Theoretical UV circular dichroism of aliphatic cyclic dipeptides

Four cyclic dipeptides (piperazine-2,5-diones), cyclo(L-Pro-Gly), cyclo(L-Pro-L-Leu), cyclo(L-Ala-L-Ala), and cyclo(L-Pro-L-Ala), were modeled from crystal structure data. Conformations resulting from energy minimization using molecular mechanics were compared with traditional ab initio and density functional theory geometric optimizations for each dipeptide. In all computational cases, the gas phase was assumed. The pi-pi transition feature of the UV circular dichroic (CD) spectra was predicted for each peptide structure via the classical dipole interaction model. The dipole interaction model predicted CD spectra that qualitatively agreed with experiment when MP2 or DFT geometries were used. By coupling MP2 or DFT geometric optimizations with the classical physics method of the dipole interaction model, significantly better CD spectra were calculated than those using geometries obtained by molecular mechanics. Thus, one can couple quantum mechanical geometries with a classical physics model for calculation of circular dichroism.     

Crown-ether-modified cyclic dipeptides as supramolecular chiral catalysts

With the objective to develop supramolecular catalysts for useful chemical transformations, we report here a rapid and efficient solid-phase synthesis of novel cyclic dipeptides (crown-CDPs) with a diversity of L-DOPA derived crown ether substituents and stereochemistry. We prepared and characterized 14 crown-CDPs and evaluated their efficiency as supramolecular epoxidation catalysts in a water/hexanes biphasic system. Yields increase significantly in the presence of the crown-CDPs, though enantioselectivity depends on the nature of the substituents. The results reported constitute a useful approach for chiral epoxides of interest and further illustrate the potential of cyclic peptides as supramolecular catalysts.     

Pmr characterization of diastereomeric forms of 6- and 7-membered cyclic compounds bearing two equivalent chiral atoms

meso and dl diastereomeric pairs of cyclic compounds with geminal probe groups in suitable position were analysed by PMR: anisochronism of diastereotopic probe protons was used for assignment of configuration; moreover, analysis of ring proton signals gave information on conformational features.     

The complex formation of calcium with aliphatic dipeptides

Dissociation constants for complexes of calcium with a series of dipeptides consisting of glycine, alanine, leucine and proline have been determined bypH-titrations. Two of these dissociation constants were checked by means of titration using a calcium sensitive electrode. The influence of the side chains on the stability of the complexes is discussed. Calcium forms only 1:1 complexes of the type CaLH⁺ (LH₂ = H₃ -CHR-CO-NH-CHR-COO^–) and probably also of the type CaLH ₂ ²⁺ . The two PMR signals of the non-equivalent methylene protons of glycylglycine were measured with and without the addition of calcium chloride at variouspH. On the basis of these results, possible structures of the complexes CaLH⁺ are postulated.

---

Komplexbildung von Calcium mit aliphatischen Dipeptiden

Zusammenfassung Für eine Reihe Reihe von Dipeptiden, bestehend aus den Aminosäuren Glycin, Alanin, Leucin und Prolin, wurden Dissoziationskonstanten für deren Calcium-Komplexe mit Hilfe vonpH-Titrationen bestimmt. Zwei dieser Dissoziationskonstanten wurden durch Messung mit einer Ca-sensitiven Elektrode überprüft. Der Einfluß der Seitenketten auf die Stabilität der Komplexe wird diskutiert. Calcium bildet nur 1:1 Komplexe der Form CaLH⁺ (LH₂=H₃ -CHR-CO-NH-CHR-COO^–) und vielleicht auch der Form CaLH ₂ ²⁺ . In einer H¹-NMR Untersuchung wurden die Signale der beiden nicht äquivalenten Methylengruppen von Glycylglycin gemessen, und zwar mit und ohne Zugabe von Calciumchlorid bei verschiedenstenpH-Werten. Auf Grund dieser Ergebnisse werden mögliche Strukturen für die Komplexe vorgeschlagen.

