Adducts of rhodium(II) tetraacylates with methionine and its derivatives: 1H and 13C nuclear magnetic resonance spectroscopy and chiral recognition

Tetrahedron: Asymmetry 21 (2010) 2346–2355

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Adducts of rhodium(II) tetraacylates with methionine and its derivatives: 1H and 13C nuclear magnetic resonance spectroscopy and chiral recognition Rafał Głaszczka a, Jarosław Jaz´win´ski a,⇑, Bohdan Kamien´ski a,b, Monika Kamin´ska c a

Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland Institute of Physical Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland c The Faculty of Chemistry, University of Warsaw, ul. Pasteura 1, 02-093 Warsaw, Poland b

a r t i c l e

i n f o

Article history: Received 13 July 2010 Accepted 12 August 2010

a b s t r a c t Complexation of rhodium(II) dimeric tetraacylates: tetraacetate Rh2AcO4, tetratrifluoroacetate Rh2TFA4 , and (S)-Mosher’s acid salt Rh2MTPA4 with both enantiomerically pure and racemic methionine and its derivatives: hydrochloric salt of methionine, hydrochloric salt of methionine methyl ester, N-formyl methionine, N-phthaloyl methionine, N-phthaloyl methyl ester of methionine, and methyl ester of N,Ndimethylmethionine has been investigated by means of 1H and 13C nuclear magnetic resonance (1H and 13C NMR) and absorption electronic spectroscopy in the visible range. Complexation processes were investigated in D2O or CDCl3 solutions, depending on the ligands’ and rhodium salts’ solubilities. Some supporting measurements were performed in the solid phase, using 13C and 15N CPMAS NMR techniques. All ligands investigated form 1:1 and 1:2 adducts in the solution, depending on the rhodium salt to ligand molar ratios. The complexation site in the ligands (S atom) was deduced on the basis of the NMR parameter adduct formation shift (Dd = dadduct dligand) and calculated chemical shifts (DFT, NMR GIAO). In the cases of the Rh2TFA4 and Rh2MTPA4 adducts, decreasing the temperature within the range 220–254 K slowed down the ligand exchange and allowed us to observe the signals of all diastereoisomers in the 1H and 13C NMR spectra. Ó 2010 Elsevier Ltd. All rights reserved.

1. Introduction Dimeric rhodium(II) salts are known to form adducts with a large number of organic ligands.1 These adducts as well as dirhodium salts have been widely used in organic chemistry as catalysts;2–4 as auxiliary reagents in the spectroscopy of organic species;5–11 and as building blocks in supramolecular chemistry.12 Furthermore, rhodium(II) dimeric salts have appeared to be active as DNA replication inhibitors, and have been tested as anticancer agents.13 The interaction of dirhodium salts with DNA bases, dinucleotides, and oligonucleotides has been the subject of numerous work; recent examples include published papers concerning experimental studies and theoretical considerations.14–18 The application of rhodium(II) salts in medicine justified the extension of our research to adducts with biological importance, such as peptides or amino acids. A few papers have been devoted to rhodium(II) adducts with amino acids. Rhodium(II) dimeric tetraacylate containing four proline molecules in equatorial positions has been applied as a chiral catalyst.3,4 The absolute configurations of a few a-amino acids

⇑ Corresponding author. Tel.: +48 22 3432014; fax: +48 22 6326681. E-mail addresses: [email protected], [email protected] (J. Jaz´win´ski). 0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetasy.2010.08.010

have been determined by a ‘dirhodium method’, using enantiomerically pure rhodium salts of Mosher’s acid (Rh2MTPA4) as auxiliary reagents.19 It has been mentioned that rhodium tetraacetate formed a 1:2 axial adduct with methionine via the sulfur atom. Cysteine, another amino acid bearing a sulfur function, irreversibly replaced all the l-acetates in the dirhodium salt producing an equatorial adduct.13,20 Our previous works on dirhodium complexes include 1H, 13C, and 15N NMR studies of adducts with amines and heteroaromatic ligands in CDCl3 solution.21–27 Chloroform was the solvent of choice, due to the inability of adduct formation with a rhodium salt. In contrast, solvents such as water, methanol, dimethylsulfoxide or acetonitrile were considered as less convenient because of the formation of their own adducts with metal salts, and competition with the ligands. Nevertheless, these solvents have been applied in special cases.28,29 Herein we report the interaction of dirhodium tetraacylates with methionine and some of their derivatives. Since methionine was not soluble in chloroform, some measurements were performed in a water solution. Water was included in our investigations because of its importance in biological applications. The present work is focused on the application of nuclear magnetic resonance spectroscopy (NMR) to the investigation of the complexation process, and on the exploration of phenomena related to chirality and chiral recognition.

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and depends on the ligand to substrate molar ratio, concentrations, temperature etc. This generally occurred for our measurements taken at room temperature, namely the complexation of Rh2AcO4 in D2O and CDCl3. In contrast, experiments in a slow exchange regime, when the signals of all the species are visible, provide proper adduct chemical shifts and Dd. Such parameters characterize the adduct and remain invariable for a given solvent. This was the case for the Rh2MTPA4 and Rh2TFA4 adducts, which were studied at decreased temperatures. In order to clarify the discussion and in order to avoid mistakes, we denoted the first parameter as Dd and the second as Ddadd. In the text, sample compositions were given as a rhodium salt to ligand molar ratio (see Section 4 for details). The NMR data for the ligands and adducts are shown in Table 1.

2. Results and discussion The following dirhodium salts were used as substrates: tetraacetylate Rh2AcO4, trifluoroteraacetylate Rh2TFA4, and the enantiomerically pure salt of Mosher’s acid [(S)-isomer] Rh2MTPA4 (Fig. 1). Both enantiomers of methionine and its derivatives were applied as ligands. The measurements were performed either in water or in chloroform, depending on the ligand solubility. Experimental and calculated NMR chemical shifts are shown in Table 1 and Figure 3. Complexation conditions depended on the substrate and ligand solubility. If both the substrate and ligand were soluble, the composition of the solutions depended only on the amount of reagents added. These occurred for Rh2AcO4 and Rh2TFA4 in D2O and for Rh2TFA4 and Rh2MTPA4 in CDCl3 solutions. In contrast, Rh2AcO4 was poorly soluble in CDCl3 and practically all of the salt was deposed on the bottom of NMR tube. The salt could only appear in the solution as an adduct. Consequently the solution contained adducts and/or ligand excess and the composition of the solution depended on the equilibrium between the soluble and insoluble materials. The appearance of NMR spectra depended on the ligand exchange rate. Fast ligand exchange (on an NMR timescale) resulted in chemical shift averaging and, sometimes, in signal broadening. These usually occur for NMR measurements performed at room temperature. Consequently, the signals of the individual species in the solution were not observed; quite often the spectra were difficult to interpret. In contrast, slow ligand exchange allowed us to observe the signals of individual adducts in the solution. Slowing down the exchange process was achieved by measurements at a decreased temperature. The complexation process was quantified by a parameter adduct formation shift Dd, defined as a difference between chemical shifts of a signal in an adduct and the corresponding signal in non-complexed (free) ligand (Dd = dadduct dligand, in ppm). It should be noted that this parameter has in practice two slightly different meanings, depending on the NMR data used for the calculation. Under fast exchange conditions the signals appear in averaged positions and the chemical shifts of the adduct are not available; instead, signals derived from the equilibrium mixture of the adduct and free ligand are observed. Consequently, Dd is always equal to or smaller than the Dd of the adduct alone,

