Restricting the conformational heterogeneity of RNA by specific incorporation of 8-bromoguanosine

In an effort to reduce the conformational heterogeneity of RNA, the modified nucleobase 8-bromoguanosine (8BrG) was introduced into oligonucleotides having the hairpin tetraloop motif YNMG (Y = U or C and M = C or A). Purine nucleobases with bromine at position eight are known to preferentially adopt the syn conformation as nucleosides. The hairpin tetraloop motif YNMG was chosen as a model system because it has a syn guanosine at position four of the loop that is essential for thermodynamic stability. Thermodynamic and structural characterization of modified oligonucleotides with the hairpin sequences UUCG, CGCG, and CGAG by UV-melting and NMR spectroscopy revealed that 8BrG substitution has a small effect upon the hairpin conformation, while the duplex conformation is strongly destabilized (DeltaDeltaG degrees 37 approximately +4.7 kcal mol-1), thus inhibiting dimerization. These results support a model in which 8BrG substitution shifts the hairpin-duplex equilibrium constant toward the hairpin conformation by destabilizing the duplex. This methodology should be useful for limiting conformational heterogeneity in large RNAs, with potential applications in structural biology and enzymology.     

Organometallic ruthenium(II) diamine anticancer complexes: arene-nucleobase stacking and stereospecific hydrogen-bonding in guanine adducts

Organometallic ruthenium(II) arene anticancer complexes of the type [(eta(6)-arene)Ru(II)(en)Cl][PF(6)] (en = ethylenediamine) specifically target guanine bases of DNA oligomers and form monofunctional adducts (Morris, R., et al. J. Med. Chem. 2001). We have determined the structures of monofunctional adducts of the "piano-stool" complexes [(eta(6)-Bip)Ru(II)(en)Cl][PF(6)] (1, Bip = biphenyl), [(eta(6)-THA)Ru(II)(en)Cl][PF(6)] (2, THA = 5,8,9,10-tetrahydroanthracene), and [(eta(6)-DHA)Ru(II)(en)Cl][PF(6)] (3, DHA = 9,10-dihydroanthracene) with guanine derivatives, in the solid state by X-ray crystallography, and in solution using 2D [(1)H,(1)H] NOESY and [(1)H,(15)N] HSQC NMR methods. Strong pi-pi arene-nucleobase stacking is present in the crystal structures of [(eta(6)-C(14)H(14))Ru(en)(9EtG-N7)][PF(6)](2).(MeOH) (6) and [(eta(6)-C(14)H(12))Ru(en)(9EtG-N7)][PF(6)](2).2(MeOH) (7) (9EtG = 9-ethylguanine). The anthracene outer ring (C) stacks over the purine base at distances of 3.45 A for 6 and 3.31 A for 7, with dihedral angles of 3.3 degrees and 3.1 degrees, respectively. In the crystal structure of [(eta(6)-biphenyl)Ru(en)(9EtG-N7)][PF(6)](2).(MeOH) (4), there is intermolecular stacking between the pendant phenyl ring and the purine six-membered ring at a distance of 4.0 A (dihedral angle 4.5 degrees). This stacking stabilizes a cyclic tetramer structure in the unit cell. The guanosine (Guo) adduct [(eta(6)-biphenyl)Ru(en)(Guo-N7)][PF(6)](2).3.75(H(2)O) (5) exhibits intramolecular stacking of the pendant phenyl ring with the purine five-membered ring (3.8 A, 23.8 degrees) and intermolecular stacking of the purine six-membered ring with an adjacent pendant phenyl ring (4.2 A, 23.0 degrees). These occur alternately giving a columnar-type structure. A syn orientation of arene and purine is present in the crystal structures 5, 6, and 7, while the orientation is anti for 4. However, in solution, a syn orientation predominates for all the biphenyl adducts 4, 5, and the guanosine 5'-monophosphate (5'-GMP) adduct 8 [(eta(6)-biphenyl)Ru(II)(en)(5'-GMP-N7)], as revealed by NMR NOE studies. The predominance of the syn orientation both in the solid state and in solution can be attributed to hydrophobic interactions between the arene and purine rings. There are significant reorientations and conformational changes of the arene ligands in [(eta(6)-arene)Ru(II)(en)(G-N7)] complexes in the solid state, with respect to those of the parent chloro-complexes [(eta(6)-arene)Ru(II)(en)Cl](+). The arene ligands have flexibility through rotation around the arene-Ru pi-bonds, propeller twisting for Bip, and hinge-bending for THA and DHA. Thus propeller twisting of Bip decreases by ca. 10 degrees so as to maximize intra- or intermolecular stacking with the purine ring, and stacking of THA and DHA with the purine is optimized when their tricyclic ring systems are bent by ca. 30 degrees, which involves increased bending of THA and a flattening of DHA. This flexibility makes simultaneous arene-base stacking and N7-covalent binding compatible. Strong stereospecific intramolecular H-bonding between an en NH proton oriented away from the arene (en NH(d)) and the C6 carbonyl of G (G O6) is present in the crystal structures of 4, 5, 6, and 7 (average N...O distance 2.8 A, N-H...O angle 163 degrees ). NMR studies of the 5'-GMP adduct 8 provided evidence that en NH(d) protons are involved in strong H-bonding with the 5'-phosphate and O6 of 5'-GMP. The strong H-bonding from G O6 to en NH(d) protons partly accounts for the high preference for binding of [(eta(6)-arene)Ru(II)en](2+) to G versus A (adenine). These studies suggest that simultaneous covalent coordination, intercalation, and stereospecific H-bonding can be incorporated into Ru(II) arene complexes to optimize their DNA recognition behavior, and as potential drug design features.     

