Orientation and Restricted Rotation of Lopsided Aromatic Ligands. Octahedral Complexes Derived from cis-RuCl(2)(Me(2)SO)(4)

The solution and solid state structures of two octahedral Ru(II) complexes, cis,cis,cis-RuCl(2)(Me(2)SO)(2)(py)(Me(3)Bzm) (Me(3)Bzm = 1,5,6-trimethylbenzimidazole, py = pyridine) (1) and cis,cis,cis-RuCl(2)(Me(2)SO)(2)(Me(3)Bzm)(2) (2), were compared. 2, the subject of a preliminary report, is described in more detail here. 1 has two possible geometric isomers with py trans to Cl in one (position "a") and trans to Me(2)SO in the other (position "b"), Me(3)Bzm occupying the other position in each isomer. The X-ray structure of 1 revealed that py is at "a". Since Me(3)Bzm is lopsided, each Me(3)Bzm has two possible orientations related by a rotation of approximately 180 degrees about the Ru-N3 bond; there are two possible atropisomers for each geometric isomer of 1 and four for 2. For 1, the solid state structure shows that Me(3)Bzm adopts the orientation with H2 (H on C between the two N's) pointing between the two cis Cl ligands, the same disposition as Me(3)Bzm "b" in 2 in the solid. For 1, the py signals (two broad py alpha and beta signals, a sharp gamma signal) in CDCl(3) show that py "a" is rotating on the NMR time scale and that only one atropisomer is present. This interpretation was supported by ROESY and EXSY (1)H NMR spectra. The (1)H NMR shift pattern and the NOE data can be understood best if Me(3)Bzm "b" remains primarily in the orientation found in the solid. The solution data for 1, with the nonlopsided and sterically less demanding py ligand, provide insight into the more complicated properties of 2. For 2, there is a marked dispersion of (1)H NMR signals of Me(3)Bzm "a" between the two atropisomers, which have nearly equal stability. One atropisomer is a head-to-head (HH) and the other a head-to-tail (HT) species. Me(3)Bzm "a" flips between the two species. Thus, ligand "a" is fluxional in both complexes. The dispersion of Me(3)Bzm "a" signals is due to the effect of Me(3)Bzm "b" anisotropy. For 1 and both atropisomers of 2, Me(3)Bzm "b" prefers one orientation, which appears to be the most hindered orientation. We postulate that the H2 of Me(3)Bzm "b" is electrostatically attracted to the two cis halides, accounting for this surprising result. Crystallographic details for 1 are as follows: C(19)H(29)Cl(2)N(3)O(2)RuS(2), P2(1)/c, a = 10.947(1) ?, b = 9.046(1) ?, c = 24.221(2) ?, D(calcd) = 1.580 g cm(-)(3), Z = 4, R = 0.026 for 4627 independent reflections.     

Tuning the rotational behavior of lopsided heterocyclic nitrogen ligands (L) in octahedral cis-[Ru(bpy)2(L)2](PF6)2 complexes. A variable-temperature 1H NMR study

In this paper are presented the syntheses, characterizations, and dynamic solution behaviors of three cis-[Ru(bpy)2(L)2] (bpy = 2,2'-bipyridine) complexes, 1-3, in which L represents the monodentate ligands 1-methylimidazole (MeIm), 1,2-dimethylimidazole (Me2Im), and 1-methylbenzimidazole (MeBim), respectively. Because of their different steric properties, these three monodentate ligands yield complexes that show quite different fluxional behaviors in solution. These behaviors are studied with several 1H NMR techniques at various temperatures between -95 and degrees C. The 1H NMR spectra of 1, which has the smallest monodentate ligand of the three used, indicate the complex to be in fast exchange (i.e., the imidazoles rotate around their Ru-N axes) at all recording temperatures. The sterically more demanding ligands, Me2Im and MeBim, in 2 and 3, respectively, are in fast exchange at 55 degrees C and in slow exchange at low temperatures, showing three different atropisomers: two head-to-tail (HT) isomers and one head-to-head (HH) isomer. The newly synthesized bidentate ligand 1,2-bis-(1-methyl-2-benzimidazolyl)ethane (mdbz) forms the complex cis-[Ru(bpy)2(mdbz)](PF6)2 (4), in which the two benzimidazole moieties are constrained and relatively fixed. The two tethered benzimidazoles in 4 cannot rotate around their Ru-N axes, and therefore 4 is a good model for the main HT isomer of 3.     