     

Quantum chemical study of cyclic dipeptides

The preferred conformations of cyclic dipeptides were first studied systemically using the density functional theory (DFT) B3LYP method at the 6‐31G(d) level. The structural characteristics of cyclic dipeptides were revealed, most of which have not been confirmed until now. Our studies showed that the six‐member main circles of cyclic dipeptides composed of natural L ‐amino acid residues appeared as boat conformations. The important factors that influence conformations of cyclic dipeptides, such as molecular total energy, nuclear repulsion energy, molecular orbit, spatial effects, and reactive mechanism, are discussed in detail. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Stereoselective interactions of chiral dipeptides on amylose based chiral stationary phases

Dipeptides are stereo-specifically involved in several biological functions that are challenging to separate enantiomerically. Elution order of enantiomers is an important issue in chiral chromatography. Amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase(CSP) is the best and most-widely-used CSP in chiral separations, but experimental data of enantiomeric separation of dipeptides on this CSP is lacking. Simulation studies were conducted to determine the order of elution and the chiral recognition mechanism of didpetides on this CSP. Results indicated that the docking energy of SR-enantiomers were higher than SS-antipodes. The range of docking energies for SR-enantiomers was -7.44 to -5.92 kcal/mol with CSP, but -7.15 to -5.87 kcal/mol for SS-stereoisomers. Therefore it is predicted that SS-enantiomer will elute first, followed by SR-antipode. Furthermore, hydrogen bondings, van der Waal’s interactions and electrostatic interactions were observed among SR- and SSenantiomers and chiral grooves of CSP. The number of hydrogen bonds was one in each enantiomer binding except S-Ala-R-Tyr, which contained two hydrogen bonds. No hydrogen bond was found in S-Ala-R-Trp, S-Leu-S-Trp, and S-Leu-S-Tyr dipeptides bindings. The chiral recognition mechanisms dictate different strengths of stereoselective bindings of the enantiomers on CSP.     

Synthesis and antimalarial evaluation of cyclic beta-amino acid-containing dipeptides

This paper describes an efficient synthesis and the antiparasitic evaluation of cyclic beta-amino acid-containing dipeptides 3.1-3.6 and 4.1-4.5. The antimalarial properties of all these dipeptides have been evaluated in vitro against Plasmodium falciparum and in vivo against Plasmodium berghai. Compounds 4.4 and 4.5 have been found to be very effective in this respect, with IC50 values of 3.87 and 3.64 microg/mL in the in vitro test, while 4.5 has also been found to be active in the in vivo evaluation.     

Oxidative cleavages of aliphatic and cyclic iodides

$\text{3}$ Undergoes elimination on treatment with m-chloroperbenzoic acid, performic acid or SO₂CI₂/NaOCI, while iodine is retained in the novel peracid dehydrogenation of $\text{9}$.     

Synthesis of mono N-trifluoroethylated cyclic dipeptides

Trifluoroethylated N-termini in linear dipeptides l-TyrXOR [X = Gly, d-Ala, l-Leu, l-Phe, and l-Glu; R = H, Me, Et] exhibit sufficient nucleophilicity to give piperazine-2,5-dione ring formation through intramolecular cyclization reaction in acidic aqueous solutions. The reactions occur in high yield and with absolute configuration retention.     

Hindered rotation in five-membered cyclic nitrosamines: A 13C NMR study

The equilibrium rotamer populations and N? N rotational barriers of N-nitrosopyrrolidine (1), N-nitrosothiazolidine (2), N-nitrosooxazolidine (3) and their 2-methyl derivatives, 4, 5 and 6, were determined by ¹³C NMR spectroscopy. While equal rotamer populations occur in 1 and 2, the E rotamers predominate in the other four compounds, with the highest percentage (92%) of E rotamer occurring in N-nitroso-2-methyloxazolidine (6). The average barrier to N? N bond rotation varies over a range of 4.1 kcal mol^?1in these compounds, decreasing in the order N-nitrosopyrrolidine > N-nitrosothiazolidine > N-nitrosooxazolidine. The compounds which contain an exocyclic 2-methyl group have average rotational barriers which are 0.1–0.9 kcal mol^?1 higher than those of the corresponding unmethylated derivatives. The results are interpreted in terms of the relative effects of steric hindrance by the 2-methyl substituents and electron induction by the heterocyclic sulfur and oxygen atoms on both the rotamer populations and the N? N rotational barriers.     