2.1. Complexation of 1, 1-HCl and 2-HCl with Rh2AcO4 in D2O Methionine 1, the hydrochloric salt of methionine 1-HCl and the hydrochloric salt of methionine methyl ester 2-HCl were the first ligands we investigated. All of these ligands are soluble in water and insoluble in chloroform, which was the solvent of choice in our previous investigations.21–27 Water forms its own adducts (dihydrates) with dirhodium salts and competes with the ligand. Despite these inconveniences, the complexation occurred in water: the addition of the ligand to a Rh2AcO4 solution caused a color change from blue to red. Titration experiments monitored by electronic absorption spectroscopy in the visible range (vis) (Fig. 2), revealed the formation of at least two species in solution, presumably the 1:1 and 1:2 adducts. At the beginning of the titration, the curves arising from the adduct crossed the Rh2AcO4 absorption line at 588 nm; then band intensities increased and an isosbestic-like point appeared at 571–573 nm, due to the conversion of the 1:1 adduct to the 1:2 adduct. All three ligands behaved similarly. It should be mentioned that in the case of HCl salts, the Cl anion should also be considered as a ligand. Titration experiments (from 1:0.5 to 1:2.5 Rh2AcO4 to ligand molar ratio) were repeated using NMR spectroscopy. Due to the fast ligand exchange, 1H NMR spectra showed one set of signals in averaged positions; that is, there were no signals of individual species (1:1 and 1:2 adducts) in the spectra. The largest Dd was observed for the 1:0.5 sample; only a small decrease in Dd occurred

O

R O

O

Rh O R

O

R

S

O

O

NR2

Rh

O O

O R'

S

O N

O

R'

O

1 R = H, R' = H 2 R = H, R' = CH3 7 R = R' =CH3

O

R

Rh2 AcO4 (R = CH 3) Rh2 TFA 4 (R = CF3) Rh2 MTPA4 (R = CPh(CF3 )(OCH3 ))

4 R' = H 5 R' = CH3 O S

O O

O

NH

Me OH O

NH

H

H

3

6

Figure 1. Dirhodium salts and ligands studied. The arrows mark the axial positions in the dirhodium salts, that are able to bond to organic ligands.

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Figure 2. Absorption electronic spectra (visible range) of Rh2AcO4 adducts in D2O. Titration of Rh2AcO4 by methionine 1 (a), hydrochloride salt of methionine 1-HCl (b), and hydrochloride salt of methionine methyl ester 2-HCl (c). Green curves correspond to Rh2AcO4 solutions; the next curves correspond to samples containing Rh2AcO4 and ligands in the molar ratio from 1:0.25 to 1:2.5 (step 0.25). Rh2AcO4 concentrations (4.3, 8.9, and 6.1 mM solutions in 0.5 cm cell, respectively) were constant during each titration.

Table 1 1 H and 13C NMR data for some methionine derivatives and their adducts with rhodium(II) tetraacylatesa SCH2CH2

SCH2CH2

Ligands, D2O solutions, 303 K 1 2.13(13.9) 1-HCl 2.12(13.9) 2-HCl 2.13(13.9)

SCH3

2.63(28.9) 2.68(28.6) 2.70(28.4)

Ligands, CDCl3 solutions, 303 K 3 2.03(15.5)

2.46(29.8)

4

2.03(15.0)

b

2.54 (26.6) b

CH

C@O

R

2.11/2.19(29.7) 3.85(53.9) 2.18/na(29.0) 4.15(52.2) 2.23/2.31(28.7) 4.31(51.7)

(174.3) (172.2) (170.6)

3.86(53.7) (OCH3)

1.97/2.14(31.7) 4.75(50.2)

(172.0)

b

(172.5)

b

2.34/2.44 (30.1) 5.20(49.8)

5

2.01(15.3)

2.45 (28.0)

2.40/2.50 (30.8) 5.03(50.8)

(169.5)

7

2.03(15.4)

2.47(30.7)

1.86/1.94(28.7) 3.27(66.0)

(172.3)

[0.25/ [0.11( 0.1)] 0.29( 0.8)] [0.25/na( 0.6)] [0.04(0.6)] [na/na( 0.6)] [0.09(0.2)]

[( 0.3)]

Adducts with Rh2AcO4, D2O solution, 303 Kc 1 (1:1) [0.37(1.6)] [0.45(1.7)] 1-HCl (1:1) 2-HCl (1:1)

[0.39(1.7)] [0.31(1.7)]

[0.44(2.0)] [0.35(2.0)]

Adducts with Rh2AcO4, CDCl3 solution, 303 Kc 3 (1:1) [0.44(2.2)] [0.59(2.4)] 4 (1:0.5)

[0.45(1.9)]

[0.47(4.9)]

7 (1:0.5)

[0.38(0.6)]

[0.64(1.8)]

[0.37/0.39(0.6)] [0.06(0.4)] [0.40/ 0.42( 4.0)] [0.79/ 0.93( 0.2)]

Adducts with (4S)-Rh2MTPA4, CDCl3 solution, various temperaturesd 3 (rac) (1:1, 2.43, 2.44 303 K) 3 (S) (1:1, 254 K) 2.47

[1.06(3.5)]

5.12 4.90 4.84

3 (S) (1:2, 254 K) 2.46

4.72

3 (R) (1:2, 254 K) 2.42

4.72

3 (rac) (1:2, 254 K)

2.37, 2.41, 2.46, 2.50

4.73

4 4 4 4

2.48 2.46 2.43 2.46

5.20 5.14 4.99 5.09

4 (rac) (1:2, 2.40, 2.43, 2.46, 243 K) 2.49 5 (R) (1:2, 243 K) 2.47(17.3) 5 (rac) (1:2, 243 K)

2.42, 2.43, 2.46, 2.48

2.98(32.2)b

2.81/2.70(26.9) 5.04(50.7)

2.96m

2.78m

5.04, 5.01, 4.93

[0.00(0.1)] [0.00(0.2)] (OCH3); [0.03(0.7)] (CHO) [0.22] (NH); [( 0.2)] (C@O) [0.00( 0.1); 0.01( 0.1)] (Ar)

[0.02(1.1)]

3 (R) (1:1, 254 K) 2.44

(S) (1:1, 243 K) (R) (1:1, 243 K) (S) (1:2, 243 K) (R) (1:2, 243 K)

[(0.3)] [( 0.3)]

3.71(52.4) (OCH3); 8.18(160.6) (CHO); 6.20 (NH) 7.73(134.5), 7.83(123.7), (131.1) (Ar); (167.6) (C@O) 3.67(52.8) (OCH3); 7.69(134.2), 7.81(123.6), (131.7)(Ar); (167.8) (C@O) 2.28(41.5) (N(CH3)2); 3.66(51.2) (OCH3); ( 356.8) (N)

[( 0.1)]

[0.2(0.3)] (OCH3)

