Synthesis, 18F-labelling and radiopharmacological characterisation of the C-terminal 30mer of Clostridium perfringens enterotoxin as a potential claudin-targeting peptide.

The cell surface receptor claudin-4 (Cld-4) is upregulated in various tumours and represents an important emerging target for both diagnosis and treatment of solid tumours of epithelial origin. The C-terminal fragment of the Clostridium perfringens enterotoxin cCPE290-319 appears as a suitable ligand for targeting Cld-4. The synthesis of this 30mer peptide was attempted via several approaches, which has revealed sequential SPPS using three pseudoproline dipeptide building blocks to be the most efficient one. Labelling with fluorine-18 was achieved on solid phase using N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) and 4-[18F]fluorobenzoyl chloride as 18F-acylating agents, which was the most advantageous when [18F]SFB was reacted with the resin-bound 30mer containing an N-terminal 6-aminohexanoic spacer. Binding to Cld-4 was demonstrated via surface plasmon resonance using a protein construct containing both extracellular loops of Cld-4. In addition, cell binding experiments were performed for 18F-labelled cCPE290-319 with the Cld-4 expressing tumour cell lines HT-29 and A431 that were complemented by fluorescence microscopy studies using the corresponding fluorescein isothiocyanate-conjugated peptide. The 30mer peptide proved to be sufficiently stable in blood plasma. Studying the in vivo behaviour of 18F-labelled cCPE290-319 in healthy mice and rats by dynamic PET imaging and radiometabolite analyses has revealed that the peptide is subject to substantial liver uptake and rapid metabolic degradation in vivo, which limits its suitability as imaging probe for tumour-associated Cld-4.

Bilirubin, model membranes and serum albumin interaction: The influence of fatty acids.

Electronic circular dichroism (ECD), absorption and fluorescence spectroscopy were used to study the enantioselective interactions which involved bilirubin (BR), liposomes, human serum albumin of two different purities, pure (HSA) and non-purified of fatty acids (FA-HSA), and individual fatty acids. The application of the ECD technique to such a complex problem provided a new perspective on the BR binding to liposomes. Our results demonstrated that in the presence of pure HSA, BR preferred to bind to the protein over the liposomes. However, in the presence of FA-HSA, BR significantly bound to the liposomes composed either of DMPC or of sphingomyelin and bound only moderately to the primary and secondary binding sites of FA-HSA even at high BR concentrations. For the DMPC liposomes, even a change of BR conformation upon binding to the primary binding site was observed. The individual saturated fatty acids influenced the BR binding to HSA and liposomes in a similar way as fatty acids from FA-HSA. The unsaturated fatty acids interacted with BR alone and prevented it from interacting with either 99-HSA or the liposomes. In the presence of arachidonic acid, BR interacted enantioselectively with the liposomes and only moderately with 99-HSA. Hence, our results show a substantial impact of the liposomes on the BR binding to HSA. As a consequence of the existence of fatty acids in the blood plasma and in the natural structure of HSA, BR may possibly bind to the cell membranes even though it is normally bound to HSA.

Isoquinoline Alkaloids from Fumaria officinalis L. and Their Biological Activities Related to Alzheimer's Disease.

Two new isoquinoline alkaloids, named fumaranine (2) and fumarostrejdine (10), along with 18 known alkaloids were isolated from aerial parts of Fumaria officinalis. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses and by comparison with literature data. The absolute configuration of the new compound 2 was determined by comparing its circular dichroism spectra with those of known analogs. Compounds isolated in sufficient amounts were evaluated for their acetylcholinesterase, butyrylcholinesterase, prolyl oligopeptidase (POP), and glycogen synthase kinase-3ß inhibitory activities. Parfumidine (8) and sinactine (15) exhibited potent POP inhibition activities (IC50 99±5 and 53±2 µM, resp.).

Mutual structural effect of bilirubin and model membranes by vibrational circular dichroism.

