Chiroptical properties of S-proline conformational isomers

The chiroptical properties of S-proline conformational isomers are examined on a theoretical model in which electronic wave functions are obtained from semiempirical molecular orbital calculations. The CNDO/S molecular orbital model is used to perform SCF-MO calculations on ground state electronic structure and excited states are constructed in the virtual orbital-configuration interaction approximation. Electronic rotatory strengths and dipole strengths are calculated directly from the complete (but approximate) molecular electronic wave functions. Zwitterionic, cationic, and anionic S-proline structures are studied twotypes of conformational variables are represented in the calculations: (1) pyrrolidine ring conformation; and (2) rotation about the C^α-COO^? bond. Rotatory strengths are found to be somewhat sensitive to rotational isomerism about the C^α-COO^? bond, but are found to be rather insensitive to conformational changes within the pyrrolidine ring. The CD spectrum of zwitterionic S-proline down to ～160 nm appears to be well accounted for by the theoretically calculated results if conformational preferences with respect to rotation about the C^α-COO^? bond can be assumed to exist in solution media. Furthermore, spectra-structure correlations are offered for the anionic and cationic forms of S-proline in solution.     

Optical rotatory properties of L-cystine conformational isomers. Theoretical analysis

The near ultraviolet chiroptical properties of L -cystine conformational isomers are examined on a static, “one-electron” model in which the disulfide moiety is the chromophoric group and the atoms of the L -alanyl fragments are treated as perturbers. The zeroth order chromophoric wave functions are calculated on a semiempirical molecular orbital model in which excited states are constructed in the virtual orbital-configuration interaction approximation. The perturbing environment is represented by point charges located at the atomic centers of the L -alanyl fragments. Chromophore–perturber interactions are expressed as charge–multipole moments with only the charge–dipole and charged–quadrupole terms being retained in the calculations. Vicinal contributions to the rotatory strengths of the five lowest energy disulfide transitions are computed for 30 conformational isomers of the L -cystine dizwitterion. The results provide support for the view that vicinal or peripheral effects can account entirely for the observed near ultraviolet (λ > 230 nm) chiroptical properties of L -cystine and its derivatives and that these properties are diagnostic of conformational features external to the disulfide moiety.     

The optical properties of alanine and proline diketopiperazines

The optical properties of the diketopiperazine chromophore of the cyclic dipeptides have been investigated as a function of molecular conformation. The rotatory strengths of L -alanyl–L -alanine diketopiperazine and L -prolyl–L -proline diketopiperazine have been calculated as a function of the angle of fold of the diketopiperazine ring. The results of these theoretical calculations have been compared with experimental circular dichroism and optical rotatory dispersion data. It is shown that the observed optical properties of these molecules can be explained only if their diketopiperazine rings are folded in opposite directions. The direction of fold is established for each molecule. In solution, the diketopiperazine ring of L -alanyl-L -alanine diketopiperazine is folded in the direction opposite to that found by X-ray diffraction analysis of crystals. It has been observed that the degree of conservatism of the π → π* couplet of L -propyl–L -proline diketopiperazine depends markedly upon the nature of the solvent that is used. In addition, a shoulder has been discovered in the CD spectrum of L -alanyl–L -alanine diketopiperazine, which may not be directly attributable to the n → π* and π → π* transitions of the peptide chromophores.     

Ab initio (CASPT2) excited state calculations, including circular dichroism, of helically twisted cyanine dyes

Ab initio calculations at the CASSCF/CASPT2 level were performed on helically twisted mono-, tri-, and pentamethine cyanine dyes in the all-Z-configurations. Excitation energies and oscillator and rotatory strengths were calculated for the five lowest energy singlet states. Both the long wavelength methine band and the cis-band could be identified unambiguously from their configurational parentage. The calculated state energies are within 0.09 eV of the experimental value for the methine band and within 0.16 eV for the cis-band. The calculated rotatory strengths of the methine band shows sign inversion as the length of the chromophore increases: negative for the short monomethine, strongly positive for the pentamethine. The trimethine presents a borderline case: the measured rotatory strength is almost nil, the calculated one depends on the geometry. There is good agreement between rotatory strengths calculated in the velocity and in the length formalism.     