3.59, 3.61(OCH3); 8.24, 8.34 (CHO) 6.59 (NH); 3.06 (CH3, Rh salt) 3.58 (OCH3); 8.11 (CHO); 6.38 (NH); 3.07 (CH3, Rh salt)e 3.63 (OCH3); 7.85 (CHO) 6.46 (NH); 3.08 (CH3, Rh salt)e 3.58 (OCH3); 7.97 (CHO); 6.18 d (NH) 3.00 (CH3, Rh salt) 3.65 (OCH3); 7.49 (CHO); 6.38 d (NH) 3.00 (CH3, Rh salt) 3.58, 3.64, 3.65, 3.73 (OCH3); 7.39f, 7.49f, 7.98, 7.99 (CHO); 6.19, 6.21, 6.38 (NH)g; 2.99 (CH3, Rh salt)h 7.52, 7.59 (Ar); 2.95 (CH3, Rh salt)i 7.64; 7.74 (Ar); 2.96 (CH3, Rh salt)i 7.58, 7.62 (Ar) 2.86 (CH3, Rh salt) 7.65, 7.74 (Ar); 2.91 (CH3 Rh salt); 2.87, 2.89, 2.91 (CH3 Rh salt)j 2.87, 2.89, 2.91 (CH3 Rh salt) i 3.63(53.5) (OCH3); 7.68(134.1), 7.74(123.5) (Ar); 2.92 (CH3, Rh salt)i 3.62, 3.63, 3.64, 3.65 (OCH3); 7.74, 7.68, 7.60 (Ar); 2.87, 2.90, 2.91 (CH3, Rh salt)j

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2349

Table 1 (continued) SCH3

SCH2CH2

Adducts with Rh2TFA4, CDCl3 solution, 220 K 3 (S) (1:1)k 2.57(17.2) 3.08(31.8) 3 (R) (1:2)

l

SCH2CH2

CH

C@O

R

2.26/2.52(29.5) 4.89(49.6)

(171.8)

3.73(52.8) (OCH3); 8.24(160.9) (CHO); 6.45 (NH) 3.73(53.3) (OCH3); 8.22(161.7) (CHO); 6.58 (NH) 7.73(133.9), 7.83(122.9), (131.2) (Ar); (167.8) (C@O) 3.71(52.6) (OCH3); 7.75(135.0), 7.84(123.0) (131.4) Ar; 167.7 (C@O)

2.59 (17.6)

3.07(32.4)

2.26/2.50(29.6) 4.87(50.0)

(172.0)

4 (1:1)k

2.54(16.5)

3.02(31.7)m

2.76(25.4)m

5.11(49.4)

(175.4)

5 (1:1)k

2.55(16.5)

2.98(32.1)m

2.81(26.5)m

5.09(50.5)

(169.4)

(53.0, 53.8) (55.0)

(177.1, 177.5) (174.9)

3.44(67.4) (69.6)

(173.7) (172.7)

13

C CPMAS NMR, 298 K, ligands and their adducts with Rh2AcO4 1 (lig). (15.9, 17.7) (31.5, 32.1, 32.8, 33.3)n (17.8) (31.6)n 1 (1:0.5)p 7 (lig.)s 7 (1:1)t,u

2.17(16.9) (15.9)

2.61(32.6) (31.3)

2.00(30.9) (31.3)

( 336.3)o (N) (24.2,24.2,192.5) (Rh2AcO4); ( 338.5)r (N) 2.41(43.0) (N(CH3)2); 3.77(52.6) (OCH3) (40.2, 47.6) (NCH3); (51.3) (OCH3); (23.4, 190.8); (Rh2AcO4), ( 358.2) (N)

a All values were given in ppm. 1H chemical shifts (ppm) were given with respect to DSS or TMS signals (0 ppm), depending on the solvent (D2O or CDCl3); 13C chemical shifts (in parentheses, ppm) were referred to the solvent signal (CDCl3, 77.0 ppm) or DSS signal (0 ppm, D2O solutions). Adduct formation sifts Dd = dadduct dligand (ppm) (or Ddadd) were given in square brackets. All temperatures were read out from instrument panel and corrected; see Section 4. b 1 H chemical shift read out from 2D 13C, 1H g-HSQC spectrum. c 1 H and 13C (in parentheses) adduct formation shifts for the Rh2AcO4 and ligand mixtures. d The signals of SCH2CH2 moiety were not identified unambiguously and they were omitted in the table. e The 1H NMR spectrum of 1:0.5 sample showed up at 254 K an additional OCH3 signal of free Rh2MTPA4, this signal vanished in course of titration. f The signal not observed at 231 K due to broadening, see Figure 4. g At 231 K NH signals appeared at 6.53, 6.32 and 6.30 ppm, see Figure 4. h At 231 K the signal split into three components, see Figure 4. i The 1H NMR spectrum of 1:0.5 sample (243 K) showed up two OCH3 signals, of free dirhodium salt and R/4S adduct. j The 1H NMR spectrum of 1:0.5 sample (243 K) showed up three OCH3 signals, one of free dirhodium salt and two of R/4S and S/4S adducts, respectively. k 1 H(13C) adduct formation shift (Ddadd [ppm], calculated as differences between chemical shifts of an adduct at decreased temperature and ligand at 303 K: 3: 0.54(1.7) (SCH3), 0.62(2.0) (SCH2), 0.29/0.38( 2.2) (SCH2CH2), 0.14( 0.6) (CH), ( 0.2) (C@O), 0.02(0.4) (OCH3), 0.06(0.3) (CHO), 0.25 (NH); 4: 0.51(1.6) (SCH3), 0.48(5.1) (SCH2), 0.42/ 0.32( 4.7) (SCH2CH2), 0.09( 0.4) (CH), (2.9) (C=O), this value reduced to 0.2 ppm if ligand spectrum taken at 220 K was used for the calculations, 0.00( 0.6), 0.00( 0.8), (0.1) (Ar), (0.2) (C@O); 5: 0.54(1.2) (SCH3), 0.53(4.1) (SCH2), 0.41/0.31( 4.3) (SCH2CH2), 0.06( 0.3) (CH), ( 0.1) (C@O), 0.04( 0.2) (OCH3), 0.06(0.8), 0.03( 0.6), ( 0.3) (Ar), ( 0.1) (C@O). l The 1H NMR spectrum of racemic 3 measured in the same conditions contains three signals in CHO and NH ranges (Fig. 6), CHO: 8.22, 8.19 and 8.18 ppm; NH 6.70, 6.67 and 6.55 ppm. m The assignments can be opposite. n The signal arising from SCH2CH2 moiety, not assigned. o 15 N signal, signal width at the half-height: 32 Hz. p A sample obtained by the evaporation of water solution containing Rh2AcO4 and 1 in the molar ratio of 1:1. r 15 N signal, signal width at the half-height: 370 Hz. s Chemical shifts of neat ligand. t A sample obtained by the evaporation of CDCl3 solution containing Rh2AcO4 and 7 in the molar ratio of 1:1. u 13 C adduct formation shift Ddadd (ppm), calculated as differences between 13C chemical shifts of 1:1 adduct in the solid state and neat ligand (ppm): 1.0 (SCH3), 1.3 (SCH2), 0.4 (SCH2CH2), 0.2 (CH), 1.0 (C@O), 2.8/4.6 (NCH3), 1.3 (OCH3).