In this study, vibrational circular dichroism (VCD) spectroscopy was employed for the first time to study the bilirubin (BR) interaction with model membranes and models for membrane proteins. An enantioselective interaction of BR with zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and sphingomyelin (SPM) liposomes was observed by VCD and electronic circular dichroism (ECD) complemented by absorption and fluorescence spectroscopy. The M-form of BR was preferentially recognized in the BR/DMPC system at concentration above 1×10(-4)M, for lower concentrations the P-form of BR was recognized by the DMPC liposomes. The VCD spectra also showed that the SPM liposomes, which represent the main component of nerve cell membrane, were significantly more disturbed by the presence of BR than the DMPC liposomes-a stable association with a strong VCD signal was observed providing the explanations for the supposed BR neurotoxicity. The effect of time and pH on the BR/DMPC or SPM liposome systems was shown to be essential while the effect of temperature in the range of 15-70°C was negligible demonstrating the surprisingly high temperature stability of BR when interacting with the studied membranes. The influence of a membrane protein was tested on a model consisting of poly-l-arginine (PLAG) bound in the α-helical form to the surface of 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol) liposomes and sodium dodecyl sulfate micelles. VCD and also ECD spectra showed that a variety of BR diastereoisomers interacted with PLAG in such systems. In a system of PLAG with micelles composed of sodium dodecyl sulfate, the M-form of bound BR was observed.

Comparison of the electronic and vibrational optical activity of a europium(III) complex.

The geometry and the electronic structure of chiral lanthanide(III) complexes are traditionally probed by electronic methods, such as circularly polarised luminescence (CPL) and electronic circular dichroism (ECD) spectroscopy. The vibrational phenomena are much weaker. In the present study, however, significant enhancements of vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectral intensities were observed during the formation of a chiral bipyridine-Eu(III) complex. The ten-fold enhancement of the vibrational absorption and VCD intensities was explained by a charge-transfer process and the dominant effect of the nitrate ion on the spectra. A much larger enhancement of the ROA and Raman intensities and a hundred-fold increase of the circular intensity difference (CID) ratio were explained by the resonance of the λ = 532 nm laser light with the (7)F0 → (5)D0 transitions. This phenomenon is combined with a chirality transfer, and mixing of the Raman and luminescence effects involving low-energy (7)F states of europium. The results thus indicate that the vibrational optical activity (VOA) may be a very sensitive tool for chirality detection and probing of the electronic structure of Eu(III) and other coordination compounds.

Photo-isomerization and oxidation of bilirubin in mammals is dependent on albumin binding.

The bilirubin (BR) photo-conversion in the human body is a protein-dependent process; an effective photo-isomerization of the potentially neurotoxic Z,Z-BR as well as its oxidation to biliverdin in the antioxidant redox cycle is possible only when BR is bound on serum albumin. We present a novel analytical concept in the study of linear tetrapyrroles metabolic processes based on an in-depth mapping of binding sites in the structure of human serum albumin (HSA). A combination of fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and molecular modeling methods was used for recognition of the binding site for BR, its derivatives (mesobilirubin and bilirubin ditaurate), and the products of the photo-isomerization and oxidation (lumirubin, biliverdin, and xanthobilirubic acid) on HSA. The CD spectra and fluorescent quenching of the Trp-HSA were used to calculate the binding constants. The results of the CD displacement experiments performed with hemin were interpreted together with the findings of molecular docking performed on the pigment-HSA complexes. We estimated that Z,Z-BR and its metabolic products bind on two independent binding sites. Our findings support the existence of a reversible antioxidant redox cycle for BR and explain an additional pathway of the photo-isomerization process (increase of HSA binding capacity; the excess free [unbound] BR can be converted and also bound to HSA).

Cyclopeptides containing the DEKS motif as conformationally restricted collagen telopeptide analogues: synthesis and conformational analysis.

The collagen telopeptides play an important role for lysyl oxidase-mediated crosslinking, a process which is deregulated during tumour progression. The DEKS motif which is located within the N-terminal telopeptide of the α1 chain of type I collagen has been suggested to adopt a ßI-turn conformation upon docking to its triple-helical receptor domain, which seems to be critical for lysyl oxidase-catalysed deamination and subsequent crosslinking by Schiff-base formation. Herein, the design and synthesis of cyclic peptides which constrain the DEKS sequence in a ß-turn conformation will be described. Lysine-side chain attachment to 2-chlorotrityl chloride-modified polystyrene resin followed by microwave-assisted solid-phase peptide synthesis and on-resin cyclisation allowed for an efficient access to head-to-tail cyclised DEKS-derived cyclic penta- and hexapeptides. An N(ε)-(4-fluorobenzoyl)lysine residue was included in the cyclopeptides to allow their potential radiolabelling with fluorine-18 for PET imaging of lysyl oxidase. Conformational analysis by (1)H NMR and chiroptical (electronic and vibrational CD) spectroscopy together with MD simulations demonstrated that the concomitant incorporation of a D-proline and an additional lysine for potential radiolabel attachment accounts for a reliable induction of the desired ßI-turn structure in the DEKS motif in both DMSO and water as solvents. The stabilised conformation of the cyclohexapeptide is further reflected by its resistance to trypsin-mediated degradation. In addition, the deaminated analogue containing allysine in place of lysine has been synthesised via the corresponding ε-hydroxynorleucine containing cyclohexapeptide. Both ε-hydroxynorleucine and allysine containing cyclic hexapeptides have been subjected to conformational analysis in the same manner as the lysine-based parent structure. Thus, both a conformationally restricted lysyl oxidase substrate and product have been synthetically accessed, which will enable their potential use for molecular imaging of these important enzymes.

