Exciton-coupled CD Research Articles

The role of magnetic-electric coupling in exciton-coupled ECD spectra: the case of bis-phenanthrenes.

Apparent exceptions to the exciton chirality method may arise for chromophores undergoing transitions which are both electric- and magnetic-dipole allowed, for example bis-phenanthrenes. We present a computational approach to calculate exciton-coupled CD spectra based on a quantum-mechanical description of the excitonic parameters, which also includes the solvent effects.

Breakdown of Exciton Splitting through Electron Donor–Acceptor Interaction: A Caveat for the Application of Exciton Chirality Method in Macromolecules

Circular dichroism spectra for a series of structurally analogous hairpin oligonucleotides, tethered at the 5′-end with an axially chiral naphthalenimide-perylenimide dyad (NP), is dependent on the nature (AT vs GC) and the orientation (5′-C vs 5′-G) of the adjacent base pair that stacks with the dyad. Charge transfer (CT) interaction between the naphthalenimide unit of the dyad NP and the adjacent guanine–cytosine (5′-C) base pair has been characterized by UV–vis absorption and fluorescence measurements. Molecular dynamics simulations of the dyad end-capped hairpin DNA ODN6i and TD-DFT calculations of the naphthalenimide and perylenimide units confirm that the CT transition dipole orients perpendicular to the perylenimide transition dipole. The orthogonality of the cross product of the CT and the perylenimide transition dipoles with the displacement vector connecting the two dipoles in space results in the zeroing out of the rotational strength of the perylenimide transition dipole, subsequently leading to the DNA-induced nonexciton coupled circular dichroism corresponding to perylenimide, in concurrence with experimental CD spectrum. Singular value decomposition of thermal denaturation of the hairpin DNA having CT interaction (ODN6i) revealed the denaturation proceeded through an additional intermediary stage compared to the hairpin DNA without the CT interaction (ODN6). Dissimilar CD (induced CD for ODN6i vs exciton-coupled CD for ODN6) spectra corresponding to perylenimide unit obtained for similar NP end-capped hairpin DNA sequences cautions against the indiscriminate use of the exciton chirality method, particularly in systems like DNA and proteins containing polarizable chromophores that can interact with reporter transition dipoles.

Role of Environmental Factors on the Structure and Spectroscopic Response of 5′‐DNA–Porphyrin Conjugates Caused by Changes in the Porphyrin–Porphyrin Interactions

We have explored the utility, strength, and limitation of through-space exciton-coupled circular dichroism in determination of the secondary structure of optically active chromophoric nanoarrays using the example of end-capped porphyrin- and metalloporphyrin-oligodeoxynucleotide conjugates. We put special emphasis on the explanation of the origin and significance of the distinctive multiple bands in the CD spectra (trisignate and tetrasignate CD bands). Such CD profiles are often observed in chiral aggregates or multichromophoric arrays but have never before been studied in detail. We found that variation of temperature and ionic strength has a profound effect on the geometry of the porphyrin-DNA conjugates and thus the nature of electronic interactions. At lower temperatures and in the absence of NaCl all three 5'-DNA-porphyrin conjugates display negative bisignate CD exciton couplets of variable intensity in the Soret region resulting from through-space interaction between the electric transition dipole moments of the two end-capped porphyrins. As the temperature is raised these exciton couplets are transformed into single positive bands originating from the porphyrin-single-strand DNA interactions. At higher ionic strengths and low temperatures, multisignate CD bands are observed in the porphyrin Soret region. These CD signature bands originate from a combination of intermolecular, end-to-end porphyrin-porphyrin stacking between duplexes and porphyrin-DNA interactions. The intermolecular aggregation was confirmed by fluorescence and absorption spectroscopy and resonance light scattering. DeVoe theoretical CD calculations, in conjunction with molecular dynamics simulations and Monte Carlo conformational searches, were used to mimic the observed bisignate exciton-coupled CD spectra as well as multiple CD bands. Calculations correctly predicted the sign and shape of the experimentally observed CD spectra. These studies reveal that the exciton-coupled circular dichroism is a very useful technique for the determination of the structure of optically active arrays.