Structural characterization of the picket fence (TpivPP) porphyrins Co(TpivPP), Co(TpivPP)(NO2)(1-MeIm), and Co(TpivPP)(NO2)(1,2-Me2Im)

The compounds Co(TpivPP) (1), Co(TpivPP)(NO2)(1-MeIm) (2), and Co(TpivPP)(NO2)(1,2-Me2Im) (3) have been synthesized (TpivPP = meso-tetrakis(alpha, alpha, alpha, alpha-o-pivalamidophenyl)porphyrinato dianion), and their structures have been determined with single-crystal X-ray diffraction methods. 1: a = 17.578(1) A, b = 17.596(1) A, c = 20.639(1) A, beta = 115.03(1) degrees, P2(1)/c, Z = 4, T = -120 degrees C. 2: a = 18.522(4) A, b = 18.942(4) A, c = 18.177(4) A, beta = 90.68(3) degrees, C2/c, Z = 4, T = -70 degrees C. 3: a = 18.998(4) A, b = 19.187(4) A, c = 18.000(4) A, beta = 90.96(3) degrees, C2/c, Z = 4, T = -120 degrees C. Compounds 2 and 3 have crystallographically imposed 2-fold axes. In 2 and 3, which represent R-state (relaxed) and T-state (tense) models, respectively, for hemoglobin, the NO2 ligand is bound on the "picket" side to the Co atom, and either 1-MeIm (for 2) or 1,2-Me2Im (for 3) is bound to the Co atom at the sixth coordination site on the sterically unhindered side of the molecule. The average deviations of atoms from the 24-atom porphyrin core are 0.031, 0.129, and 0.117 A for 1, 2, and 3, respectively. The Co atom is -0.043(1) A out of the mean 24-atom porphyrin plane toward the 1-MeIm ligand in 2 and -0.089(1) A out of the plane toward the 1,2-Me2Im ligand in 3. The bonds of both axial ligands in the R-state model 2, 1.898(4) A for Co-N(O2) and 1.995(4) A for Co-N(base), are shorter than the corresponding bonds in the T-state model 3, 1.917(4) A for Co-N(O2) and 2.091(4) A for Co-N(base).     

Imprinting structural information from a GpG ligand into the configuration of a chiral diamine ligand through second-sphere communication in platinum(II) complexes

Cisplatin forms the cis-Pt(NH3)2(d(GpG)) cross-link with DNA. We have recently created novel d(GpG) conformations by using "retro models" (complexes having bulky carrier ligands designed to slow d(GpG) dynamic motion). Our results define four conformer classes: HH1, HH2, delta HT1, and delta HT2, with a head-to-head or head-to-tail base orientation and a phosphodiester backbone with a normal (1) or opposite (2) propagation direction. Moreover, each G residue can be syn or anti, and the base canting can be left-handed (L) or right-handed (R). Thus, 32 variants of cis-Pt(NH3)2(d(GpG)) are conceivable, but the adduct is too dynamic to study. Thus far, by using retro models, we have obtained evidence for five variants with d(GpG) but only four with GpG. We therefore selected Me2DAPPt(GpG) complexes for study by 1H and 31P NMR spectroscopy, CD spectroscopy, and molecular mechanics and dynamics (MMD) calculations. Coordinated Me2DAP (N,N'-dimethyl-2,4-diaminopentane) has N, C, C, N chiral centers designated, for example, as R,R,R,R. This ligand has greater flexibility and more readily inverted N centers than ligands used previously in GpG retro models. One goal was to determine whether the GpG ligand can control the configuration of a carrier ligand. (R,R,R,R)-Me2DAPPt(GpG) forms the anti, anti HH1 R variant almost exclusively. Equal populations of the two possible linkage isomers of (S,R,R,R)-Me2DAPPt(GpG) are formed, both favoring the anti, anti HH1 R, variant; however, the isomer with the 5'-G cis to the S nitrogen has sharper signals, suggesting that interligand interactions are more favorable. Indeed, this linkage isomer was the major product of isomerization when (R,R,R,R)-Me2DAPPt(GpG) was kept at pH approximately 9.5 to allow N center equilibration. Steric clashes between the Me2DAP C-Me groups and the G O6 atoms found by MMD calculations appear to disfavor the HH1 conformer of (S,S,S,S)-Me2DAPPt(GpG) and (S,S,S,R)-Me2DAPPt(GpG) complexes. These two complexes have a significant population of the anti, syn delta HT1 conformer, as indicated by broad 1H NMR signals and by 31P NMR and CD data. Equilibration of (S,S,S,R)-Me2DAPPt(GpG) at pH 9.5 leads to a mixture of (S,S,S,S)-Me2DAPPt(GpG) and at least one isomer of (S,S,S,R)-Me2DAPPt(GpG). Thus, second-sphere communication (hydrogen bonding and steric interligand interactions) influences both GpG conformation and Me2DAP configuration.     