indicating that all of the added ligands were bonded by the dirhodium salt. The bonding site in a ligand was another factor that was considered. Previous investigations on the adducts of dirhodium salts with b-lactams30 suggested the following coordination selectivity: C–S–C > C@O > C–O. As an aminoacid, methionine 1 is expected to have a zwitterionic structure, containing –COO and protonated – N+H3 groups. Conversely, carboxylic acids are generally weak and the N-adduct of 1 could not be a priori excluded. Apart from the nitrogen atom, the complexation could occur via either the sulfur or oxygen atoms. Three complexation modes of the carboxylic group should be considered: by @O, –OH or, assuming a zwitterionic structure, an ionized –O group. In the case of salts 1-HCl and 2-HCl, nitrogen centers were protonated by a strong acid, and were expected to be inactive in complexation. In order to explore the experimental NMR data, we attempted to calculate Ddadd (1H and 13C) for some adducts of methionine. Calculations were performed by the application of density functional theory (DFT), using a GAUSSIAN package.31 The Ddadd values were obtained as the difference between the calculated chemical shifts for the adducts and the corresponding chemical shifts of the free ligand. In this way the errors arising from the calculation method and recalculation of shielding scale to chemical shift scale

were expected to cancel out. The dependence of the calculated chemical shifts on conformations and arrangements of the COOH and NH2 groups in methionine appeared to be the main difficulties. Calculations performed for twelve arbitrarily selected conformers of 1 showed up theoretical 1H chemical shifts within the ranges from 2.9 to 3.7 ppm for CH, 1.2–1.8 and 1.7–3.1 ppm for CHCH2 pro-S and pro-R hydrogens, 2.7–3.6 ppm for SCH2, and 2.1– 2.2 ppm for SCH3. Analogous ranges for the 13C chemical shifts spanned 59–64 ppm (CH), 36–46 ppm (CHCH2), 44–47 ppm (SCH2), and 26–27 ppm (SCH3). The chemical shift of the C@O signal varied from 180 to 188 ppm; 15N signals appeared within the range of 322 to 355 ppm. Experimental and theoretical 1H chemical shifts correlated badly (r2 from 0.54 to 0.92, depending on the structure); better results (r2 >0.95) were obtained for 13C chemical shifts. Additionally, the structures exhibiting the lowest energy provided the worst correlations. Evidently, a model based on the isolated molecule in vacuum was inadequate for our experimental conditions. Since the population of the ligand and adduct conformers in the solution were unknown, and the variations of chemical shifts arising from the different conformers were larger than experimental Dd values usually observed, these parameters could not be calculated precisely. However, in order to obtain at least rough data, we performed chemical shift calculations for a

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H

H 3.17 1.42 H (46.9)

2.18 (26.7) S

(39.0) H 2.28

N

H (59.4)

(-0.9) H 0.58

(-2.2)

Rh

O

H 1.37

H

H (0.0)

H -0.07

N

(-0.2) O

H

(1.9)

-0.10 -0.14 H (0.8)

-0.11 (-0.6)

H O

S

(-2.2)

(-3.1)

H 0.81

O

H

H

-0.04 0.57 (0.2) H S

S

(183.7)

H 3.26

Rh -0.07 (0.2)

O

N

0.58 0.04 (4.8) H

0.53 (3.5)

H 1.15

O H

N

H (-0.3)

H 1.72 Rh

O

(-0.1) O H

H 0.09 0.21 H (0.01)

0.03 (0.0) S

(-0.9) H 1.17

1

N

H (3.2)

H 0.29

O (18.6)

0.52(3.6)

0.47(4.0) Rh

-0.09(-0.1)

S 0.66(-2.1)

-0.01(0.2)

Rh

O H

13

Figure 3. Calculated H( C) chemical shifts for an arbitrarily selected conformer of methionine 1 and calculated adduct formation shifts (Ddadd = dadduct dligand) for its hypothetical S-Rh, N-Rh, and O-Rh adducts. The last structure shows calculated Ddadd for the adduct of 1-methylsulfanylbutane. All values are given in units of ppm.

few adducts with various complexation modes assuming the same conformation for free ligand and ligand in an adduct (Fig. 3). For the sake of comparison, calculations were also repeated for the simple model, methylsulfanylbutane, which contains one heteroatom. According to our theoretical findings, S-Rh adducts were expected to exhibit the largest positive Ddadd for the hydrogen and carbon next to the sulfur atom (CH3SCH2 group). Large positive Ddadd (1H) and negative Ddadd (13C) values should be observed for the next CH2 group. In the case of N-Rh and O-Rh adduct type, the Ddadd for the CH3SCH2 group was expected to be relatively small in comparison with the remaining atoms in the molecule. Large Ddadd (13C) of the carbonyl group was expected in the case of complexation via a C@O oxygen. The same relationships were found for 1-methylsulfanylbutane, which contains a single heteroatom in the molecule. Experimental results generally followed the findings for the SRh adduct type. The largest Dd (1H)s from 0.25 to 0.45 ppm were found for the CH3SCH2CH2 hydrogen atoms. Positive Dd (13C)s, of ca. 2 ppm were observed for the CH3SCH2 carbon atoms (i.e., atoms bonded to the sulfur), whereas the SCH2CH2 carbon atoms showed negative values, from 0.8 to 0.6 ppm (Table 1). In order to validate our calculations using different adduct types, we measured the Rh2TFA4 adducts of N-formyl leucine methyl ester 6 in CDCl3 (1H and 13C NMR data are given in Section 4). The lack of a sulfur atom in the molecule and the protected NH group forced complexation via the oxygen atoms. The largest Dd (13C) was expected for one or both carbonyl groups. In fact, the COOCH3 group shows the Dd (13C) of 0.1 ppm, whereas Dd (13C) of the CHO reached a value of 5.8 ppm. The conclusion on the complexation site is obvious in this case. Previously, the adduct formation shifts of a nitrogen atom were used as a convenient proof of complexation. In the case of the

amines, Ddadd (15N) varied from ca. 5 to 30 ppm.23 Our attempts to measure the 15N NMR spectra by an inverse technique in D2O solution were unsuccessful, probably due to the low adduct concentration and broad signals. In order to overcome these difficulties, we performed NMR measurements in the solid state, using 13 C and 15N CPMAS NMR. Samples containing methionine and Rh2AcO4/methionine mixtures in the molar ratios of 1:0.5 and 1:1 were obtained by evaporation of suitable solutions to dryness (see Section 4). The 13C CPMAS NMR spectrum of methionine showed two sets of narrow signals, indicating the presence of two non-equivalent molecules in the solid state. However, the 15 N CPMAS NMR spectrum showed only one narrow 15N signal, at 336.6 ppm. The 13C CPMAS NMR spectra of both adducts contained broad irregular signals indicating the presence of amorphous or/and polymorphic material. The 15N CPMAS NMR spectra contained one broad signal at ca. 338 ppm. The lack of a significant 15N chemical shift change excluded the nitrogen atom as a binding site. Our attempt to measure Rh2TFA4 adducts with methionine in D2O was unsuccessful, due to fast sample decomposition. The third salt studied, Rh2MTPA4, was insoluble in D2O. 2.2. Complexation of 3, 4 and 5 with Rh2AcO4 in CDCl3 Rhodium tetraacetate, poorly soluble in CDCl3, was dissolved over the course of a titration with 3–5. Typically, the mixture contained Rh2AcO4 and the ligand in molar ratios of ca. 1:1 at the beginning of the titration (1:0.5 sample) and ca. 1:2 at the end (1:2 sample). No significant change in Dd occurred during the titration; only the addition of ligand excess decreased Dd. The largest 1 H and 13C Dd were observed for the CH3S and SCH2 atoms (Table 1), indicating the sulfur atom as a binding site. Since the ligand exchange was fast on the NMR timescale, the titration experiment did not answer whether the mixture contained 1:2 adduct or a

