Jari Tamminen

Bile Acids as Building Blocks of Supramolecular Hosts

A review of the use of bile acid-based compounds as building blocks for designing novel supramolecular hosts for molecular recognition is presented. Pharmacological applications and the newest spectroscopic and computational studies of bile acid derivatives are also shortly considered.

1H-, 13C-, and 15N-NMR and ESI-TOF+ MS studies of a supramolecular complex of silver(I) and a cholaphane

A novel application of the mixed anhydride procedure for synthesising lithocholic acid piperazine diamide, an important intermediate in designing bile acid-based supramolecular host molecules, is reported. The synthesis of a thiophene-containing cholaphane with transition metal complexation ability and 1H-, 13C-, and 15N-NMR as well as ESI-TOF+ MS spectral characterisation of the ligand and its Ag(I) complex are included. The coordination of the Ag(I) ion as well as an ability of the cholaphane to recognise Ag(I) ion over alkali metal ions, especially potassium ion, is discussed. The possible medical applications are also presented.

Comparison of calculated DFT/B3LYP and experimental 13C and 17O NMR chemical shifts, ab initio HF/6-31G* optimised structures, and single crystal X-ray structures of some substituted methyl 5β-cholan-24-oates

Abstract Single crystal X-ray structures (monoclinic space group P2 1 ) for methyl 3-oxo-5β-cholan-24-oate and methyl 3,12-dioxo-5β-cholan-24-oate have been solved and compared with HF/6-31G* optimised structures. In the crystalline packings the side chains are connected with weak OC(sp 3 ) H ⋯ O -type of interactions between C25– H and C24– O –C25 and the keto ends with weak C(sp 3 ) H ⋯ O C-type of interactions between C4– H and O C3. The orientations of the side chains, which steric configurations are of great importance to the biological activity of the molecules, are compared with the experimental structure of methyl 3α-hydroxy-5β-cholan-24-oate. Probable reasons for the observed differences are discussed. In addition, 13 C and 17 O NMR chemical shifts of methyl 3-oxo-5β-cholan-24-oate and methyl 3,12-dioxo-5β-cholan-24-oate as well as the epimeric methyl 3α-hydroxy-5β-cholan-24-oate and methyl 3β-hydroxy-5β-cholan-24-oate have been calculated (DFT/B3LYP/6-311G*) and compared with the experimental values by linear regression analyses. In general, the correspondence between the theoretical and experimental parameters is good or excellent.

Comparison of epimeric methyl lithocholate and methyl iso-lithocholate molecules: single crystal X-ray structure of methyl lithocholate, ab initio HF/6-31G* optimized structures and experimental and calculated DFT/B3LYP 13C NMR chemical shifts

Abstract 13 C NMR chemical shifts have been measured and assigned for epimeric methyl 3α/β-hydroxy-5β-cholan-24-oates (methyl lithocholate [3α-OH epimer] and methyl iso-lithocholate [3β-OH epimer]). Their molecular dynamics simulations suggest that for both epimers there exists two predominant gas phase conformations, which have been further forwarded for ab initio/HF optimizations and DFT/GIAO based 13 C NMR chemical shift calculations. Excellent linear relationships have been observed between experimental and calculated 13 C NMR chemical shifts for both epimers. For methyl lithocholate (MeLC), the other minimum energy conformation equates very well with the single crystal X-ray structure (orthorhombic, space group P 2 1 2 1 2 1 , unit cell a=7.14710(10) A , b=11.9912(2) A , c=26.4368(5) A ). The crystalline packing of MeLC consists of continuous parallel intermolecular hydrogen bonded [3α-O H ⋯ O C24] head-to-tail polymeric chains, which are further cross-linked by many simultaneous weak C(sp 3 ) H ⋯ O -type of interactions.

Macrocycles prepared from lithocholic acid, piperazine and isomeric pyridine dicarboxylic acids and their selective affinities towards sodium and potassium

Abstract Two novel macrocycles prepared from lithocholic acid, piperazine and pyridine dicarboxylic acids (2,6- and 3,5-isomers), have been characterized by 13C NMR and ESI–MS techniques. In case of the pyridine-2,6-dicarboxylate derivative, the molecular formula of the cycle was C59H87O6N3 (I), while the pyridine-3,5-dicarboxylate derivative (II) was a trimeric structure by molecular mass when compared with I. Furthermore, cycle I showed a special affinity towards potassium cation, while II possessed significant proton and sodium cation recognition properties.