Thiourea and isothiocyanate – two useful chromophores for stereochemical studies. A comparison of experiment and computation

Thioureas and isothiocyanates, compounds of high importance in organic synthesis, have not been considered so far as chiroptical probes that can provide structural information from the analysis of circular dichroism spectra. CD spectra of a set of molecules containing the thiourea, isothiocyanate and phthalimide chromophores were obtained and analyzed on the grounds of the calculated populations of conformers and their individual contributions to the CD spectra. It is shown that the thiourea and isothiocyanate chromophores can provide useful structural information from the analysis of their exciton-coupled CD spectra. Exciton-coupled CD spectra of thioureas were found to be sensitive to the Z/E conformation of the chromophore. DFT calculations based on the B2LYP functional were shown to provide a better match with the experimental spectra collected in the short wavelength region, compared to the traditionally used B3LYP functional.

Quantum Chemical Investigation of Exciton Coupling: Super‐Molecular Calculations of a Merocyanine Dimer Aggregate

(Figure Presented) Theoretical spectroscopy: The first wave-function based super-molecular computation of an exciton-coupled electronic CD spectrum for a merocyanine dimer is presented. Results are based on a fully DFT-D optimized structure and excitation energies are obtained with the perturbative SCS-CIS(D) approach. The theoretical data are in very good agreement with those from experiment. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

Circular dichroism of tocopherols versus tocotrienols

Vitamin E is an essential nutrient of still increasing economic importance. Vitamin E derivatives include many nonracemic chiral compounds whose chirooptical characterization is scarcely described in the literature. We report the CD spectra of delta-tocopherol and its unsaturated analog delta-tocotrienol. TDDFT calculations demonstrate that the weak CD of delta-tocopherol is determined by the helicity of dihydropyrane ring. In addition, the moderate CD of delta-tocotrienol is due to the exciton interaction between the aromatic ring and the closest alkene group. Direct exciton-coupled CD calculations on structures generated by two different conformational sampling approaches reveal that, although such exciton coupling is expected to be weak, it is sufficient to explain the spectral differences between tocopherol and tocotrienol.

Fluorinated Porphyrin Tweezer: A Powerful Reporter of Absolute Configuration forerythroandthreoDiols, Amino Alcohols, and Diamines

A general and sensitive nonempirical protocol to determine the absolute configurations of erythro and threo diols, amino alcohols, and diamines is reported. Binding of diols to the porphyrin tweezer system is greatly enhanced by increasing the Lewis acidity of the metalloporphyrin. Supramolecular complexes formed between the porphyrin tweezer host and chiral substrates exhibited exciton-coupled bisignate CD spectra with predictable signs based on the substituents on the chiral center. The working model suggests that the observed helicity of the porphyrin tweezer is dictated via steric differentiation experienced by the porphyrin ring bound to each chiral center. A variety of erythro and threo substrates were investigated to verify this chiroptical method. Their absolute configurations were unequivocally determined, and thus a general mnemonic is provided for the assignment of chirality.

Interaction of rac-[Cu(diimine)3]2+ and rac-[Zn(diimine)3]2+ complexes with CT DNA: effect of fluxional Cu(ii) geometry on DNA binding, ligand–promoted exciton coupling and prominent DNA cleavage