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mixture of adduct and free ligand. Due to the difficulty in controlling the solution composition in a two-phase sample, further measurements using low temperature NMR were not continued for these adducts. 2.3. Complexation of 3, 4 and 5 with (4S)-Rh2MTPA4 in CDCl3 Typically, NMR measurements for these adducts were performed at reduced temperature. A temperature decrease caused signal broadening, especially at the beginning of the titration (1:0.5 and 1:1 samples), but enabled us to observe the signals of all the species in the 1:2 and 1:2.5 samples. The 1H NMR signals of SCH3 and OCH3 groups appearing as singlets were the most diagnostic. Due to the large 1H multiplets of the SCH2CH2 moiety and its overlap with the SCH3 and OCH3 signals, the unambiguous identifications of these multiplets were difficult; their chemical shifts are omitted in Table 1. The 13C chemical shifts for the adducts were taken from 2D 13C,1H-HSQC spectra. Since the detection of quaternary carbon atom signals required additional experiments (2D 13 1 C, H-HMBC), these values were often omitted as unimportant for further discussion. In order to explore the phenomena related to the chirality, the adducts of both enantiomerically pure and racemic ligands were investigated. The 1H NMR spectra of enantiomerically pure ligands 3 (303 K, 1:0.5 and 1:1 samples) contained one set of signals each, as was expected. If racemic 3 was used, the spectrum was simply the

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combination of spectra of two diastereoisomers, (R,4S) and (S,4S) A temperature decrease (254 K) resulted in signal broadening; nevertheless the CHO, NH CH, and CH3 signals could be identified. The OCH3 signal of the Mosher’s acid residue (1:0.5 sample, 254 K) split, indicated the presence of a non-complexed and bonded dirhodium salt in the solution. The signal of free salt vanished in the spectrum of the 1:1 sample. Over the course of titration, the 1H chemical shifts changed slightly, although signal splitting arising from the presence of 1:1 and 1:2 adducts was not observed, probably due to the minimal chemical shift differences between these signals and the chemical shift averaging. The 1:2 mixture of (4S)-Rh2MTPA4 and enantiomerically pure 3 showed one set of signals in the 1H NMR spectra, assigned to (R,R,4S) [or (S,S,4S)] isomers, depending on the enantiomer used. At 254 K, the signals of the non-complexed 3 appeared in the spectrum of the 1:2.5 mixture. In contrast, the spectra of the 1:2 sample of racemic 3 contained additional signals arising from (RS,4S) adduct (Fig. 4). At 254 K the CHO group showed up five signals assigned to (S,S,4S), (R,R,4S), and (RS,4S) diastereoisomers and to a non-complexed ligand. At 231 K two of these signals vanished due to broadening. The chemical shifts of the NH hydrogen depended on the temperature; at 231 K four doublets were visible, probably the result of two signals overlapping. The signal of the OCH3 group of the Mosher’s acid residue consists of three components, arising from three diastereoisomers. The SCH3 and OCH3 groups in the ligand provide five and four signals respectively (thus,

Figure 4. Partial 1H NMR spectra of (4S)-Rh2MTPA4 and rac-3 mixture (CDCl3 solution, substrate to ligand in the molar ratio of 1:2.5, decreased temperature). The following ranges were seen: the range of CHO signals (231 and 254 K) (a); the range of NH signals (231 and 254 K) (b), the range of OCH3, and SCH3 signals (231 K) (c). The spectra show the signals of three diastereoisomers (R,R,4S), (S,S,4S), and (RS,4S) and the free ligand. Signals were identified by comparison with the spectra of enantiomerically pure adducts, (4S)-Rh2MTPA4-(S)-3, and (4S)-Rh2MTPA4-(R)-3.

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Figure 5. Partial 1H NMR spectra of (4S)-Rh2MTPA4 and 4 mixture (CDCl3 solution, various substrate to ligand molar ratios, 243 K); enantiomerically pure (a) and racemic ligands (b). The signals of SCH2CH2 hydrogens form large broad multiplets and appeared in the spectra as baseline distortions.

two signals overlapped). The presence of additional signals in the 1:2 sample and the lack of such signals in the 1:1 sample proved the stepwise formation of the 1:1 and 1:2 adducts. Similar phenomena related to chirality were observed in the case of the Rh2MTPA4 adduct with 4. The signals of the SCH3 and OCH3 groups illustrate these effects (Fig. 5). The 1:0.5 mixture of Rh2MTPA4 and enantiomerically pure 4 illustrated in the 1H NMR spectrum (243 K) the signals of SCH3 and OCH3 groups arising from the (S,4S) [or (R,4S)] isomer, and additionally the signal of noncomplexed (free) Rh2MTPA4 salt. Over the course of the titration, the signal of the free rhodium salt vanished, and the signal of the 1:2 adduct appeared. Finally, singlets assigned to the OCH3 and SCH3 groups, arising from the (S,S,4S) [or (R,R,4S)] adduct were visible. In the case of racemic 4, the spectrum of the 1:1 mixture contains two doublets arising from the OCH3 and SCH3 groups respectively, assigned to (S,4S)- and (R,4R)-isomers. The spectrum of the 1:2 sample showed three signals for the Rh2MTPA4 salt and four signals for the SCH3 group, arising from the (R,R,4S)-, (S,S,4S)-, and (RS,4R)-isomers. The remaining signals (Ar and CH) behaved similarly, although the effects were not so clearly visible due to the multiplicity of these signals. The spectra of Rh2MTPA4 and 5 mixtures exhibited very similar features. The 1H NMR spectrum (243 K) of the 1:0.5 sample contained the OCH3 signal of non-complexed Rh2MTPA4, which vanished over course of the titration. The corresponding signal in the adduct appears either as a singlet (enantiomerically pure 5) or as a doublet (racemic ligand). The CO2CH3 and SCH3 methyl groups in the 1:2 sample produced either one singlet each for enantiomerically pure 5, or two sets of four signals each for racemic 5. The OCH3 signal of the Rh2MTPA4 core appeared in these cases as a singlet or triplet, respectively. 2.4. Complexation of 3, 4 and 5 with Rh2TFA4 in CDCl3 The NMR titration at 220 K was performed for Rh2TFA4 and 3 using both the enantiomerically pure and racemic ligand. At the start of the titration (1:0.5 sample), the signals were broad and most of the adducts were deposited on the bottom of the NMR tube. Over the course of the titration, the solid dissolved. Only minor 1H shift differences between the 1:1 and 1:2 samples were observed (Table 1). The spectra of the 1:1 and 1:2 samples differed, depending on the ligand used; enantiomerically pure or racemic.

Additional signals in the spectrum, assigned to R/S adduct, appeared for the NH and CHO groups (Fig. 6). Thus, the two ligands mutually recognized each other in the 1:2 adduct. This effect suggests an interesting extension of the ‘dirhodium NMR method’, allowing us to determine the enantiomeric purity of the ligand without the use of expensive enantiomerically pure dirhodium derivatives. In order to further explore this feature, we performed measurements with phthaloyl derivatives of methionine, 4 and 5. Unfortunately, we did not observe any such effects for these ligands, despite NMR measurements at low temperature (220 K). The signals of the non-complexed ligand appeared at the beginning of the titration (1:0.5 and 1:1 samples); thus the free ligand was present in the equilibrium with an adduct in the mixture. The experiment did not answer whether one adduct or a mixture of species was in the samples. There were no differences between the spectra of the pure isomer and racemic ligands. On the other hand, signals in the spectra were quite broad, and the observation of subtle effects was rather difficult. This indicates that either mutual ligand recognition did not occur, or that the differences between spectra were too small to be observed. All the signals of the Rh2TFA4 adducts were identified unambiguously by 2D 13C–1H correlation spectra (HSQC, HMBC) with the exception of those in the SCH2CH2 group. Hydrogen atoms SCH2CH2 are chemically non-equivalent due to the presence of a stereogenic center, and produced two 1H signals (two multiplets). In contrast, the SCH2 atoms appeared as one multiplet. This feature allowed us to identify these signals in the Rh2TFA43 adduct. However, the corresponding signals in the Rh2TFA4-4 and Rh2TFA4-5 adducts appeared as single broad multiplets, and assignments were carried out assuming the 13C signals order as in the adduct of 3. The assigned chemical shifts were used for the calculation of a full set of 1H and 13C Ddadd values (Table 1, in the footnote). The Ddadd values were obtained using spectra of adducts taken at reduced temperature and ligand spectra taken at 303 K. A decrease in temperature did not significantly change the ligand chemical shifts, with the exception of the carbonyl signal of 4 (172.4 ppm at 303 K, 175.2 ppm at 220 K). Generally, the experimental findings followed the results of theoretical calculations for the S-Rh adduct type. The largest positive Ddadd values adopted by CH3SCH2CH2 hydrogen atoms; CH3SCH2 carbon atoms exhibited positive Ddadd, in contrast to SCH2CH2 which showed