Head-to-head (HH) and head-to-tail (HT) conformers of cis-bis guanine ligands bound to the [Re(CO)3]+ core

We have prepared four complexes of the type [Re(guanine)(2)(X)(CO)(3)] (guanine = 9-methylguanine or 7-methylguanine, X = H(2)O or Br) in order to understand the factors determining the orientation of coordinated purine ligands around the [Re(CO)(3)](+) core. The 9-methylguanine ligand (9-MeG) was chosen as the simplest N(9) derivatized guanine, and 7-methylguanine (7-MeG) was chosen because metal binding to N(9) does not impose steric hindrance. Two types of structures have been elucidated by X-ray crystallography, an HH (head-to-head) and HT (head-to-tail) conformer for each of the guanines. All complexes crystallize in monoclinic space groups: [Re(9-MeG)(2)(H(2)O)(CO)(3)]ClO(4) (2) in P2(1)/n with a = 12.3307(10) A, b = 16.2620(14) A, c = 13.7171(11) A, and beta = 105.525(9) degrees, V = 2650.2(4) A(3), with the two bases in HT orientation and its conformer [Re(9-MeG)(2)(H(2)O)(CO)(3)]Br (3) in P2(1)/n with a = 15.626(13) A, b = 9.5269(5) A, c = 15.4078(13) A, and beta = 76.951(1) degrees, V = 2234.5(3) A(3), and the two bases in an HH orientation. Similarly, [Re(7-MeG)(2)(H(2)O)(CO)(3)]ClO(4) (4) crystallizes in P2(1)/c with a = 13.0708(9) A, b = 15.4082(7) A, c = 14.316(9) A, and beta = 117.236(7) degrees, V = 2563.5(3) A(3), and exhibits an HT orientation and [ReBr(7-MeG)(2)(CO)(3)] (5) in P2/c with a = 17.5117(9) A, b = 9.8842(7) A, c = 15.3539(1) A, and beta = 100.824(7) degrees, V = 2610.3(3) A(3), and shows an HH orientation. When crystals of any of these complex pairs are dissolved in D(2)O, the (1)H NMR spectrum shows a single peak for the H(8) resonance of the respective coordinated purine indicating a rapid equilibrium between HH and HT conformations in solution. DFT calculations simulating the rotation of one ligand around its Re-N bond showed energetic barriers of less than 8.7 kcal/mol. We find no hypochromic effect in the Raman spectrum of 3, which showed base stacking in the solid state. Neither steric interactions nor hydrogen bonding are important in determining the orientation of the ligands in the coordination sphere.     

Synthetic,structural and binding studies of the 4,6-dimethyldibenzothiophene complex [(eta(5)-C(5)Me(5))Ru(CO)(2)(eta(1)(S)-4,6-Me(2)DBT)]BF(4): toward an understanding of deep hydrodesulfurization

The synthesis of the first completely characterized transition-metal complex containing a sulfur-bound 4,6-dimethyldibenzothiophene (4,6-Me(2)DBT) ligand, [CpRu(CO)(2)(eta(1)(S)-4,6-Me(2)DBT)]BF(4) (1) (Cp = eta(5)-C(5)Me(5)), is reported. X-ray studies of 1 and its 4-methyldibenzothiophene and dibenzothiophene analogues, [CpRu(CO)(2)(eta(1)(S)-4-MeDBT)]BF(4) (2) and [CpRu(CO)(2)(eta(1)(S)-DBT)]BF(4) (3), show that the Ru-S bond distances increase in the order, 3 < 2 < 1. Equilibrium studies on the series of [CpRu(CO)(2)(eta(1)(S)-DBTh)](+) compounds, where DBTh = DBT, 4-MeDBT, 4,6-Me(2)DBT, and 2,8-Me(2)DBT, show that the relative binding strengths of the dibenzothiophene ligands increase in the order 4,6-Me(2)DBT (1) < 4-MeDBT (20.2(1)) < DBT (62.7(6)) < 2,8-Me(2)DBT (223(3)). These results are the first to quantify the steric effect of 4- and 6-methyl groups on the sulfur-coordinating ability of dibenzothiophenes to transition-metal centers. They are also consistent with the proposal that 4- and 6-methyl groups reduce the coordination of dibenzothiophenes to active metal sites on hydrodesulfurization catalysts, which could account for the slow rate of 4-MeDBT and 4,6-Me(2)DBT hydrodesulfurization in petroleum feedstocks.     