A Solid Phase Vibrational Circular Dichroism Study of Polypeptide-Surfactant Interaction.

We studied the interaction of poly-l-lysine (PLL) and poly-l-arginine (PLAG) with sodium dodecyl sulfate (SDS) surfactant and the interaction of poly-l-glutamic acid (PLGA) and poly-l-aspartic acid (PLAA) with tetradecyltrimethylammonium bromide (TTAB) surfactant using vibrational circular dichroism (VCD) spectroscopy in the region of C-H stretching vibration and in the Amide I region both in solution and in mulls. A chirality transfer from polypeptides to achiral surfactants was observed in the C-H stretching region, where measurements in solution were impossible. This observation was enabled by a special sample treatment technique using lyophilization and the preparation of mulls. This technique demonstrated itself as an interesting and beneficial tool for VCD measurements. In addition, we observed that SDS changed the secondary structure of PLL to the ß-sheet and of PLAG to the α-helix. TTAB disrupted the PLGA and PLAA structure. These results were obtained in the mull but were confirmed by the VCD spectra measured in solution and by electronic circular dichroism. The chirality transfer from the polypeptides to SDS was caused by polypeptides ordered into a specific conformation during the interaction, while in the TTBA system it was induced primarily by the chirality of the amino acid residues.

Insight into the structural and biological relevance of the T/R transition of the N-terminus of the B-chain in human insulin.

The N-terminus of the B-chain of insulin may adopt two alternative conformations designated as the T- and R-states. Despite the recent structural insight into insulin-insulin receptor (IR) complexes, the physiological relevance of the T/R transition is still unclear. Hence, this study focused on the rational design, synthesis, and characterization of human insulin analogues structurally locked in expected R- or T-states. Sites B3, B5, and B8, capable of affecting the conformation of the N-terminus of the B-chain, were subjects of rational substitutions with amino acids with specific allowed and disallowed dihedral φ and ψ main-chain angles. α-Aminoisobutyric acid was systematically incorporated into positions B3, B5, and B8 for stabilization of the R-state, and N-methylalanine and d-proline amino acids were introduced at position B8 for stabilization of the T-state. IR affinities of the analogues were compared and correlated with their T/R transition ability and analyzed against their crystal and nuclear magnetic resonance structures. Our data revealed that (i) the T-like state is indeed important for the folding efficiency of (pro)insulin, (ii) the R-state is most probably incompatible with an active form of insulin, (iii) the R-state cannot be induced or stabilized by a single substitution at a specific site, and (iv) the B1-B8 segment is capable of folding into a variety of low-affinity T-like states. Therefore, we conclude that the active conformation of the N-terminus of the B-chain must be different from the "classical" T-state and that a substantial flexibility of the B1-B8 segment, where GlyB8 plays a key role, is a crucial prerequisite for an efficient insulin-IR interaction.

Preparation and enantioselectivity binding studies of a new chiral cobalt(II)porphyrin-Tröger's base conjugate.

A new bis[cobalt(II)porphyrin]-Tröger's base conjugate was studied as a potential receptor for methyl esters of several amino acids. The conjugate was prepared as racemate, and then resolved via preparative high-performance liquid chromatography (HPLC) on a chiral column. The high affinity to lysine, histidine, and proline methyl esters was found by complexation studies followed by UV-Vis spectroscopy. The studies of pure enantiomers, followed by UV-Vis and electronic circular dichroism spectroscopy, revealed the highest enantioselectivity for lysine methyl ester.

Determination of absolute configuration and conformation of a cyclic dipeptide by NMR and chiral spectroscopic methods.