The complexes [Cu(phen)(3)](ClO(4))(2) 1, [Cu(5,6-dmp)(3)](ClO(4))(2) 2, [Cu(dpq)(3)](ClO(4))(2) 3, [Zn(phen)(3)](ClO(4))(2) 4, [Zn(5,6-dmp)(3)](ClO(4))(2) 5 and [Zn(dpq)(3)](ClO(4))(2) 6, where phen = 1,10-phenanthroline, 5,6-dmp = 5,6-dimethyl-1,10-phenanthroline and dpq = dipyrido[3,2-d:2',3'-f]quinoxaline, have been isolated, characterized and their interaction with calf thymus DNA studied by using a host of physical methods. The X-ray crystal structures of rac-[Cu(5,6-dmp)(3)](ClO(4))(2) and rac-[Zn(5,6-dmp)(3)](ClO(4))(2) have been determined. While 2 possesses a regular elongated octahedral coordination geometry (REO), 5 possesses a distorted octahedral geometry. Absorption spectral titrations of the Cu(II) complexes with CT DNA reveal that the red-shift (12 nm) and DNA binding affinity of 3 (K(b), 7.5 x 10(4) M(-1)) are higher than those of 1 (red-shift, 6 nm; K(b), 9.6 x 10(3) M(-1)) indicating that the partial insertion of the extended phen ring of dpq ligand in between the DNA base pairs is deeper than that of phen ring. Also, 2 with a fluxional Cu(II) geometry interacts with DNA (K(b), 3.8 x 10(4) M(-1)) more strongly than 1 suggesting that the hydrophobic forces of interaction of 5,6 methyl groups on the phen ring is more pronounced than the partial intercalation of phen ring in the latter with a static geometry. The DNA binding affinity of 1 is lower than that of its Zn(ii) analogue 4, and, interestingly, the DNA binding affinity 2 of with a fluxional geometry is higher than that of its Zn(II) analogue 5 with a spherical geometry. It is remarkable that upon binding to DNA 3 shows an increase in viscosity higher than that the intercalator EthBr does, which is consistent with the above DNA binding affinities. The CD spectra show only one induced CD band on the characteristic positive band of CT DNA upon interaction with the phen (1,4) and dpq (3,6) complexes. In contrast, the 5,6-dmp complexes 2 and 5 bound to CT DNA show exciton-coupled biphasic CD signals with 2 showing CD signals more intense than 5. The Delta-enantiomer of rac-[Cu(5,6-dmp)(3)](2+) 2 binds specifically to the right-handed B-form of CT DNA at lower ionic strength (0.05 M NaCl) while the Lambda-enantiomer binds specifically to the left-handed Z-form of CT DNA generated by treating the B-form with 5 M NaCl. The complex 2 is stabilized in the higher oxidation state of Cu(II) more than its phen analogue 1 upon binding to DNA suggesting the involvement of electrostatic forces in DNA interaction of the former. In contrast, 3 bound to DNA is stabilized as Cu(I) rather than the Cu(II) oxidation state due to partial intercalative interaction of the dpq ligand. The efficiencies of the complexes to oxidatively cleave pUC19 DNA vary in the order, 3> 1 >> 2 with 3 effecting 100% cleavage even at 10 microM complex concentration. However, interestingly, this order is reversed when the DNA cleavage is performed using H(2)O(2) as an activator and the highest cleavage efficiency of 2 is ascribed to its electrostatic interaction with the exterior phosphates of DNA.

Regulation of electronic behavior via confinement of PPV-based oligomers on peptide scaffolds

Intermolecular interactions dramatically affect the structure/property relationships of electroactive molecules in device environments and have been the subject of significant research effort. Purposeful manipulation of the distance between chromophores is a key parameter in such investigations, although such manipulation has proven difficult. Systems in which distances between chromophores can be controlled serve both as model systems for understanding structure/property relationships in more depth, as well as potential active components in devices. In this work, oxadiazole-containing poly(phenylenevinylene) (Oxa-PPV) oligomers have been chemically attached in specific positions to an α-helical peptide scaffold, which permits the presentation of the Oxa-PPV side-chains at distances of nominally 6 Å and 11 Å apart on the same side and also 7 Å apart on opposite sides of the peptide. The Oxa-PPV side-chains were attached to the peptide scaffolds via straightforward Heck coupling strategies; the resulting modified peptides were characterized by a variety of spectroscopic methods. Circular dichroic spectroscopy (CD) confirmed the helical conformation of the scaffolds modified with the bulky conjugated side-chains, and suggested that side-chain interactions may improve the thermal stability of the molecules. Exciton-coupled CD measurements confirmed the interactions of the conjugated side-chains and detected subtle apparent differences in side-chain orientation that were also indicated in computational modeling of the molecules. Photoluminescence spectroscopy confirmed the electronic interaction of the side-chains; the results clearly captured differences in luminescence as a function of chromophore presentation, and further indicated differences in excited state species with differences in chromophore presentation. The observed effects indicate not only that bulky chromophores can be presented on helical peptide templates without loss of template conformation, but also that such presentation may accurately capture details of electronic transport between molecules commonly employed in organic electronic applications.

Amaranzole A, a New N-Imidazolyl Steroid from Phorbas amaranthus

An unprecedented 24-N-imidazolyl steroidal alkaloid, amaranzole A, was isolated from a tropical sponge, Phorbas amaranthus. The structure was solved by interpretation of MS, NMR, including a novel exciton-coupled CD spectrum due to an allyl imidazole, and comparison with model compounds.