Preparation and conformation of octaethylbiphenylene

Dimerization of tetraethylbenzyne (generated by reaction of 1, 2-dibromo-3,4,5,6-tetraethylbenzene (8) with 1 equiv of BuLi) afforded in low yield octaethylbiphenylene (3), together with a major product which was characterized as 2,3,4,5,3',4', 5'-heptaethyl-2'-vinylbiphenyl (9). X-ray diffraction indicates that biphenylene 3 adopts in the crystal a conformation of approximate C(2)(h )()symmetry with the ethyl groups within each phenylene ring arranged in an alternated up-down fashion. Notably, pairs of vicinal ethyl groups located at peri positions are oriented in a syn arrangement in the crystal. Low temperature NMR spectroscopy is consistent with the presence in solution of either the crystal conformation or a fully alternated conformation lacking any syn interaction. Molecular mechanics (MM3), semiempirical (AM1, PM3), and ab initio calculations indicate that the crystal conformation is a high energy form, and that the lowest energy conformation is the fully alternated form. The topomerization barrier of the methylene protons of the ethyl groups of 3 is 9.4 +/- 0.1 kcal mol(-)(1), which is between the rotational barriers of 8 and 1,2,3, 4-tetraethylbenzene 7 (9.9 +/- 0.1 and 8.2 +/- 0.1 kcal mol(-)(1), respectively). The similarity in rotational barriers suggests that a given tetraethylphenylene subunit does not markedly affect the rotational barrier of the ethyl groups of the other subunit.     

Novel and unusual triterpene from Black Cohosh. Determination of structure of 9,10-seco-9,19-cyclolanostane xyloside (cimipodocarpaside) by NMR, IR and Raman spectroscopy and DFT calculations

A new triterpene xyloside, designated cimipodocarpaside was isolated from a Black Cohosh (Actea racemosa L.) extract and its structure was elucidated by means of 1H, 13C NMR, IR and Raman spectroscopy supported by B3LYP/6-31G** calculations. The vibrational spectra were interpreted using the PED analysis of 273 fundamentals. Its structure comprises four condensed rings A-D which are 6, 7, 6, and 5-membered, respectively. An oxiirane ring is located in the side chain and a xylose moiety is attached to the A-ring. Comparison of the experimental 13C NMR data with the theoretical chemical shifts of 24S- and 24R-cimipodocarpaside isomers revealed that the isolated compound has the 24S-configuration. Combined spectroscopic and computational studies enabled the determination of the structure of cimipodocarpaside as (24S)-3β-hydroxy-24,25-oxiirane-16,23-dione-9,10-seco-9,19-cyclolanost-7(8),9(11),10(19)-trien-3-O-β-D-xylopyranoside. Triterpenes with 7-membered ring were thus far isolated from only Actea podocarpa DC. plants. This is the first report on the isolation of such a compound from Black Cohosh.     