Understanding the orientation and dynamic motion of planar heterocyclic N-donor ligands by exploiting the symmetry properties of mixed-ligand mu-oxorhenium(V) dinuclear complexes

Factors influencing the orientation and dynamic motions of planar N-donor heterocyclic ligands (L) are of interest since such features have broad relevance in metallobiochemistry [Marzilli, L. G.; Marzilli, P. A.; Alessio, E. Pure Appl. Chem. 1998, 70, 961-968]. We found that mu-oxorhenium(V) dinuclear complexes [ReOCl2LsLt]-O-[ReOCl2LsLt] bearing either symmetrical (L = py = pyridine; 3,5-lut = 3,5-lutidine) or lopsided (L = Me3-Bzm = 1,5,6-trimethylbenzimidazole) cis L ligands are particularly useful for studying these factors. NMR data showed that terminal (Lt) and stacked (Ls) ligands were exchanged by approximately 180 degrees rotation about the Re-O-Re bond system. Such exchange occurred, however, between degenerate chiral conformers. Here we report a combined X-ray structural and solution NMR investigation of the AA + CC (racemic) and AC (meso) forms of two mixed-ligand mu-oxorhenium dimers that bear one lopsided and one symmetrical ligand on each Re atom, namely, Re2O3-Cl4(py)2(Me3Bzm)2 (1rac and 1meso) and Re2O3Cl4(3,5-lut)2(Me3Bzm)2 (2rac and 2meso). The presence of two different cis L ligands in 1 and 2 breaks the local symmetry at each Re atom, so that, in the racemic dimers, the exchange of terminal and stacked ligands leads to nondegenerate conformers. Overall, NMR data showed that the unsymmetrical dimers 1 and 2 undergo two dynamic processes contemporaneously, namely, 180 degrees rotation about the Re-N(py or 3,5-lut) bond and coupled rotation about the Re-O-Re/Re-N bonds. Both processes reach the slow exchange limit below -80 degrees C. Rotation of py in 1 occurs faster than that of 3,5-lut in 2; this difference is attributed to the higher steric demands of 3,5-lut compared to py. For both dimers NMR data provided compelling evidence of the preferred conformers in solution, including ligand orientations. The low-T solution structure of 1meso and 2meso is chiral, the same as that found in the solid state for 2meso, where the Me3Bzm on one Re atom is stacked with the 3,5-lut on the other Re atom. The remaining Me3Bzm and 3,5-lut, one on each Re atom, are both terminal. In solution the coupled Re-O-Re/Re-N rotations interconvert the two halves of each meso dimer to yield the same overall stable chiral conformation. For the racemic dimers, however, this process does not interconvert one enantiomer into the other, but instead interconverts two rotamers, R1 and R2, each of which is chiral. We found that, in the case of both 1rac and 2rac, the conformer with stacking symmetrical ligands (R1) is roughly 1 order of magnitude more stable than that with stacking Me3Bzm ligands (R2). Moreover, the solution conformation of R1 is the same as that found in the solid state of 1rac. Solution- and solid-state data indicate that the key interaction favoring the observed conformations is very likely the electrostatic attraction between the delta+ H2 atoms on the Me3Bzm ligands and the negative O and Cl groups in the core of the dimers. Finally, for both meso and racemic dimers we were also able to elucidate the preferred pathways of the coupled dynamic motions and establish that, very likely, the two halves of the dimers swing back and forth by approximately 130 degrees through the anti eclipsed form.     

Ligands rock & roll: stepwise twisting of two cis-coordinated lopsided N-heterocycles in an octahedral bis(2-phenylazopyridine)-ruthenium(II) complex with seven atropisomers