The chiroptical properties of proteins. II. Near-ultraviolet circular dichroism of lysozyme

A study of the near-uv CD spectrum of lysozyme was carried out in the presence and absence of the inhibitor tri-N-acetylglucosamine, and theoretical chiroptical calculations based on the tetragonal crystal structure of the enzyme and the enzyme-inhibitor complex were performed. The results of these calculations indicate that the near-uv CD spectrum of lysozyme can be adequately explained in terms of negative rotatory strengths arising from the tryptophan ¹L_a (293–300 nm) and the disulfide n-σ* bands (250 rm), and positive rotatory strength contributions from the tryptophan ¹L_b bands (291 nm) and the tyrosine ¹L_b bands (275 nm). Contributions to the rotatory strength of each band were approximated in terms of specific interactions between chromophores. It was found that the rotatory strength of most of the near-uv transitions arises primarily from coupling interactions involving other side-chain chromophores and amide groups which are in close proximity. Changes which are observed in the lysozyme CD spectrum on binding of tri-N-acetylglucosamine may be explained in terms of changes in the rotatory strength which result from interactions of the ¹L_a transitions of the active-site tryptophans with the acetamide groups of the inhibitor. The reasonable agreement which is found between the experimental and calculated rotatory strengths implies that the crystal conformation of lysozyme must resemble the solution conformation.     

Origin and consequences of steric strain in the rhodopsin binding pocket

To study the origin and the effects of steric strain on the chromophore conformation in rhodopsin, we have performed quantum-mechanical calculations on the wild-type retinal chromophore and four retinal derivatives, 13-demethyl-, 10-methyl-13-demethyl-, 10-methyl-, and 9-demethylretinal. For the dynamics of the whole protein, a combined quantum mechanics/molecular mechanics method (DFTB/CHARMM) was used and for the calculation of excited-state properties the nonempirical CASSCF/CASPT2 method. After relaxation inside the protein, all chromophores show significant nonplanar distortions from C10 to C13, most strongly for 10-methylretinal and least pronounced for 9-demethylretinal. In all five cases, the dihedral angle of the C10-C11=C12-C13 bond is negative which attests to the strong chiral discrimination exerted by the protein pocket. The calculations show that the nonplanar distortion of the chromophore, including the sense of rotation, is caused by a combination of two effects: the fitting of both ends to the protein matrix which imposes a distance constraint and the bonding arrangement at the Schiff base terminus. With both the counterion Glu113 and Lys296 displaced off the plane of the chromophore, their binding to N16 exerts a torque on the chromophore. As a result, the polyene chain, from N16 to C13, is twisted in a clockwise manner against the remaining part of the chromophore, leading to a C11=C12 bond with the observed negative dihedral angle. Shifts of the absorption maxima are reproduced correctly, in particular, the red shift of the 10-methyl and the strong blue shift of the 9-demethyl analogue relative to the wild type. Calculated positive rotatory strengths of the alpha-CD bands are in agreement with the calculated absolute conformation of the mutant chromophores.     

Density functional theory calculations of optical rotation: employment of ADZP and its comparison with other basis sets

Density function theory calculations of frequency dependent optical rotations ([alpha]omega) for 30 rigid chiral molecules are reported. Calculations have been carried out at the sodium D line frequency, using the augmented double zeta valence quality plus polarization functions (ADZP) basis set and the BP86 nonhybrid and B3LYP hybrid functionals. Gauge-invariant atomic orbitals were used to guarantee origin-independent values of [alpha]D. Comparison between corresponding results obtained with nonhybrid and hybrid functionals as well as with theoretical optical rotations reported in the literature is done. Excited electronic states of three molecules are also discussed in light of circular dichroism spectra and B3LYP and BP86 calculated excitation energies and rotatory strengths. One verifies that the B3LYP/ADZP results are in better agreement with experiment.     

Cyclic oxyphosphoranes as model intermediates during splicing and cleavage of RNA: ab initio molecular orbital calculations on the conformational analysis.