Synthesis and Aggregation Behavior ofmeso-Sulfinylporphyrins: Evaluation of S-Chirality Effects on the Self-Organization to S–Oxo-Tethered Cofacial Porphyrin Dimers

The synthesis and aggregation behavior of meso-sulfinylporphyrins are described. The copper-catalyzed C-S cross-coupling reaction of a meso-iodoporphyrin with benzenethiol and n-octanethiol has proved to be an efficient method for the synthesis of meso-sulfanylporphyrins, which are oxygenated by m-chloroperbenzoic acid to produce the corresponding meso-sulfinylporphyrins. Optically active zinc meso-sulfinylporphyrins were successfully isolated by means of optical resolution of the racemates on a chiral HPLC column. Zinc sulfinylporphyrins readily undergo self-organization through S-oxo-zinc coordination to form cofacial porphyrin dimers in solution, in which the hetero- and homodimers are present as a diastereomeric mixture. The aggregation modes of the S-oxo-tethered porphyrin dimers were fully characterized by 1H NMR, IR, and UV/Vis spectroscopy as well as DFT calculations on their model compounds, thus revealing that the self-aggregation behavior depends on the combination of S chirality. The absolute configurations at the sulfur center can be determined by the exciton-coupled CD method. The observed self-association constant for the S-oxo-tethered dimerization of (S)-phenylsulfinylporphyrin in toluene is larger than that in dichloromethane, which reflects the difference in dipole moments between the homodimer and the monomer. In cyclic and differential pulse voltammetry, the first oxidation process of the cofacial dimers is split into two reversible steps, which indicates that the initially produced pi radical cations are delocalized efficiently between the two porphyrin rings. The present findings demonstrate the potential utility of meso-sulfinyl groups as promising ligands for investigating the effects of peripheral chirality on the structures and optical and electrochemical properties of metal-assisted porphyrin self-assemblies.

L-Lysine-linked anthracenophane derived from thermodynamically controlled intermediates

We easily and simply synthesized l-lysine-linked anthracenophane from [2+2] macrocyclization between anthracene-9,10-dicarboxaldehyde and l-lysine methyl ester by thermodynamically controlled process. The structure was characterized by single crystal X-ray resolution and 1H NMR. Circular dichroism spectrum showed induced-CDs including exciton-coupled CD, suggesting that intramolecular anthracene moieties exist in chiral arrangement. The resultant anthracenophane can form a 1:1 complex with a silver(I) ion in its cavity via NH-metal coordination and cation–π interaction ( K a = 2.62 × 10 5 M −1).

Long-Range Exciton-Coupled Circular Dichroism: Application for Determination of the Absolute Configuration of Oligonaphthalenes

Hexadecanaphthalenes (S,S,S,S,S,S,S,S,S,S,S,S,S,S,S)-4b and (S,S,S,S,S,S,S,R,S,S,S,S,S,S,S)-4b that possess two tetraphenylporphyrins (TPP) on the upper and lower naphthalene rings were synthesized. Long-range exciton-coupled CD in the Soret region of TPP (about 66 A) was observed. [structure: see text]

Fluorescence Detected Circular Dichroism for Highly Sensitive Observation of Exciton Coupled CD

The fluorescence detected circular dichroism (FDCD) appearance of some exciton coupling compounds is reviewed by a newly developed ellipsoidal mirror system (FDCD465). The FDCD465 achieves both the complete elimination of the polarization artifact and a dramatic enhancement of detection sensitivity expanding the applicability of exciton coupling fluorophores. A variety of chromophores that possess large extinction coefficients and high fluorescence quantum yields are available for exciton coupled FDCD, regardless of the degree of fluorescence polarization. Different types of FDCD devices can regulate FDCD polarization artifacts and the photoselection effect, enabling effective surveys of FDCD potential.

