23 - 7.08 (m, 1H), 7.01 - 6.99 (m, 1H), 4.95 (d, 3H), 4.37 (d, 1H), 2.50 - 2.47 (m, 1H), 2.36 - 2.31 (m, 1H)

DPPTY (Figure 14, SM); 1-HNMR (400 MHz, DMSO-d₆): δ = 8.82 (t, 1H), 8.65 (t, 2H), 8.48 (d, 1H), 8.02 (d, 2H), 7.75 (t, 1H), 7.62 - 7.59 (m, 1H), 7.25 (t, 1H), 7.10 (d, 1H), 7.00 (d, 2H), 6.60 (d, 2H), 4.79 - 4.74 (m, 1H), 4.43 - 4.34 (m, 2H), 3.06 - 2.99 (m, 2H).

IR spectra of DPPTR/DPPTY

DPPTR (Figure 15): IR υ_max (MeOH): 3307 (CONH), 1660 (C=O), 1516 cm⁻¹ (C=C), 1478 (C=N), 1232 (C-N) cm⁻¹.

DPPTY (Figure 16, SM): IR υ_max (MeOH): 3323 (CONH), 1741 (C=O), 1371 (C=C), 1443 (C=N), 1224 (C-N) cm⁻¹.

The mechanism for the formation of final ligands is similar to that described for the formation of DPTR-I/ DPTY-I except that the starting materials are different.

Picolinic acid, Tryptophan-methyl ester, Tyrosine-methyl ester, picolylamine and LiOH∙H₂O are obtained from sigma chemical company (99% purity), USA. HATU and solvents (DIEA, methanol, Ethylacetate, n-Hexane and dimethylformamide) were purchased from Merck, India and were of analar grade. The chemicals were used as supplied. The TLC silica gel plates (60 F₂₅₄) were obtained from Merck. Infrared spectra were recorded on a Perkin-Elmer FT-IR spectrometer in the range of 4000 - 750 cm⁻¹ using Methanol as solvent. ESI mass spectra for the ligands were recorded on a Quattro Lc (Micro mass, Manchester, UK) triple quadruple mass spectrome- ter with Mass Lynx software and Shimadzu, model LC-MS; 8030. The ¹H-NMR spectra were recorded on a Bruker Biospin and Avance-III 400 MHz Fourier Transform Digital NMR Spectrometer, Switzerland using DMSO as solvent and TMS as the internal standard. The melting points were recorded on a cintex melting point instrument and are uncorrected. All reactions were carried under N₂ atmosphere.

The synthesis of peptides involves three steps (Scheme 1). The following procedure was adopted for the synthe- sis.

DPPTR:

For the synthesis of DPPTR, 2-picolinic acid (0.2 g, 1.62 mmol) was dissolved in dry DMF (10 mL) and HATU (0.74 g, 1.95 mmol) and DIEA (0.62 g, 4.86 mmol) were added. The solution was cooled to 0˚C. The solution was stirred for 30 min followed by the addition of Tryptophan-methyl ester (0.62 g, 2.43 mmol). The mixture was warmed to room temperature and the stirring continued for another 12 h. After the workup, the sol- vent was removed under reduced pressure and the remaining solid was washed with petroleum ether to afford the compound, DPTR-I (yield: 0.481 g, 93%). In the second step, the protected methyl ester (OMe) was re- moved by saponification using LiOH in MeOH to get DPTR-II. It was purified by column chromatography (yield: 0.419 g, 91%). Finally, DPTR-II (0.42 g, 1.35 mmol) was dissolved in dry DMF (10 ml) and HATU (0.61 g, 1.62 mmol) and DIEA (0.52 g, 4.05 mmol) were added and the mixture was cooled to 0˚C. The solution was stirred for 30 min and the picolylamine (0.22 g, 2.03 mmol) was added. The mixture was warmed to room temperature and stirred for another 12 h. After the workup, the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate) to afford the compound DPPTR (yield: 0.459 g, 85%). The DPPTY was synthesized as per the procedure described in SM.