Ab initio molecular orbital calculations have been carried out on hydrated adducts of methyl ethylene phosphate as a model intermediate during cleavage of RNA. Upon rotating the apical methoxyl group two kinds of stable conformers and two kinds of rotational transition states are located, the most stable conformation being gs-G where the dihedral angle between the apical methyl group and the basal ring oxygen is calculated to be 76 degrees. In this gs-G conformation one of the lone pairs on the apical oxygen is oriented antiperiplanar to the basal ring ester bond. The torsional energy required to rotate the methyl group about the phosphorus-apical oxygen bond leading to ts-C conformation, where the methyl group is eclipsed with the ring oxygen, is calculated to be 5.2 kcal/mol. Judging from the published substrate's coordinates in the RNase environment, the expected pentacoordinate-intermediate/transition state during the cleavage of RNA appears to be, in fact, the most stable gs-G conformation.     

Consistent force field calculations on 2,5-diketopiperazine and its 3.6-dimethyl derivatives

The minimum energy conformations are calculated for 2, 5-diketopiperazine (DKP) and its 3,6-dimethyl derivatives (DL-DMDKP and LL-DMDKP), using a consistent force field approach developed previously. The energy function parameters that were not required in earlier calculations on alkanes, amides, mid lactams are fitted to spectral and conformational data on the diketopiperazines. Vibrational assignments are suggested for DKP. Conformational energies are also determined over a range of selected values for ring dihedral angles, and the shape of the potential energy functions is examined over deviations from planarity. DKP and LL-DMDKP are found to have non-planar minimum energy conformations, separated from planar by less than a kcal/mole. DL-DMKP exhibits a nearly flat trough about the planar conformation. Calculations of minimum energies with one dihedral angle coordinate constrainted show a coupling between bond angles and dihedral angles in agreement with recent suggestions of Benedetti.     

Isolation and structural determination of the antifouling diketopiperazines from marine-derived Streptomyces praecox 291-11

Marine derived actinomycetes constituting 185 strains were screened for their antifouling activity against the marine seaweed, Ulva pertusa, and fouling diatom, Navicula annexa. Strain 291-11 isolated from the seaweed, Undaria pinnatifida, rhizosphere showed the highest antifouling activity and was identified as Streptomyces praecox based on a 16S rDNA sequence analysis. Strain 291-11 was therefore named S. praecox 291-11. The antifouling compounds from S. praecox 291-11 were isolated, and their structures were analyzed. The chemical constituents representing the antifouling activity were identified as (6S,3S)-6-benzyl-3-methyl-2,5-diketopiperazine (bmDKP) and (6S,3S)-6-isobutyl-3-methyl-2,5-diketopiperazine (imDKP) by interpreting the nuclear magnetic resonance and high-resolution mass spectroscopy data. Approximately 4.8 mg of bmDKP and 3.1 mg of imDKP were isolated from 1.2 g of the S. praecox 291-11 crude extract. Eight different compositions of culture media were investigated for culture, the TBFeC medium being best for bmDKP and TCGC being the optimum for imDKP production. Two compounds respectively showed a 17.7 and 21 therapeutic ratio (LC50/EC50) to inhibit zoospores, and two compounds respectively showed a 263 and 120.2 therapeutic ratio to inhibit diatoms.     

Electronic and vibrational circular dichroism of aromatic amino acids by density functional theory

Structures of model compounds mimicking aromatic amino acid residues in proteins are optimized by density functional theory (DFT), assuming that the main-chain conformation was a random coil. Excitation energies and dipole and rotational strengths for the optimized structures were calculated based on time-dependent DFT (TD-DFT). The electronic circular dichroism (ECD) bands of the models were significantly affected by side-chain conformations. Hydration models of the aromatic residues were also subjected to TD-DFT calculations, and the ECD bands of these models were found to be highly perturbed by the hydration of the main-chain amide groups. In addition to calculating the random-coil conformation, we also performed TD-DFT calculations of the aromatic residue models, assuming that the main-chain conformation was an alpha-helix or beta-strand. As expected, the overall feature of the ECD bands was also perturbed by the main-chain conformations. Moreover, vibrational circular dichroism (VCD) spectra of the hydration models in a random-coil structure were simulated by DFT, which showed that the VCD spectra are more sensitive to the side-chain conformations than the ECD spectra. The present results show that analyses combining ECD and VCD spectroscopy and using DFT calculations can elucidate the main- and side-chain conformations of aromatic residues in proteins.     