3α,3′α-Bis(n-acetoxyphenylcarboxy)-5β-cholan-24-oic acid ethane-1,2-diol diesters (n = 2-4):13C NMR chemical shifts, variable-temperature and NOE1H NMR measurements and MO calculations of novel bile acid-based dimers

Three novel bile acid‐based molecular dimers, 3α,3′α‐bis(n‐acetoxyphenylcarboxy)‐5β‐cholan‐24‐oic acid ethane‐1,2‐diol diesters (n = 2–4), 1–3, were synthesized from lithocholic acid (3α‐hydroxy‐5β‐cholan‐24‐oic acid) ethane‐1,2‐diol diester and isomeric n‐acetoxybenzoyl chlorides (n = 2–4). Their cleft type conformational preferences were suggested theoretically by PM3 molecular orbital calculations. Molecular weights determined by the matrix‐assisted laser desorption/ionization time‐of‐flight technique and 13C NMR chemical shifts of the 1–3 are also presented. Copyright

13C, 15N and 113Cd NMR and Molecular Orbital Studies of Novel Bile Acid N-(2-aminoethyl)amides and Their Cd2+-complexes

Lithocholic acid N-(2-aminoethyl)amide (1) and deoxycholic acid N-(2-aminoethyl)amide(2) have been prepared and characterized by1H, 13C and 15N NMR. The accurate molecular masses of 1 and 2 have been determined by ESI MS. The formation of the Cd2+-complexes (1+Cd and 2+Cd) in CD3OD solution have been detected by 1H,13C, 15N and 113Cd NMR. The 13C NMR chemical shift assignments of 1 and 2 and their Cd2+-complexes are based on DEPT-135 and z-GS 1H,13C HMQC experiments as well as comparison with the assignments of the related structures. The 15N NMR chemical shiftassignments of the ligands and theirCd2+-complexes are based on z-GS1H,15N HMBC experiments. 13C NMR chemical shift differences between 1and its 1:1 Cd2+-complex based on ab initiocalculations at Hartree-Fock SCI-PCM level using3-21G(d) basis set are in agreement with theexperimental shift changes observed onCd2+-complexation.

Synthesis, 1 H, 13 C, 15 N, and 113 Cd NMR, ESI-TOF MS, Semiempirical MO (PM3), ab initio/HF and Cation/Anion Binding Studies of N-deoxycholyl-L-tryptophan

The synthesis, structural characterization, and cation/anion binding properties ofa new bile acid-amino acid conjugate, N-deoxycholyl-l-tryptophan, aredescribed. The structures of the ligand and its cadmium adduct at different pHconditions and various cadmium perchlorate concentrations were determined bymodern multinuclear magnetic resonance spectroscopic as well as ESI-TOF MStechniques. Also semiempirical PM3 and ab initio/HF molecular modellingstudies were performed. Based on 1H,1H NOESY measurementsN-deoxycholyl-l-tryptophan in alkaline conditions was found to appearin a bent conformation which was clearly different from the conformations in neutraland acidic solutions. According to molecular modelling in its minimum energy structurethe tryptophan backbone of the ligand was folded close to the deoxycholic acid skeletonand the structure was stabilized by an intramolecular hydrogen bond. The multinuclearmagnetic resonance experiments indicated that Cd2+-cation was bound with theligand in neutral and alkaline conditions while in acidic conditions protons block thebinding site. ESI-TOF MS revealed clearly a competition between sodium and cadmiumions, the ligand having a stronger affinity for sodium. Cadmium binding occurred onlywhen excess of cadmium was used. Further, ESI-TOF MS spectra showed that variouschlorine oxyanions originated from perchlorate anion formed together with cationsdifferent adducts with the ligand.

13C NMR spectral assignments of 3α,3′α‐bis(arylcarboxy)‐5β‐cholan‐24‐oic acid ethane‐1,2‐diol diesters: new lithocholic acid‐based molecular clefts

3α,3′α‐Bis(arylcarboxy)‐5β‐cholan‐24‐oic acid ethane‐1,2‐diol diesters (1–3) were synthesized by the reaction of an aroyl chloride (aroyl=2,6‐dichlorobenzoyl, 2‐naphthoyl and 1‐pyrenoyl) with lithocholic acid (3α‐hydroxy‐5β‐cholan‐24‐oic acid) ethane‐1,2‐diol diester. The 13C NMR chemical shift assignments of the formed molecular clefts 1–3, pyrene‐1‐carboxylic acid methyl ester (4) (used as model compound) and 1‐pyrenoyl chloride (5) are based on literature data and 13C DEPT‐135, 1H,13C HMQC and 1H,13C HMBC experiments. The molecular weights of 1–3 were determined by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. Copyright