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points indicated that more than two species were present in the solution. Thus, the stepwise formation of the two adducts, 1:1 and 1:2 was in agreement with these findings. The complexation of Rh2TFA4 with the formyl derivative of leucine methyl ester 6 was the third process studied. This ligand was expected to bond to dirhodium salt via the oxygen atom only. Over the course of the titration, a band attributed to the rhodium salt moved by ca. 20 nm only, and its intensity increased. The appearance of this spectrum differs from those observed for Rh2MTPA4-3 and Rh2MTPA4-4. Additionally, the measurement confirmed complexation via the oxygen atom under our experimental condition, which was consistent with our previous NMR findings (see above). This result suggested the possibility of a third kind of adduct in the CDCl3 solution, appearing at the beginning of the titration, in the presence of an excess of rhodium salt. Such adducts were expected to contain two dirhodium cores: one bonded via the S-site and the second via the O-site (in case of 3 via CHO group). These ternary compounds were expected to vanish over the course of the titration, due to the replacement of O-Rh with S-Rh adducts. 2.6. Two-phase samples

Figure 6. Partial 1H NMR spectra of Rh2TFA4 and 3 mixtures (CDCl3 solution, substrate to ligand in the molar ratio of 1:2.5, 220 K). The ranges of the CHO and NH signals are shown. Bottom trace corresponds to the adduct of single enatiomer of 3; upper trace corresponds to the adduct of the racemic ligand. Red asterisks indicate the signals of the free ligand.

negative Ddadd values. The large positive and negative Ddadd (13C) values for both SCH2CH2 atoms in adducts of phthaloyl derivatives 4 and 5 are noteworthy. This effect was also observed in the case of Rh2AcO4 4. The values for the remaining atoms ranged from 1 to 1 ppm, with the exception of C@O signal of 4 (2.9 ppm). However, this value was reduced to 0.2 ppm if both the ligand and adduct spectra taken at 220 K were used as the base of calculations. 2.5. Absorption electronic spectroscopy in the visible range of 4, 5 and 6 adducts in CDCl3 solution For the sake of comparison, we performed some measurements using electronic absorption spectroscopy in the visible range (vis) (Fig. 7). Titration of Rh2MTPA4 in CDCl3 with 3 or 4 provided similar spectra: free dirhidium salt absorbed at 641 nm; over the course of the titration two bands showed up, assigned to the 1:1 (ca. 596 nm) and 1:2 adducts (537 nm). The lack of isosbestic

An interesting approach to the investigation of dirhodium adducts was the use of two-phase samples. In fact, the study of Rh2 AcO4 adducts in CDCl3 was an example of such a method. Rhodium tetraacetate was practically insoluble in CDCl3, and dissolved over the course of the titration. Complexation was a driving force, transporting the rhodium salt to the solution as an adduct. We attempted to apply this method to the Rh2MTPA4/1/D2O and Rh2AcO4/5/D2O mixtures. In the first case, the sample contained a D2O solution of 1 and Rh2MTPA4, insoluble in D2O. The second mixture consisted of Rh2AcO4 in D2O solution and 5, insoluble in water. Both experiments were unsuccessful; the insoluble component did not dissolve in D2O despite the use of an ultrasonic bath. However, application of a D2O/CDCl3 mixture yielded red CDCl3 solutions of the Rh2MTPA4 adduct with methionine 1 and Rh2AcO4 adduct with 5, respectively. Thus, the application of two solvents enabled us to transport the insoluble component to the organic phase. The 1H NMR spectra of the Rh2MTPA4-1 adduct in CDCl3 were difficult to interpret, due to the broad signals of the ligand. Measurements at a decreased temperature (231 K) allowed us to observe only a broad OCH3 multiplet. The shape of this signal differed depending on the ligand used; enantiomerically pure or racemic. One component of the multiplet was identified as the signal of the non-complexed rhodium. Unfortunately, the results were difficult for quantitative analysis. Nevertheless, this method of sample preparation appears to be promising in future spectroscopic investigations and possibly in organic synthesis.

Figure 7. Absorption electronic spectra (visible range) of Rh2MTPA4 and Rh2TFA4 adducts in CDCl3; titration of Rh2MTPA4 by 3 (a), Rh2MTPA4 by 4 (b), Rh2TFA4 by 6 (c). Green curves correspond to dirhodiun salt solutions; the next curves correspond to samples containing dirhodium salts and ligands in the molar ratio from 1:0.5 to 1:2.5 (step 0.5). The initial concentration of rhodium salt was ca. 1 mM; 0.5 cm cell was used.

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2.7. Complexation of N,N-dimethylmethionine methyl ester 7 The presence of N(CH3)2 and COOCH3 groups excludes the zwitterionic structure of this ligand. In theory, all complexation sites (S, N and O) are able to bond to the dirhodium salts. Competition between S and N centers was expected. We examined the complexation of 7 with Rh2AcO4 in the liquid and solid state. The 1H NMR spectra measured in CDCl3 solution suffered from broad and overlapping signals, despite various temperatures (303 or 231 K). Not all signals could be identified; careful examination of the 2D 13C,1H-HSQC spectra allowed us to see some 13C chemical shifts (Table 1). We were not able to unambiguously identify the signals of the N(Me)2 groups in the spectrum of the 1:0.5 sample at 303 K; however decreasing the temperature (231 K) revealed two signals of these groups, at 40.4 and 47.5 ppm. Similar 13C chemical shift dispersion was previously observed in the adducts of amines R*N(CH3)2 (R* denotes a chiral moiety).27 The dispersion originated in the stereogenic center close to the nitrogen atom, and slow inversion at the nitrogen atom caused by complexation. In case of 7, the dispersion suggested the nitrogen as the binding site. The HSQC spectrum of the 1:0.5 mixture taken at 231 K contained some additional signals, for instance, the two signals of Rh2AcO4 methyl groups. This splitting disappeared over the course of the titration. Such features of the spectrum can be tentatively explained by assuming the presence of a 2:1 adduct, containing one ligand molecule and two non-equivalent dirhodium units; one bonded via the nitrogen and the second by the sulfur atom. Over the course of the titration, this compound transformed to the 1:2 N-type adduct. In order to eliminate dynamic processes in the solution, we performed measurements in the solid state by the 13C and 15N CPMAS NMR techniques. The 13C spectrum contained broad signals, which were assigned by comparison with the spectrum of neat (liquid) ligand (Table 1). The dispersion of N-methyl signals (40.2 and 47.6 ppm) also appeared in the solid phase. The adduct formation shifts were calculated using 13C CPMAS NMR and neat ligand spectra. Generally, the largest Ddadd values were observed for two Nmethyl groups ( 2.8 and 4.6 ppm), and for CH atom (2.2 ppm). Minor values adopted SCH3 and SCH2 carbon atoms, in contrast to adducts of 1–5, measured in CDCl3. This Ddadd pattern suggested that rather N(CH3)2 than SCH3 group is the complexation site. Nitrogen-15 adduct formation shift is generally a good proof of complexation. The complexation of amines occurring via the nitrogen atom produces negative Ddadd values 15N, from 4 to 40 ppm.23 Unfortunately, in regard to our investigations this parameter was not diagnostic. Since 7 was a liquid, we had to use 15N chemical shifts measured under various conditions (CDCl3 solution for the ligand and the solid state for the adduct). The Ddadd (15N) value of 1.4 ppm, was too small to conclude on the complexation site.