Conformational studies by dynamic NMR. 90. Structure and stereodynamics of the rotamers of di- and tri-alpha-naphthylphenyl derivatives

The crystal structure of 1,3,5-tris(4-methylnaphth-1-yl)benzene, 1, shows one naphthyl substituent in an anti relationship to the other two. On the other hand, low temperature (-70 degrees C) (1)H NMR spectra in solution show the presence of a second rotational conformer (rotamer) having all the three naphthyl substituents in a syn relationship. The interconversion barrier between the anti (77%) and syn (23%) rotamers of 1 was determined by line shape simulation of the temperature-dependent NMR spectra (Delta G(++) = 12.1 kcal mol(-1)). In the analogous disubstituted meta and paraderivatives, that is, 1,3- and 1,4-bis(4-methylnaphth-1-yl)benzene (2 and 3, respectively), the presence of both the anti and syn rotamers was also detected by low-temperature NMR spectroscopy. In the latter compounds, the proportions of the anti and syn forms are nearly equal, and the corresponding anti to syn interconversion barriers were found to be lower (11.4 and 11.1(5) kcal mol(-1), respectively) than those of the trisubstituted derivative 1.     

Studies of some monocyclic and bicyclic arylacetonitriles

The high-resolution (1)H, (13)C, (1)H-(1)H COSY and (1)H-(13)C COSY NMR spectra have been recorded in CDCl(3) for arylacetonitriles 1-12 and analyzed. The arylacetonitriles 3-7 exist in two isomeric forms E (methyl group is anti to cyano group) and Z (the methyl group is syn to cyano group) in solution. Normal chair conformation with equatorial orientations of phenyl rings at C-2 and C-6 for monocyclic nitriles 1 and 2, epimeric chair structure EC (axial configuration of methyl group at C-3) for both the E and Z isomers of arylacetonitrile derivatives (3-7) and a distorted boat form, B(3), for the N-acylacetonitrile derivatives (8-10) have been proposed based on NMR data. The bicyclic nitriles 11 and 12 exist in twin chair conformations in solution. DFT calculations and chemical shifts also support these conformations. Geometry optimizations for 1-12 were carried out according to density functional theory using B3LYP/6-31G(d,p) basis set and for 1 and 8 the theoretical geometrical parameters have been compared with those of single crystal measurements.     

Probing general base catalysis in the hammerhead ribozyme

Recent structural and computational studies have shed new light on the catalytic mechanism and active site structure of the RNA cleaving hammerhead ribozyme. Consequently, specific ribozyme functional groups have been hypothesized to be directly involved in general/acid base catalysis. In order to test this hypothesis, we have developed an affinity label to identify the functional general base in the S. mansoni hammerhead ribozyme. The ribozyme was reacted with a substrate analogue bearing a 2'-bromoacetamide group in place of the nucleophilic 2'-hydroxyl group which would normally be deprotonated by a general base. The electrophilic 2'-bromoacetamide group is poised to alkylate the general base, which is subsequently identified by footprinting analysis. Herein, we demonstrate alkylation of N1 of G12 in the hammerhead ribozyme in a pH and [Mg(2+)] dependent manner that is consistent with the native cleavage reaction. These results provide substantial evidence that deprotonated N1 of G12 functions directly as a general base in the hammerhead ribozyme; moreover, our experiments provide evidence that the pKa of G12 is perturbed downward in the context of the active site structure. We also observed other pH-independent alkylations, which do not appear to reflect the catalytic mechanism, but offer further insight into ribozyme conformation and structure.     

Polyethylated aromatic rings: conformation and rotational barriers of 1,2,3,4,5,6,7,8-octaethylanthracene, 1,2,3,4,6,7,8-heptaethylfluorene, and 1,2,3,4,5,6,7,8-octaethylfluorene

1,2,3,4,5,6,7,8-Octaethylanthracene (5), 1,2,3,4,6,7,8-heptaethylfluorene (7), and 1,2,3,4,5,6,7,8-octaethylfluorene (8) were synthesized by Friedel-Crafts ethylations of 9,10-dihydroanthracene and fluorene. MM3 calculations indicate that the two ethylated six-membered rings of 5 and 7 are conformationally independent. According to the calculations, two low-energy conformers of each compound are possible with the ethyl groups attached to the external aryl rings arranged in an alternated "up-down" orientation. MM3 calculations indicate that in the lowest energy conformation the central fluorene core of 8 adopts a twisted conformation to avoid repulsive steric interactions between the ethyls at the bay region. Two fully alternated up-down conformations are possible for 8, differing in the orientation ("in" or "out") of the ethyls in the bay region. MM3 calculations predict that the lowest energy conformer is the fully alternated "out" form of C(2)() symmetry. The rotational barriers of 5, 7, and 8 are in the 8.7-11.3 kcal mol(-1) range, the largest barrier corresponding to the more crowded octaethylfluorene 8. Anthracene 5 adopts in the crystal a conformation of approximate C(2)(h) symmetry with pairs of peri groups on the same edge of the molecule oriented syn. The conformations adopted in the crystal by 7 and 8 do not correspond to the calculated lowest energy form. In the conformation of 7 in the crystal the ethyl groups on the trisubstituted ring adopt the unusual all syn arrangement. Octaethylfluorene 8 adopts a conformation with a twisted central fluorene core but with a syn arrangement of a pair of vicinal ethyl groups.     