Exciton interactions in dimers of bacteriochlorophyll and related molecules

Formalisms are developed for calculating the absorption wavelengths, dipole strengths and rotational strengths for dimers of bacteriochlorophyll and related molecules. The expressions explicitly consider the mixing of bacteriochlorophyll's four main excited states (Q_y, Q_x, B_x and B_y) in the ground and excited states of the dimer. This mixing must be considered in order to account for the hyperchromism and nonconservative circular dichroism found experimentally in oligomers of bacteriochlorophyll and bacteriopheophytin. The spectroscopic properties of the eight absorption bands of a bacteriopheophytin dimer are calculated as functions of the geometry of the dimer. The importance of the mixing of nondegenerate excited states, and of the mixing of doubly-excited states into the dimer's ground state, is evaluated by comparisons with calculations in which these phenomena are neglected. Structures for bacteriopheophytin dimers are found for which most of the calculated spectroscopic properties are consistent with the properties seen experimentally. Possible explanations are considered for the remaining discrepancies between the calculated and observed properties.     

Contribution of side-chain chromophores to the optical activity of proteins: model compound studies. I. Alpha-methyl-L-tyrosine

The optical rotatory power and the conformational energy of the amino acid α-methyl-L -tyrosine has been calculated as a function of molecular conformation. Comparison of the results of these theoretical calculations with experimental circular dichroism data indicates that the conformational freedom of this molecule is highly restricted. The most heavily populated conformations appear to be those near χ1 = 60°, χ2 = 80°, Ψ = 175°, and χ1 = 300°, χ2 = 80°, Ψ = 5°. The χ1 = 180° conformations are not likely to be populated to a significant extent at ordinary temperatures.     

Molecular modeling of poly(ethylene oxide) model cofactors; 1,3,6-tri-O-galloyl-β-<Emphasis Type="SmallCaps">d</Emphasis>-glucose and corilagin

The most stable structures of two poly(ethylene oxide) (PEO) model cofactors, beta-1-O-galloyl-3,6-( R)-hexahydroxydiphenoyl- d-glucose (corilagin) and 1,3,6-tri-O-galloyl-beta- d-glucose (TGG), are calculated using molecular modeling and PM3 semiempirical molecular orbital theories. The theoretical PM3 structures agree with interpreted structures from experimental NMR; the glucopyranose ring of corilagin has a boat and TGG a chair conformation, for which the heats of formation, torsion angles, distances, van der Waals surface, and the infrared spectra are calculated.     

Chemical evidence of preserved collagen in 54-million-year-old fish vertebrae

Collagens are the most abundant proteins in the animal kingdom. They form the structural framework of connective tissues such as bones, tendons and skin, and play important biomechanical role in supporting tissue functions. The preservation of collagen in deep time is a topic of intense debate. Here we provide indisputable evidence for the presence of collagen in early Eocene fish vertebrae using online pyrolysis comprehensive two dimensional gas chromatography time-of-flight mass spectrometry (py-GC×GC-TOFMS) and immunofluorescence analysis. The presence of cyclic dipeptides such as diketodipyrrole, 2,5-diketopiperazine of proline-proline and 2,5-diketopiperazine of proline-glycine along with other nitrogen-bearing molecules in the pyrolysis products of the studied fossils unequivocally demonstrate that collagen can withstand degradation and diagenetic alteration. Immunofluorescence study also confirms the presence of collagen-I in the fossilized fish vertebrae. Contrary to common opinion, the present findings suggest that the preservation of collagen in fossilized soft tissues is not rare. We propose that one of the essential factors controlling preservation of collagen is the establishment of a suitable microenvironment within the fossil, inhibiting diagenetic alteration including microbial decay.     

Optical and conformational properties of the 7-(beta-D-ribofuranosyl) purines

The optical and conformational properties of certain 7-ribosyl purines have been studied using several experimental and theoretical methods. The CD, MCD, and absorption spectra of the 7-ribosyl purines and their cations have been determined experimentally with some solvent effects being noted. Theoretically we have used the SCF-CI and CNDO molecular orbital calculations to determine the optical properties of the bases; Simpson's bond exciton theory to determine the optical properties of the bases; Simpson's bond exciton theory to determine the optical properties of the ribose moiety; the optical activity was determined by the dipole coupling and electricmagnetic coupling equations; and the conformational energy calculations are included as a basis for excluding highly improbable conformations. On the basis of these calculations, we concluded that the oxy derivatives and the amino derivatives are predominately in the “extreme anti” conformation and “standard anti” conformation, respectively. However, the conclusions are tentative since at the present time the band assignments are not unequivocal. At least one n-π* transition has been identified in the spectra which is not notably sensitive to pH and solvent effects. Several implications of this observation are discussed.     