3. Conclusion Our results led to the following conclusions: (i) Dirhodium salts (Rh2AcO4, Rh2TFA4, and Rh2MTPA4) form with methionine and its derivatives, 1:1 and 1:2 axial adducts, depending on the substrate to ligand molar ratios. The complexation of methionine occurred in D2O solution despite the competition of the ligand with water molecules. Complexation process can be monitored either by NMR spectroscopy (especially at reduced temperature) or by electronic absorption spectroscopy in the visible range (vis). Analysis of adduct formation shifts, as well as DFT calculations indicated that the sulfur atom is the complexation site in ligands 1–5 and 7.

(ii) Typically, fast ligand exchange (in the NMR timescale) occurs at room temperature (303 K). As a consequence, signals in averaged positions or broad signals were observed in the spectra. The adduct of Rh2AcO4 and 1 (D2O solution) was a typical example. However, in the case of adducts with Rh2TFA4 and Rh2MTPA4 decreasing the temperature within the range 220 to 254 K slowed down the exchange rate and enabled us to observe the signals of all species in the solution. (iii) The signals of all the Rh2MTPA4 diastereomeric adducts [(S,S,4S), (R,R,4S), and (RS,4R)] were observed in low-temperature 1 H NMR spectra. The combination of 1H NMR spectra of (S,S,4S)and (R,R,4S)-isomers differs from the spectrum of the adduct of racemic ligand, due to additional signals arising from the (RS,4R)-isomer. Thus, the two ligands in both axial positions of the dirhodium unit recognized each other, despite the distance between them. (iv) Similar effects were observed in the case of the Rh2TFA4-3 adduct. The spectra of 1:2 adducts were different depending on the ligand used; enantiomerically pure or racemic. Unfortunately, these phenomena were not observed for the Rh2TFA4-4 and Rh2TFA4-5 adducts. Nevertheless, mutual ligand recognition in the two axial positions in Rh2TFA4 suggests the interesting extension of NMR dirhodium method, namely the determination of the enantiomeric purity of the compound by NMR methods without the need for an expensive enantiomerically pure dirhodium salt. (v) Application of the two-phase CDCl3/D2O mixture resulted in the extraction of an insoluble component to the organic phase as the adduct.

4. Experimental (R)- and (S)-methionine 1 were commercially available and were purchased. The following aminoacid derivatives were prepared according to the published procedures: methionine methyl esther 2 (as an HCl salt) by esterification of methionine with 2,2dimethylpropane;32 N-formyl derivative 3 by formylation of methionine methyl ester with ammonium formate;33 N-phthaloyl methionine 4 from methionine and phthalic anhydride;34 Nphthaloyl methionine methyl ester 5 from 2 and phthalic anhydride, leucine formyl derivative 6 by formylation of leucine methyl ester;33 and N,N-dimethylmethionine methyl ester 7 from methionine methyl ester via reaction with formaldehyde and NaBH3CN.35 The hydrochloride salts of the aminoacids were prepared by acidification of the aminoacid with HClaq in H2O solution and then evaporation of the solvent in vacuo. Rhodium(II) tetraacetate and tetratrifluoroacetate were purchased; the dirhodium tetra-(S)-amethoxy-a-(trifluoromethyl)-phenylacetate dimer (Mosher’s acid derivative, Rh2MTPA4) was prepared from enantiomerically pure (S)-Mosher’s acid (commercially available) and rhodium(II) tetraacetate according to a published procedure.36 1 H and 13C NMR spectra in the liquid phase (CDCl3, D2O and neat liquid compounds) were measured on a Bruker Avance DRX500 spectrometer, using 5 mm TBI probe equipped with zgradient coil. One-dimensional 1H NMR spectra was measured with the following parameters: an acquisition time of ca. 2.5 s, relaxation delay of 1 ms, pulse width of 2.5 ls (ca. 30°) and spectral width of 6500 Hz; 32 K points matrix was used for both data acquisition and Fourier transformation, giving spectral resolution of 0.2 Hz per point. 13C NMR chemical shifts of non-complexed ligands have been taken from one-dimensional spectra recorded with the following parameter values: 2.2 s for the acquisition time, 500 ms for the relaxation delay and 4.3 ls (ca. 33°) for pulse width. Spectral width of 15200 Hz and 64 K points matrix was used for both data acquisition and Fourier transformation, giving a spectral resolution of 0.23 Hz/point. 13C chemical shifts of adducts, due to low sample concentration, were measured using 2D inverse

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gradient correlation techniques. Both experiments, 13C,1H-gHSQC (‘invietgs’ Bruker’s pulse program: phase sensitive, E/A gradient selection with decoupling during acquisition) and 13C,1H-gHMBC were applied with the following parameters: a 2048  512 matrix zero-filled to 2048  1024 prior to FT, an acquisition time of 0.25 s, relaxation delay of 1.2 s, and from 4 to 8 transients per experiment. The final spectroscopic resolution of 2 Hz per point (1H domain) and ca. 10 Hz per point (13C domain) was achieved. All 1H and 13 C chemical shifts were referred to the TMS or DSS signal (0 ppm), depending on the solvent used. The carbon signal of CDCl3 was also used as a secondary reference (77.0 ppm with respect to TMS signal). Sample temperatures (K) were read out directly from the instrument panel and corrected using the calibration curve, prepared on the basis of a methanol thermometer. Complexation was investigated by the use of titration experiments. To NMR tubes, containing ca. 10 mg of dirhodium salt and 0.7 ml of D2O or CDCl3 (depending on ligand and rhodium salt solubility), suitable amounts of ligand solution with known concentration were added. Typically, the samples containing 1:0.5, 1:1, 1:1.5, 1:2, and 1:2.5 rhodium salt to ligand molar ratio were prepared and measured. The following convention of sample description was used in the whole text; for example 1:1.5 sample means that to the NMR tube metal salt and ligand in the molar ratio of 1:1.5 was added. The two-phase method of sample preparation was based on the mixing of two solutions, methionine in D2O and Rh2MTPA4 in CDCl3, and removal of the water layer. As an alternative, a D2O solution of Rh2AcO4 and a CDCl3 solution of 5 were used. Samples for the solid state NMR were prepared by dissolving the dirhodium tetraacetate (100–150 mg) and the corresponding amount of aminoacid in water, and then evaporation of the solvent in vacuo. 13C and 15N CPMAS NMR spectra were performed on a Bruker 500 WB Avance II spectrometer, equipped with 4 mm broadband probe. All measurements were taken at 298 K. The basic HartmannHahn cross polarization pulse sequence was used. The following parameters values for 13C CPMAS NMR were applied: spectral width of 250 ppm, an acquisition time of 0.02 s, relaxation delay of 30 s, contact time for spin lock of 2 ms, and 1246 points matrix zero-filled to 4 K for data acquisition and FT, giving spectral resolution of 7.6 Hz per point. Also, 4000 scans were collected for each experiment. The parameters for 15N CPMAS NMR were the following: 498 ppm (spectral width), 0.035 s (an acquisition time), 10 s (a relaxation delay), and 4 ms (spin lock). Typically, ca. 16000 scans were collected; 1764 points matrix zero-filled to 2 K giving spectral resolution of 12 Hz per point was used. All CP MAS NMR experiments were performed applying a 10 kHz spin rate. Originally, the CP MAS NMR spectra were referred to glycine [d(13C)glycine = 43.3 ppm in respect to the TMS signal at 0 ppm; d(15N)glycine = 347.6 ppm in respect to the CH3NO2 signal at 0 ppm]. The NMR data (1H and 13C chemical shifts and adduct formation shifts) for ligands 1–5 and 7 are shown Table 1. 1H chemical shifts, 13 C chemical shifts (in parentheses) and corresponding adduct formation shifts (in square brackets) (in ppm) for the 1:0.5 mixture of Rh2TFA4 and 6 in CDCl3 were as follows: 0.93(21.9, 22.7) [0.13/ 0.7( 0.3/0.0)] (isoprop. CH3); 1.67(24.8) [0.18(0.0)] (isoprop. CH); 1.56/1.68(41.8) [0.23/0.24(0.3)] (CH2); 4.73(49.3) [0.73(1.6)] (CH); 3.75(52.4) [0.15(0.5)] (OCH3); 5.94 [1.07] (NH); 8.21(160.5) [0.57(5.8)] (CHO); (173.0) [ 0.1] (C@O). Absorption electronic spectra in the visible range were made on JASCO spectrometer. The solutions of dirhodium salts (ca. 10 3 M) were titrated by concentrated ligand solution directly in the spectrometer cells. Deuterated solvents (D2O and CDCl3) were used in order to achieve the same conditions as in the NMR measurements. All theoretical calculations were performed using GAUSSIAN 03 package.31 Structure optimisations were performed using DFT (Density Functional Theory), at B3LYP/3-21G theory level. NMR