Chiral boron-bridged bisoxazoline (borabox) ligands: structures and reactivities of Pd and Cu complexes

Anionic boron-bridged bisoxazolines (borabox ligands) have been synthesized and characterized in their protonated forms. The ligands are tuneable over a wide range, allowing either alkyl or aryl substituents at the oxazoline rings and the central bridging boron atom. The structural parameters of this new ligand type have been investigated by X-ray analyses of palladium and copper complexes. Electronic properties have been studied by (13)C NMR spectroscopy and by DFT calculations on palladium allyl complexes and compared to those of analogous bisoxazoline (box) complexes. Borabox complexes are more electron-rich at the metal center than their neutral box congeners, and as a consequence of the longer bonds between the bridging atom and the oxazoline rings, their bite angles are larger. Palladium(II) complexes bearing an unsubstituted allyl ligand and homoleptic copper(II) complexes each possess an almost flat chelate ring. NMR analysis of a (1,3-diphenylallyl)(borabox)palladium complex showed a 92:8 mixture of (syn,syn) and (anti,syn) allyl isomers, in contrast with a previously reported box analogue that existed exclusively in the (syn,syn) form. Comparison of the corresponding crystal structures revealed that the distance between the bisoxazoline and the allyl ligand in the borabox complex is shorter. In the copper-catalyzed allylic oxidation of cyclohexene and cyclopentene with tert-butyl perbenzoate, borabox ligands gave results similar-and in some cases superior-to those obtained with analogous box ligands.     

Using diffusion NMR to characterize guanosine self-association: insights into structure and mechanism

This paper presents results from a series of pulsed field gradient (PFG) NMR studies on lipophilic guanosine nucleosides that undergo cation-templated assembly in organic solvents. The use of PFG-NMR to measure diffusion coefficients for the different aggregates allowed us to observe the influences of cation, solvent and anion on the self-assembly process. Three case studies are presented. In the first study, diffusion NMR confirmed formation of a hexadecameric G-quadruplex [G 1](16)4 K(+)4 pic(-) in CD(3)CN. Furthermore, hexadecamer formation from 5'-TBDMS-2',3'-isopropylidene G 1 and K(+) picrate was shown to be a cooperative process in CD(3)CN. In the second study, diffusion NMR studies on 5'-(3,5-bis(methoxy)benzoyl)-2',3'-isopropylidene G 4 showed that hierarchical self-association of G(8)-octamers is controlled by the K(+) cation. Evidence for formation of both discrete G(8)-octamers and G(16)-hexadecamers in CD(2)Cl(2) was obtained. The position of this octamer-hexadecamer equilibrium was shown to depend on the K(+) concentration. In the third case, diffusion NMR was used to determine the size of a guanosine self-assembly where NMR signal integration was ambiguous. Thus, both diffusion NMR and ESI-MS show that 5'-O-acetyl-2',3'-O-isopropylidene G 7 and Na(+) picrate form a doubly charged octamer [G 7](8)2 Na(+)2 pic(-) 9 in CD(2)Cl(2). The anion's role in stabilizing this particular complex is discussed. In all three cases the information gained from the diffusion NMR technique enabled us to better understand the self-assembly processes, especially regarding the roles of cation, anion and solvent.     

Synthesis,Coordination Chemistry and Bonding of Strong N‐Donor Ligands Incorporating the 1H‐Pyridin‐(2E)‐Ylidene (PYE) Motif

A range of N‐donor ligands based on the 1H‐pyridin‐(2E)‐ylidene (PYE) motif have been prepared, including achiral and chiral examples. The ligands incorporate one to three PYE groups that coordinate to a metal through the exocyclic nitrogen atom of each PYE moiety, and the resulting metal complexes have been characterised by methods including single‐crystal X‐ray diffraction and NMR spectroscopy to examine metal–ligand bonding and ligand dynamics. Upon coordination of a PYE ligand to a proton or metal‐complex fragment, the solid‐state structures, NMR spectroscopy and DFT studies indicate that charge redistribution occurs within the PYE heterocyclic ring to give a contribution from a pyridinium–amido‐type resonance structure. Additional IR spectroscopy and computational studies suggest that PYE ligands are strong donor ligands. NMR spectroscopy shows that for metal complexes there is restricted motion about the exocyclic C? N bond, which projects the heterocyclic N‐substituent in the vicinity of the metal atom causing restricted motion in chelating‐ligand derivatives. Solid‐state structures and DFT calculations also show significant steric congestion and secondary metal–ligand interactions between the metal and ligand C? H bonds.     