Increasing precision of contemporary computational methods makes spectroscopies such as vibrational (VCD) and electronic (ECD) circular dichroism attractive for determination of absolute configurations (AC) of organic compounds. This is, however, difficult for polar, flexible molecules with multiple chiral centers. Typically, a combination of several methods provides the best picture of molecular behavior. As a test case, all possible stereoisomers with known AC (RS, SR, SS, and RR) of the cyclic dipeptide cyclo(Arg-Trp) (CAT) were synthesized, and the performances of the ECD, infrared (IR), VCD, Raman, Raman optical activity (ROA), and nuclear magnetic resonance (NMR) techniques for AC determination were investigated. The spectra were interpreted with the aid of density functional theory (DFT) calculations. Folded geometries stabilized by van der Waals and electrostatic interactions between the diketopiperazine (DKP) ring and the indole group are predicted to be preferred for CAT, with more pronounced folding due to Arg-Trp stacking in the case of SS/RR-CAT. The RS/SR isomers prefer a twist-boat puckering of the DKP ring, which is relatively independent of the orientation of the side chains. Calculated conformer-averaged VCD and ECD spectra explain most of the experimentally observed bands and allow for AC determination of the tryptophan side-chain, whereas the stereochemical configuration of the arginine side-chain is visible only in VCD. NMR studies provide characteristic long-range (2)J(C,H) and (3)J(C,H) coupling constants, and nuclear Overhauser effect (NOE) correlations, which in combination with either ECD or VCD also allow for complete AC determination of CAT.

Chiroptical properties of bilirubin-serum albumin binding sites.

Although the interactions between bilirubin and serum albumin are among the most studied serum albumin-ligand interactions, the binding-site location and the participation of bilirubin-serum albumin complexes in pathological and physiological processes are under debate. In this article, we have benefited from the chiral structure of bilirubin and used CD spectroscopy to characterize the structure of bilirubin bound to human and bovine serum albumins. We determined that in a phosphate buffer at pH 7.8 there are three binding sites in both human and bovine serum albumins. While the primary binding sites in human and bovine serum albumins bind bilirubin with P- and M-helical conformations, respectively, the secondary binding sites in both albumins bind bilirubin in the P-helical conformation. We have shown that the bonding of bilirubin to the serum albumin matrix is a more favorable process than the self-association of bilirubin under the studied conditions, with a maximum of three bound bilirubins per serum albumin molecule. Although bilirubin bound to the primary binding site has attracted the most attention, the presented results have documented the impact of the secondary binding sites which are relevant in the displacement reactions between BR and drugs and in the phenomena where bilirubin plays antioxidant, antimutagenic, and anti-inflammatory roles.

Vibrational circular dichroism study of polypeptide model-membrane systems.

In this article, we describe the mutual structural effect of the interaction between the model membranes and polylysine and poly-l-arginine. Vibrational circular dichroism (VCD), a method exceptionally sensitive to the polypeptide structure that has not been established in such studies before, was the primary method of this study. A complementary technique, electronic circular dichroism, was applied to verify the newly obtained results and as a bridge to the previous studies. We used micelles composed of sodium dodecyl sulfate (SDS) as a monolayer membrane model and large unilamellar vesicles composed of phospholipids as a bilayer membrane model. We describe the conformational changes of the polypeptides caused by the interaction with the model membranes. Among others, the presence of the liposomes in the solution generated special conditions for the formation of the α-helical structure of poly-l-arginine; the presence of SDS induced the formation of the ß-structure of polylysine. From a methodological point of view, we emphasize the advantages of infrared spectroscopic techniques for the liposomic membrane studies as well as the preference of ultraviolet techniques for smaller micellar systems.

Determining the absolute configuration of two marine compounds using vibrational chiroptical spectroscopy.