Chiral recognition of cyclic α‐hydroxyketones by CD‐sensitive zinc tetraphenylporphyrin tweezer

A combined chemical/chiroptical microscale protocol for the determination of absolute configurations of cyclic alpha-hydroxyketones is described. The hydroxyl group in cyclic alpha-hydroxyketones is converted into (3-aminopropylamino)acetate (NH2CH2CH2CH2NHCH2COOR), or more generally, according to a newly developed protocol, into (3-hydroxypropylamino)acetate group (HOCH2CH2CH2NHCH2COOR). The resultant conjugated compound forms a 1:1 host-guest complex with a dimeric zinc porphyrin tweezer, which exhibits exciton-coupled bisignate CD spectrum centered around the 420-nm porphyrin Soret band due to induced helicity between the two porphyrins in the complex. The absolute configurations of the alpha-stereogenic center is then determined by comparison of the sign of the observed CD exciton couplet of the complex with that of the preferred porphyrin twist predicted by the Merck Molecular Force Field (MMFFs) method.

Isolation and characterization of a lipoxygenase from Pseudomonas 42A2 responsible for the biotransformation of oleic acid into ( S )-( E )-10-hydroxy-8-octadecenoic acid.

The isolation of a new lipoxygenase-like (LOX-like) enzyme from Pseudomonas 42A2 and its characterization is described. The enzyme, located in the periplasm of the cell, which contained 0.55 mol of Fe2+ per mol of protein, is monomeric and has a molecular mass of 45 kDa. In the presence of oxygen, the enzyme converts oleic acid into (E)-10-hydroperoxy-8-octadecenoic acid (HPOD), which decomposes to the corresponding (E)-10-hydroxy-8-octadecenoic acid (HOD). The absolute configuration of this acid was determined as S on the basis of exciton-coupled CD data, and specific rotation and NMR analysis of the corresponding p -bromobenzoate derivative. The reaction in vivo leads to the dihydroxy derivative (E)-7,10-dihydroxy-8-octadecenoic acid (DHOD), so that the three hydroxy-fatty acids can be isolated from the culture medium. The activity of the enzyme was optimal between 25 and 30 degrees C and 44% of its activity still remained at 55 degrees C. Its optimal pH is 8.5-9; and the presence of magnesium ions increased LOX activity by 1.5. The activity of the LOX is highest in unsaturated fatty acids containing double bonds in position 9 (oleic, linoleic and linolenic acids), linoleic acid being preferred (100% activity) over linolenic (60.4%) and oleic acids (46%). However, kinetic studies showed that the affinity of the enzyme is similar for the three substrates.

Assignment of absolute configuration of chiral carboxylic acids via exciton-coupled CD treatment: 4-phenylthioproline as a case study.

The 4-hydroxybenzoate chromophore was used as an exciton reporter group for the assignment of the absolute configuration of a chiral carboxylic acid of pharmaceutical interest, (-)-(2S,4S)-4-phenylthioproline, precursor of the ACE-inhibitor zofenopril. The nondegenerate coupling with the preexisting phenylthio chromophore was observed. A detailed conformational analysis, accomplished by means of (1)H-NMR NOESY and semiempirical PM3 computational methods, and quantitative CD calculations were necessary to substantiate the assignment based on a weak experimental couplet.

Chiral recognition by CD-sensitive dimeric zinc porphyrin host. 1. Chiroptical protocol for absolute configurational assignments of monoalcohols and primary monoamines.

A general microscale protocol for the determination of absolute configurations of primary amino groups or secondary hydroxyl groups linked to a single stereogenic center is described. The chiral substrates are linked to the achiral trifunctional bidentate carrier molecule (3-aminopropylamino)acetic acid (1, H(2)NCH(2)CH(2)CH(2)NHCH(2)COOH) and the resultant conjugates are then complexed with dimeric zinc porphyrin host 2 giving rise to 1:1 host/guest sandwiched complexes. These complexes exhibit exciton-coupled bisignate CD spectra due to stereodifferentiation leading to preferred porphyrin helicity. Since the chiral sense of twist between the two porphyrins in the complex is dictated by the stereogenic center of the substrate, the sign of the couplet determines the absolute configuration at this center. The twist of the porphyrin tweezer in the complex can be predicted from the relative steric sizes of the groups flanking the stereogenic center, such that the bulkier group protrudes from the complex sandwich. In certain alpha-hydroxy esters and alpha-amino esters, electronic factors and hydrogen bonding govern the preferred conformation of the complex, and hence the CD spectra.

Solving challenging bioorganic problems by exciton coupled CD

Abstract

Pairwise additivity in exciton-coupled CD curves of multichromophoric systems

Pairwise additivity in exciton-coupled CD curves of multichromophoric systems