A comparative study of the single crystal X-ray determination and molecular modelling of the binding of oligomycin to ATP Synthase

Recently published X-ray structures of three common forms, A, B and C, of oligomycin, including absolute configurations, are investigated to examine their binding to ATP Synthase. The X-ray studies reveal regions with differences in three-dimensional structure and hydrogen bonding propensity between the oligomycins, which may be associated with their potential to bind to sites on ATP Synthase. Computational docking studies carried out using MOE with the X-ray structures and an homology model of the F_O domain of ATP Synthase from Escherichia coli, are used to derive an induced fit pocket. Docking of all oligomycins to this pocket indicate that the B and C forms bind more tightly than the A form. Consideration of the single crystal X-ray data alone indicate the B form may be the best inhibitor and that O(24) is the most important ligating group for binding, this is supported by the docking data. The latter reveals Asn214 and other key proton translocating residues to be the main residues contacted by the inhibitor. These data allow the binding modes of different forms of oligomycin to be deduced from X-ray single crystal data supported by molecular modelling and computational docking studies.     

New Spirostaphyiotrichins from the Mutant Strain P 84 of Staphylotrichum coccosporum

From a mutant strain of S. coccosporum, the new spirostaphylotrichins E ( 2 ), F( 3 ), G ( 4 or 5 ), H ( 5 or 4 ), I ( 6 ), K ( 7 ), L ( 8 ), M ( 9 ), and S ( 10 ) have been isolated. Their structures have been elucidated by spectroscopic methods (UV, IR, ¹H? NMR, ¹³C? NMR, and MS), chemical transformations, and X-ray analysis ( 3 and 7 ).     

A lead-filled G-quadruplex: insight into the G-Quartet's selectivity for Pb(2+) over K(+)

The lipophilic nucleoside, G 1, extracts Pb(2+) picrate from water into organic solvents to give structures based on the hydrogen-bonded G-quartet. Crystal structures indicate important differences between (G 1)(8)-Pb(2+) and (G 1)(8)-K(+). The divalent Pb(2+) templates a smaller G(8) cage than does K(+), as judged by the M-O6 bond length, O6-O6 diagonal distance, and inter-tetramer separation. The more compact Pb(2+) octamer correlates with NMR data indicating that N2-N7 hydrogen bonds in (G 1)(8)-Pb(2+) are kinetically more stable than in (G 1)(8)-K(+).     

Synthesis of the arachno-4-CB(8)H(12)(2)(-) monocarbaborane dianion and NMR/computational studies of the fluxional processes observed in the isoelectronic nine-vertex arachno anions: arachno-4-CB(8)H(12)(2)(-), arachno-4-CB(8)H(13)(-), and arachno-4-SB(8)H(11)(-)

The new monocarbaborane dianion, arachno-4-CB(8)H(12)(2)(-) has been synthesized from the reaction of arachno-4-CB(8)H(14) with 2 equiv of NaH in polar solvents. DFT/GIAO computations at the B3LYP/6-311G//B3LYP/6-311G level, in conjunction with 1D and 2D NMR spectroscopic studies, have confirmed that the dianion results from deprotonation of both the endo-CH and one bridging hydrogen of the parent arachno-4-CB(8)H(14). While the DFT calculations indicate that a C(1) symmetric structure is lowest in energy, the experimental solution NMR data are consistent with the dianion having a C(s)() symmetric structure, thus suggesting that it is fluxional in solution. Transition state calculations located a low-energy pathway with an activation energy of only 2.7 kcal/mol that allows the migration of the bridging hydrogen between the two enantiomeric forms of the dianion. The process can occur by a single-step, simple rotation through a transition state structure containing a -BH(2) group at the B7 boron. Averaging the calculated (11)B NMR chemical shifts of the resonances for those atoms in the static enantiomeric structures that become equivalent by this fluxional process then gives excellent agreement with the solution NMR data. Transition state calculations of the fluxional behavior previously observed for the isoelectronic arachno-4-CB(8)H(13)(-) and arachno-4-SB(8)H(11)(-) monoanions have likewise revealed related low-energy (0.3 and 5.0 kcal/mol, respectively) rearrangement mechanisms involving the simultaneous rotation of three hydrogens (two bridging and one -BH(2)) through a C(s)() symmetry transition state containing three -BH(2) groups.     