Chiroptical techniques are increasingly employed for assigning the absolute configuration of chiral molecules through comparison of experimental spectra with theoretical predictions. For assignment of natural products, electronic chiroptical spectroscopies such as electronic circular dichroism (ECD) are routinely applied. However, the sensitivity of electronic spectral parameters to experimental conditions and the theoretical methods employed can lead to incorrect assignments. Vibrational chiroptical methods (vibrational circular dichroism, VCD, and Raman optical activity, ROA) provide more reliable assignments, although they, in particular ROA, have been little explored for assignments of natural products. In this study, the ECD, VCD, and ROA chiroptical spectroscopies are evaluated for the assignment of the absolute configuration of a highly flexible natural compound with two stereocenters and an asymmetrically substituted double bond, the marine antibiotic Synoxazolidinone A (SynOxA), recently isolated from the sub-Arctic ascidian Synoicum pulmonaria. Conformationally averaged nuclear magnetic resonance (NMR), ECD, Raman, ROA, infrared (IR) and VCD spectral parameters are computed for the eight possible stereoisomers of SynOxA and compared to experimental results. In contrast to previously reported results, the stereochemical assignment of SynOxA based on ECD spectral bands is found to be unreliable. On the other hand, ROA spectra allow for a reliable determination of the configuration at the double bond and the ring stereocenter. However, ROA is not able to resolve the chlorine-substituted stereogenic center on the guanidinium side chain of SynOxA. Application of the third chiroptical method, VCD, indicates unique spectral features for all eight SynOxA isomers in the theoretical spectra. Although the experimental VCD is weak and restricted by the limited amount of sample, it allows for a tentative assignment of the elusive chlorine-substituted stereocenter. VCD chiroptical analysis of a SynOxA derivative with three stereocenters, SynOxC, results in the same absolute configuration as for SynOxA. Despite the experimental challenges, the results convincingly prove that the assignment of absolute configuration based on vibrational chiroptical methods is more reliable than for ECD.

Stacked and continuous helical self-assemblies of guanosine monophosphates detected by vibrational circular dichroism.

The aim of this study was to characterize self-assembled structures of guanosine derivatives in aqueous solutions by vibrational circular dichroism (VCD) and electronic circular dichroism (ECD). Three guanosine derivatives were studied [5'-guanosine monophosphate (GMP), diphosphate (GDP), and triphosphate (GTP)] using a broad range of concentrations and various metal/guanosine ratios. VCD was used for the first time in this field and showed itself to be a powerful method for obtaining specific structural information in solution. It can also help to determine the impact that the cations have, when added to the solution, on the versatile structures of guanine derivatives in terms of their association and disassociation. Based on the markedly different intensities and signs of the VCD signals observed for different concentrations of guanosine derivatives, we propose various structures based on guanine quartets for high guanosine concentrations and high K(+)/guanosine ratios (i.e., columnar helical organization of the quartets, which are rearranged into a continuous helix). We performed a degenerate coupled oscillator (DCO) calculation to interpret the VCD spectra obtained and how they vary during the assembly of guanosine derivatives. The calculations correctly predicted the VCD spectra and enabled us to identify the structures of the metal cation/guanosine monophosphate aggregates. ECD in the ultraviolet region was used as a diagnostic tool to characterize the studied systems and as a contact point between the previously defined structures of the guanine derivative assemblies and the molecular systems studied here. These studies revealed that the VCD technique is a powerful new method for determining the structures of optically active guanosine motifs.

Absolute configuration of a cyclic dipeptide reflected in vibrational optical activity: ab initio and experimental investigation.

The ability of Raman optical activity (ROA) and vibrational circular dichroism (VCD) experiments to determine the absolute configuration of chiral molecules with multiple stereogenic centers was explored for four diastereoisomers of a conformationally flexible cyclic dipeptide, cyclo(Arg-Tyr(OMe)). The reliability of the interpretation depended on the correct description of the molecular conformation, which was found to be strongly affected by intramolecular interactions. In particular, when dispersion corrections were included in the density functional theory calculations, the simulated spectra matched the experimental observations well. Experimental and theoretical ROA and VCD spectra were well correlated for all the absolute configurations (RS, SR, SS, and RR) of protonated cyclo(Arg-Tyr(OMe)). These spectroscopies thus appear useful not only for reliable determination of the absolute configuration and conformation but also in revealing the role of hydrogen bonds and C-H···π interactions in the structure stabilization, which can potentially be used when designing enzyme inhibitors and supramolecular architectures.

Supramolecular arrangement of guanosine/5-guanosine monophosphate binary mixtures studied by methods of circular dichroism.

Self-assembly of molecules is one of the fundamental processes in biology and in supramolecular chemistry. Guanosine (Guo) and its derivatives are among the widely studied molecules because of self-assembly abilities. Their tetrameric associates are the nature of telomeric DNA, and furthermore they are fundamental building blocks of supramolecular reversible gels, which may arise in certain physical and chemical conditions. Although poorly soluble in water, Guo forms interesting structures with guanosine 5'-monophosphate salt (GMP) in the TRIS buffer. We used electronic circular dichroism and vibrational circular dichroism to describe the thermal response of gels formed by the Guo/GMP binary mixture. Using these complementary techniques suitable to study conformational changes of chiral compounds, we obtained information about the involvement of functional groups and weak interactions in the guanosine quartet (G(4)) and stacked G(4) structures.