Ab initio self-consistent field and potential-dependent partial equalization of orbital electronegativity calculations of hydration properties of N-acetyl-N'-methyl-alanineamide

Using a recently developed parallel computation algorithm, ab initio self-consistent field (SCF) calculations were carried out to estimate the relative hydration energies for 12 low-energy conformations of N-acetyl-N'-methyl-alanineamide. The requisite SCF calculations were carried out using 6-31G and 6-31G* basis sets, both in the absence and presence of a perturbing potential arising from a model solvent. The alpha R, alpha L, polyproline II (PII), and pi helical conformations were preferentially stabilized by the solvent potential, whereas conformations with intramolecular hydrogen-bonding C5 and C7 were preferred in the gas phase. Average vicinal nmr coupling constants (JNH-C alpha H), calculated using the total energies of the various solvated conformations, were consistent with observed coupling constants for this peptide in aqueous solution. Substantial alteration of the solute charge density occurred upon equilibration with the reaction field, as was exemplified in changes both in the molecular dipole moments and in atom-centered multipoles, when the molecule was transferred from a medium of low dielectric constant to one of high dielectric constant. In order to model these changes in charge density with an empirical scheme, we have implemented a novel monopolar representation of the solute charge density based on a potential-dependent form of partial equalization of orbital electronegativities (PDPEOE). In the atom-centered point charge PDPEOE representation, charge flows from one region of the solute to another in response to external fields. Hydration energies calculated using the PDPEOE representation are similar to those calculated by the SCF procedure. Also, the PDPEOE calculations yielded changes in molecular dipole moments upon solvation that agreed closely with the changes in the calculated ab initio SCF dipole moments.     

Contribution of side-chain chromophores to the optical activity of proteins: Model compound studies. IV. The indole chromophore of yohimbinic acid.

The optical properties of the indole chromophore of the indole alkaloid yohimbinic acid have been investigated as a function of molecular conformation. Theoretical rotatory strengths have been calculated and compared with experimental circular dichroism spectra. Optical data that may be suitable for calculating the chiroptical properties of the near ultraviolet electronic transitions of the indole chromophores, which occur in tryptophan residues of proteins, have been developed. The far ultraviolet transitions of yohimbinic acid have also been investigated.     

Calculated optical properties of 64 trinucleoside diphosphates

The optical rotatory dispersion and ultraviolet absorption spectra of the 64 trinucleoside diphosphates containing the bases A, U, C, and G have been calculated by using a simple semiempirical approach. These calculations accurately predict the optical properties of the nine trimers for which extensive experimental results are available. The computed optical data should be useful in the identification of oligonucleotides obtained in the course of sequence determination of ribonucleic acids and should simplify the determination of the concentration of oligonucleotides in aqueous solution. Additional calculations indicate that it should be possible to analyze most, mixtures of sequence isomers of trinucleoside diphosphates by direct, measurement of the ORD of the mixture at neutral pH.     

Quantitative analysis of absorption spectra and spectra of magneto-optical rotatory dispersion of hemoproteins with reference to zero-field splitting. I. Analysis of the divalentcation of deuteroporphyrin in the Q-band region]

I. Analysis of the dication of deuteroporphyrin in the Q-band region. Methods for quantitative analysis of absorption spectra and magneto-optical rotatory dispersion with regard to zero-field splitting of a nearly degenerated term for the latter are described. The methods are based on adaptation of band-form functions to the spectrum using the principle of least squares. Calculation of the zero-field splitting utilizes the formalism evolved by Stephens for strictly degenerated terms (A-terms in the magneto-optical spectrum) which has been further developed to a band-form function depending on zero-field splitting. The curve-form function of the modified A-term contains 4 parameters (zero-field splitting, rotational strength, band width, and the maximum of the band) which have been determined by a computer program. The oscillator and the dipole strength of absorption bands to be calculated simultaneously with the program allows the determination of the magnetic orbital moments of the terms. Exemplified by the dication of deuteroporphyrindimethylester, the significance of zero-field splitting for the recognition of the exact molecule symmetry is demonstrated, and a model of the molecular structure is proposed.