Synthesis and properties of cyclic diester based aliphatic copolyesters

Melt polycondensation was used to prepare a systematic series of random and amorphous copolyesters using the following cycloaliphatic diesters: dimethyl‐1,4‐cyclohexane dicarboxylate (DMCD), dimethyl bicyclo[2.2.1]heptane‐1,4‐dicarboxylate (DMCD‐1), dimethyl bicyclo[2.2.2]octane‐1,4‐dicarboxylate (DMCD‐2), dimethyl bicyclo[3.2.2]nonane‐1,5‐dicarboxylate (DMCD‐3), 1,4‐dimethoxycarbonyl‐1,4‐dimethylcyclohexane (DMCD‐M) and the aliphatic diols: ethylene glycol (EG) and 1,4‐cyclohexane dimethanol (CHDM). The polymer compositions were determined by nuclear magnetic resonance (NMR) and the molecular weights were determined using size exclusion chromatography (SEC). The polyesters were characterized by dynamic mechanical analysis (DMA), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The copolyester based on DMCD‐2 was observed to have a higher glass transition temperature (T_g up to 115 °C) than the other copolyesters of this study. For poly[x(DMCD‐2)y(DMCD) 30(EG)70(CHDM)], T_g increases linearly with increase of DMCD‐2 mole content. DMA showed that all of the cycloaliphatic copolyesters have secondary relaxations, resulting from the conformational transitions of the cyclohexylene rings. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2162–2169, 2010     

Fragmentation of deprotonated cyclic dipeptides by electrospray ionization mass spectrometry

The fragmentation pathways of deprotonated cyclic dipeptides have been studied by electrospray ionization multi‐stage mass spectrometry (ESI‐MSⁿ) in negative mode. The results showed that the fragmentation pathways of deprotonated cyclic dipeptides depended significantly on the different substituents, the side chains of amino acid residues at the diketopiperazine ring. In the spectra of deprotonated cyclic dipeptides, the ion [M? H? substituent radical]^? was firstly observed in the ESI mode. The characteristic fragment ions [M? H? substituent radical]^? and [M? H? (substituent? H)]^? could be used as the symbols of particular cyclic dipeptides. The hydrogen/deuterium (H/D) exchange experiment, the high‐resolution mass spectrometry (Q‐TOF) and theoretical calculations were used to rationalize the proposed fragmentation pathways and to verify the differences between the fragmentation pathways. The relative Gibbs free energies (ΔG) of the product ions and possible fragmentation pathways were estimated using the B3LYP/6–31++G(d, p) model. The results have some potential applications in the structural elucidation and interpretation of the mass spectra of homologous compounds and will enrich the gas‐phase ESI‐MS ion chemistry of cyclic dipeptides. Copyright © 2009 John Wiley & Sons, Ltd.     

Enthalpic characteristics of solution of amino acids and aliphatic dipeptides in aqueous solutions of KCl

The integral enthalpies of dissolution Δ_sol H ^m of L-α-serine and L-α-asparagine in mixtures of water with KCl were measured in electrolyte concentrations of up to 4 mol/kg at 298.15 K. The standard enthalpies of dissolution (Δ_sol H ^o) and transfer (Δ_tr H ^o) of amino acids from water to aqueous solutions of KCl were calculated. The enthalpic pair interaction coefficients h _xy of biomolecules with KCl were estimated within the McMillan-Mayer theory. The changing nature of the interaction between the components of the solution (depending on the structure of the dissolved biosubstance side substituents) is shown on the basis of data we obtained earlier for amino acids and dipeptides series. Estimates of the contributions from the electrostatic and other interactions of dipolar ions of amino acids and dipeptides with ions of electrolyte KCl in the enthalpic pair interaction coefficients h _xy are obtained using the Kirkwood approach.     

Pmr characterization of diastereomeric forms of acyclic compounds bearing two equivalent chiral atoms in 1,5-positions

Assignment of configurations to diastereomeric pairs was based on anisochronism of diastereotopic protons of suitable probe groups, at various distances from both chiral centers.