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shielding calculations (GIAO) were performed using B3LYP method with LANL2DZ basis set for Rh and 6-311G(2d,p) basis set for C, H, N, O, and S atoms. A shielding scale was converted to a chemical shift scale using shielding values for TMS, provided by GAUSSIAN package (B3LYP/6-311G+(2d,p) GIAO; 31.8821, and 182.4656 ppm for 1H, and 13C, respectively). Adduct formation shifts were calculated as a difference between chemical shifts in adduct and chemical shifts of corresponding signals in a free ligand. Acknowledgements This work was partially supported by the scientific network of the Ministry of Science and Higher Education of Poland (decision 68/E-61/BWSN-0126/2008) ‘New applications of NMR spectroscopy in chemistry, biology, pharmacy and medicine’. References 1. Cotton, F.; Walton, R. Multiple Bonds Between Metal Atoms, 2nd ed.; Claredon Press: Oxford, 1993. p 431, Chapter 7. 2. Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic Chemistry; Oxford University Press: Oxford, 2001. p 1057. 3. Doyle, M. J. Org. Chem. 2006, 71, 9253–9260. and references cited therein. 4. Hansen, J.; Davies, H. Coord. Chem. Rev. 2008, 254, 545–555. and references cited therein. 5. Frelek, J.; Klimek, A.; Rus´kowska, P. Curr. Org. Chem. 2003, 7, 1081–1104. 6. Frelek, J.; Jagodzin´ski, J.; Meyer-Figge, H.; Sheldrick, S.; Wieteska, E.; Szczepek, J. Chirality 2001, 13, 313–321. 7. Frelek, J. Tetrahedron: Asymmetry 1999, 10, 2809–2816. 8. Frelek, J.; Szczepek, J. Tetrahedron: Asymmetry 1999, 10, 1507–1520. 9. Frelek, J. Pol. J. Chem. 1999, 73, 229–239. 10. Frelek, J.; Geiger, M.; Voelter, W. Curr. Org. Chem. 1999, 3, 117–146. 11. Duddeck, H. Chem. Rec. 2005, 5, 396–409. and references cited therein. 12. Xue, W.; Kühn, F. Eur. J. Inorg. Chem. 2001, 2041–2047. and references cited therein. 13. Clarke, M.; Fuchun, Z.; Frasca, D. Chem. Rev. 1999, 99, 2511–2533. 14. Aguirre, D.; Chitofides, H.; Angeles-Boza, A.; Chouai, A.; Pellois, J.; Turro, C.; Dunbar, K. J. Am. Chem. Soc. 2009, 131, 11353–11360. 15. Aguirre, D.; Chitofides, H.; Angeles-Boza, A.; Chouai, A.; Turro, C.; Dunbar, K. Inorg. Chem. 2009, 48, 4435–4444. 16. Kang, M.; Chitofides, H.; Dunbar, K. Biochemistry 2008, 47, 2265–2276. 17. Deubel, D. J. Am. Chem. Soc. 2008, 130, 665–675. 18. Burda, J.; Gu, J. J. Inorg. Biochem. 2008, 102, 53–62. 19. Gómez, E.; Duddeck, H. Magn. Reson. Chem. 2009, 47, 222–227. 20. Hess, J. Thesis, Michigan State University, 1998. 21. Jaz´win´ski, J.; Rozwadowski, Z.; Magiera, D.; Duddeck, H. Magn. Reson. Chem. 2003, 41, 315–323. 22. Jaz´win´ski, J.; Duddeck, H. Magn. Reson. Chem. 2003, 41, 921–926. 23. Jaz´win´ski, J. J. Mol. Struct. 2005, 750, 7–17. 24. Jaz´win´ski, J. Tetrahedron: Asymmetry 2006, 17, 2358–2365. 25. Bocian, W.; Jaz´win´ski, J.; Sadlej, A. Magn. Reson. Chem. 2008, 46, 156–265. 26. Cmoch, P.; Jaz´win´ski, J. J. Mol. Struct. 2009, 919, 348–355. 27. Jaz´win´ski, J.; Sadlej, A. Tetrahedron: Asymmetry 2009, 20, 2331–2343. 28. Frelek, J.; Jaz´win´ski, J.; Masnyk, M.; Rus´kowska, P.; Szmigielski, R. Tetrahedron: Asymmetry 2005, 16, 2437–2448. 29. Frelek, J.; Górecki, M.; Jaz´win´ski, J.; Masnyk, M.; Rus´kowska, P.; Szmigielski, R. Tetrahedron: Asymmetry 2005, 16, 3188–3197. 30. Diaz Gómez, E.; Frelek, J.; Woz´nica, M.; Kowalska, P.; Jaz´win´ski, J.; Duddeck, H. Heterocycles 2007, 74, 357–367. 31. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A.; Vreven, T., Jr.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda. R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. GAUSSIAN 03, Revision B.5 GAUSSIAN, Inc.: Pittsburgh PA, 2003. 32. Rachele, J. J. Org. Chem. 1968, 28, 2889. 33. Kotha, S.; Behera, M.; Khedkar, P. Tetrahedron Lett. 2004, 45, 7589–7590. 34. Bose, A. Org. Synth. 1960, 40, 82. 35. Jeffs, P.; Yellin, B.; Mueller, M.; Heald, S. J. Org. Chem. 1988, 53, 471–477. 36. Wypchlo, K.; Duddeck, H. Tetrahedron: Asymmetry 1994, 5, 27–30.