1H NMR data of alpha-[Ru(azpy)2(MeBim)2](PF6)2 (azpy=2-phenylazopyridine, MeBim=1-methylbenzimidazole), 2, revealed the presence of a total of seven atropisomers at -95 degrees C: three head-to-tail, HT, isomers (A, C, and D), and four head-to-head, HH, isomers which, due to the presence of an intrinsic C2 axis in the alpha-[Ru(azpy)2] moiety, are two sets of identical pairs (B/B and E/E). The NMR data of 2 represent a unique example of a coordination compound that shows a variable temperature (VT) behavior with more, well-defined steps of slow-to-fast exchange of its atropisomers. At 65 degrees C, all atropisomers are in fast exchange; on lowering the temperature the sharp signals first broaden (at room temperature) and consecutively split up into two sets of relatively sharp signals, in slow exchange, at about 0 degrees C (D, 40 %, and the coalesced signals of ABBCEE, 60 %). Upon further cooling, the set of peaks belonging to D remain sharp until the lowest recording temperatures. The signals of the other set of resonances, on the other hand, first broaden again and then separate into two sets of broad peaks (C/E/E and A) and one set of sharp peaks (B and B in fast exchange); on lowering the temperature even more, these signals broaden once again and finally, at -95 degrees C, are split up into a total of four sets of signal (A, B/B, C, and E/E). At low temperatures, ROESY experiments revealed that atropisomerization occurs through the synchronous rotation of both MeBim ligands in the interconversion of the two "identical" HH atropisomers B and B, as well as in the interconversion between C and E/E. The HH rotamers B/B furthermore exhibit a slow-to-fast exchange atropisomerization behavior that is observed independently from the other dynamic processes in this compound. The versatile cis bifunctional binding of the DNA model bases (MeBim ligands) in 2 parallels the observation of alpha-[Ru(azpy)2Cl2] which shows extraordinarly high cytotoxicity against tumor cell lines.     

New synthetic routes to biscarbonylbipyridinerhenium(I) complexes cis,trans-[Re(X2bpy)(CO)2(PR3)(Y)n+ (X2bpy = 4,4'-X2-2,2'-bipyridine) via photochemical ligand substitution reactions, and their photophysical and electrochemical properties

Photochemical ligand substitution of fac-[Re(X2bpy)(CO)3(PR3)]+ (X2bpy = 4,4'-X2-2,2'-bipyridine; X = Me, H, CF3; R = OEt, Ph) with acetonitrile quantitatively gave a new class of biscarbonyl complexes, cis,trans[Re(X2bpy)(CO)2(PR3)(MeCN)]+, coordinated with four different kinds of ligands. Similarly, other biscarbonylrhenium complexes, cis,trans-[Re(X2bpy)(CO)2(PR3)(Y)]n+ (n = 0, Y = Cl-; n = 1, Y = pyridine, PR'3), were synthesized in good yields via photochemical ligand substitution reactions. The structure of cis,trans-[Re(Me2bpy)(CO)2[P(OEt)3](PPh3)](PF6) was determined by X-ray analysis. Crystal data: C38H42N2O5F6P3Re, monoclinic, P2(1/a), a = 11.592(1) A, b = 30.953(4) A, c = 11.799(2) A, V = 4221.6(1) A3, Z = 4, 7813 reflections, R = 0.066. The biscarbonyl complexes with two phosphorus ligands were strongly emissive from their 3MLCT state with lifetimes of 20-640 ns in fluid solutions at room temperature. Only weak or no emission was observed in the cases Y = Cl-, MeCN, and pyridine. Electrochemical reduction of the biscarbonyl complexes with Y = Cl- and pyridine in MeCN resulted in efficient ligand substitution to give the solvento complexes cis,trans-[Re(X2bpy)(CO)2(PR3)(MeCN)]+.     

The Co-CH(3) Bond in Imine/Oxime B(12) Models. Influence of the Orientation and Donor Properties of the trans Ligand As Assessed by FT-Raman Spectroscopy