Study of stereoselective interactions of carbamoylated quinine and quinidine with 3,5-dinitrobenzoyl α-amino acids using VCD spectroscopy in the region of C−H stretching vibrations.

The stereoselective complexation of tert-butylcarbamoyl quinine and tert-butylcarbamoyl quinidine selectors (SOs) with 3,5-dinitrobenzoyl (DNB) derivatives of D- and L-alpha amino acids (DNB-Ala, DNB-Val, DNB-Leu, and DNB-Ile) as well as achiral DNB-Gly has been studied by vibrational circular dichroism (VCD) spectroscopy in the spectral region of C−H stretching vibrations. All the complexes of SOs and sterically compatible enantiomers of derivatized amino acid selectands (SAs) showed induced circular dichroism (ICD) bands in the region of aromatic C−H stretching vibrations, indicating the occurrence of a π-π interaction between the aromatic moieties of SA and SO. To our knowledge, this is the first report in which a π-π interaction was observed by VCD spectroscopy in this spectral region. No ICD bands were disclosed in the spectra of the sterically incompatible SA and SO complexes. The spectral pattern in the region of aliphatic C−H stretching vibrations showed interaction-induced conformational adaptations in sterically favorable SA and SO complexes. No such spectral changes were observed for any of the sterically incompatible complexes. The DNB-Gly complexes exhibited spectral patterns similar to those observed for sterically favorable pairs of SOs and chiral SAs.

Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid-base behavior with unconjugated bilirubin.

Unconjugated bilirubin (UCB) is the end-product of heme catabolism in the intravascular compartment. Although beneficial for human health when mildly elevated in the body, when present at greater than a critical threshold concentration, UCB exerts toxic effects that are related to its physico-chemical properties, particularly affecting the central nervous system. The aim of the present study was to characterize bilirubin-10-sulfonate (ranarubin), a naturally occurring bile pigment, including determination of its mixed acidity constants (pKa*). Thanks to the presence of the sulfonic acid moiety, this compound is more polar compared to UCB, which might theoretically solve the problem with an accurate determination of the UCB pKa* values of its propionic acid carboxylic groups. Bilirubin-10-sulfonate was synthesized by modification of a previously described procedure; and its properties were studied by mass spectrometry (MS), nuclear magnetic resonance (NMR), infrared (IR), and circular dichroism (CD) spectroscopy. Determination of pKa* values of bilirubin-10-sulfonate and UCB was performed by capillary electrophoresis with low pigment concentrations in polar buffers. The identity of the synthesized bilirubin-10-sulfonate was confirmed by MS, and the pigment was further characterized by NMR, IR, and CD spectroscopy. The pKa values of carboxylic acid moieties of bilirubin-10-sulfonate were determined to be 5.02, whereas those of UCB were determined to be 9.01. The physico-chemical properties of bilirubin-10-sulfonate were partially characterized with low pKa* values compared to those of UCB, indicating that bilirubin-10-sulfonate cannot be used as a surrogate pigment for UCB chemical studies. In addition, using a different methodological approach, the pKa* values of UCB were found to be in a mildly alkaline region, confirming the conclusions of a recent critical re-evaluation of this specific issue.

Enantioselective interaction of carbamoylated quinine and (S)-3,5-dinitrobenzoyl alanine: theoretical and experimental circular dichroism study.

The interaction between tert-butylcarbamoylquinine selector and (S)-3,5-dinitrobenzoyl alanine selectand was studied experimentally and theoretically by chiroptical methods. Using a combination of experimental and calculated circular dichroism spectra, we present the first work dealing with the interaction of two dissimilar chiral molecules interacting by diverse types of interactions: ion pairing, hydrogen bonding and π-π stacking. Conformational analysis of the free selector, free selectand and the complex of selector with selectand was carried out and the obtained conformers were optimized at the BHandH/6-31+G** and B97d/6-31+G** levels. Consequently, vibrational (VCD) and electronic (ECD) circular dichroism spectra were calculated at the BHandH/6-31+G** and B97d/6-31+G** levels for the VCD and HF/6-31++G** and CAM-B3LYP/6-31++G** levels for the ECD. Spectral patterns of the free selectand and selector together with the complexation-induced spectral changes were compared with experimental data. Despite many simplifications within the theoretical model, the calculated ECD and VCD spectra are in good agreement with experimental data, which proves that the density functional theory (DFT) methods are able to model complicated systems interacting via multiple interactions of different natures.