Cytotoxic sterols from marine-derived fungus Pennicillium sp

A new sterol, ergosta-8(14), 22-diene-3,5,6,7-tetraol(3beta, 5alpha, 6beta, 7alpha, 22E) (1), together with four known sterols ergosta-8(9), 22-diene-3,5,6,7-tetraol (3beta, 5alpha, 6beta, 7alpha, 22E) (2), 5alpha,8alpha-epidioxy-24(S)-methylcholesta-6,22-diene-3beta-ol (3), 5alpha,8alpha-epidioxy-24(S)-methylcholesta-6,9(11), 22-triene-3beta-ol (4), 3beta,5alpha,9alpha-trihydroxyergosta-7,22-diene-6-one (5) was isolated from marine fungus Pennicillium sp. Their structures were determined based on chemical analysis and spectral methods (IR, 1D and 2D NMR, HR-FAB-MS). Compounds 1-5 were evaluated for cytotoxicity against human liver cancer cell (Hep G), and most of them exhibited potent activity. Compound 1 display the highest potency with IC50 values 10.4 microg mL-1.     

NMR-based reappraisal of the coordination of a metal ion at the pro-Rp oxygen of the A9/G10.1 site in a hammerhead ribozyme

In the identification of a metal-binding site within enzymes, kinetic analyses based on thio-effects and Cd(2+)-rescues are widely used. In those analyses, kinetic studies using a phosphorothioate have been discussed on the premise that the substitution by a sulfur atom does not change the conformation of a ribozyme. However, our present NMR structural analysis demonstrates the change of the conformation at the metal-binding site by Rp-sulfur but not by Sp-sulfur substitution and warns against incautious interpretations of thio-effects and rescue phenomena in kinetic studies using a phosphorothioate. Our analysis further demonstrates that, in solution, a Cd(2+) ion can interact with an Rp-phosphorothioate (in support of the controversial McKay's structure, Nature 1994, 372, 68-74) and with an Sp-phosphorothioate (in support of the controversial Scott's structure, Cell 1995, 81, 991-1002) at the metal-binding A9/G10.1 site and that, in the former case, the bound Cd(2+) ion can return the ribozyme to an active conformation and rescue its enzymatic activity.     

Tris(arylmethyl) derivatives of 1,3,5-trimethoxy- and 1,3,5-triethylbenzene

The hexasubstituted benzenes 7 and 9b were synthesized starting from 3 and 8b, respectively. In the crystal, 9b adopts the fully alternated conformation with all arylmethyl groups oriented syn.     

meso-Trifluoromethyl-substituted expanded porphyrins

A series of meso-trifluoromethyl-substituted expanded porphyrins, including N-fused [24]pentaphyrin 3, [28]hexaphyrin 4, [32]heptaphyrin 5, [46]decaphyrin 6, and [56]dodecaphyrin 7, were synthesized by means of an acid-catalyzed one-pot condensation reaction of 2-(2,2,2-trifluoro-1-hydroxyethyl)pyrrole (1) as the first examples bearing meso-alkyl substituents. Besides these products, porphyrin 2 and two calix[5]phyrins 8 and 9 were also obtained. [28]Hexaphyrin 4 was quantitatively oxidized to [26]hexaphyrin 14 with MnO(2). These expanded porphyrins have been characterized by mass spectrometry, (1)H and (19)F NMR spectroscopy, and UV/Vis spectroscopy. The single-crystal structures have been determined for 3, 4, 6, 7, and 14. The N-fused [24]pentaphyrin 3 displays a distorted structure containing a tricyclic fused moiety that is similar to those of meso-aryl-substituted counterparts, whereas 8 and 9 are indicated to take roughly planar conformations with an inverted pyrrole opposite to the sp(3)-hybridized meso-carbon atom. Both [28]- and [26]hexaphyrins 4 and 14 have figure-of-eight structures. Solid-state structures of the decaphyrin 6 and dodecaphyrin 7 are remarkable, exhibiting a crescent conformation and an intramolecular two-pitch helical conformation, respectively.