Near-IR FT-Raman spectroscopy was used to probe the properties of three types of methyl imine/oxime B(12) model compounds in CHCl(3) solution. These types differ in the nature of the 1,3-propanediyl chain and were selected to test the influence of electronic and steric effects on the Co-CH(3) stretching (nu(Co)(-)(CH)()3) frequency, a parameter related to Co-C bond strength. For the first type studied, [LCo((DO)(DOH)pn)CH(3)](0/+) ((DO)(DOH)pn = N(2),N(2)(')-propane-1,3-diylbis(2,3-butanedione 2-imine 3-oxime)), nu(Co)(-)(CH)()3 decreased from 505 to 455 cm(-)(1) with stronger electron-donating character of the trans axial ligand, L, in the order Cl(-), MeImd, Me(3)Bzm, 4-Me(2)Npy, py, 3,5-Me(2)PhS(-), PMe(3), and CD(3)(-). This series thus allows the first assessment of the effect of negative axial ligands on nu(Co)(-)(CH)()3; these ligands (L = Cl(-), 3,5-Me(2)PhS(-), CD(3)(-)) span the range of trans influence. The CH(3) bending (delta(CH3)) bands were observed at 1171, 1159, and 1150/1105 cm(-)(1), respectively. The decrease in C-H stretching frequencies (nu(CH)) of the axial methyl suggests that the C-H bond strength decreases in the order Cl(-) > 3,5-Me(2)PhS(-) > CD(3)(-). This result is consistent with the order of decreasing (13)C-(1)H NMR coupling constants obtained for the axial methyl group. The trend of lower nu(Co)(-)(CH)()3 and nu(CH) frequencies and lower axial methyl C-H coupling constant for stronger electron-donating trans axial ligands can be explained by changes in the electronic character of the Co-C bond. The symmetric CH(3)-Co-CH(3) mode (nu(CH)()3(-)(Co)(-)(CH)()3) for (CH(3))(2)Co((DO)(DOH)pn) was determined to be 456 cm(-)(1) (421 cm(-)(1) for (CD(3))(2)Co((DO)(DOH)pn). The L-Co-CH(3) bending mode (delta(L)(-)(Co)(-)(CH)()3) was detected for the first time for organocobalt B(12) models; this mode, which is important for force field calculations, occurs at 194 cm(-)(1) for ClCo((DO)(DOH)pn)CH(3) and at 186 cm(-)(1) for (CH(3))(2)Co((DO)(DOH)pn. The nu(Co)(-)(CH)()3 frequencies were all lower than those reported for the corresponding cobaloxime type LCo(DH)(2)CH(3) (DH = monoanion of dimethylglyoxime) models for planar N-donor L. This relationship is attributed to a steric effect of L in [LCo((DO)(DOH)pn)CH(3)](+). The puckered 1,3-propanediyl chain in [LCo((DO)(DOH)pn)CH(3)](+) forces the planar L ligands to adopt a different orientation compared to that in the cobaloxime models. The consequent steric interaction bends the equatorial ligand toward the methyl group (butterfly bending); this distortion leads to a longer Co-C bond. In a second imine/oxime type, a pyridyl ligand is connected to the 1,3-propanediyl chain and oriented so as to minimize butterfly bending. The nu(Co)(-)(CH)()3 frequency for this new lariat model was close to that of pyCo(DH)(2)CH(3). In a third type, a bulkier 2,2-dimethyl-1,3-propanediyl group replaces the 1,3-propanediyl chain. The nu(Co)(-)(CH)()3 bands for two complexes with L = Me(3)Bzm and py were 2-5 cm(-)(1) lower in frequency than those of the corresponding [L(Co((DO)(DOH)pn)CH(3)](+) complexes. The decrease in the axial nu(Co)(-)(CH)()3 frequencies is probably due to the steric effect of the equatorial ligand. Thus, the nu(Co)(-)(CH)()3 frequency can be useful for investigating both steric and electronic influences on the Co-C bond.     

The metalla-Pinner reaction between Pt(IV)-bound nitriles and alkylated oxamic and oximic forms of hydroxamic acids

The nitrile ligands in the platinum(IV) complexes trans-[PtCl4(RCN)2] (R=Me, Et, CH2Ph) and cis/trans-[PtCl4(MeCN)(Me2SO)] are involved in a metalla-Pinner reaction with N-methylbenzohydroxamic acid (N-alkylated form of hydroxamic acid, hydroxamic form; F1), PhC(=O)N(Me)OH, to achieve the imino species [PtCl4[NH=C(R)ON(Me)C(=O)Ph]2 (1-3) and [PtCl4[NH=C(Me)ON(Me)C(=O)Ph](Me2SO)] (7), respectively. Treatment of trans-[PtCl4(RCN)2] (R=Me, Et) and cis/trans-[PtCl4(MeCN)(Me2SO)] with the O-alkylated form of a hydroxamic acid (hydroximic form), i.e. methyl 2,4,6-trimethylbenzohydroximate, 2,4,6-(Me3C6H2)C(OMe)=NOH (F2A), allows the isolation of [PtCl4[NH=C(R)ON=C(OMe)(2,4,6-Me3C6H2)]2] (5, 6) and [PtCl4[NH=C(Me)ON=C(OMe)(2,4,6-Me3C6H2)](Me2SO)] (8), correspondingly. In accord with the latter reaction, the coupling of nitriles in trans-[PtCl4(EtCN)2] with methyl benzohydroximate, PhC(OMe)=NOH (F2B), gives [PtCl4[NH=C(Et)ON=C(OMe)Ph]2] (4). The addition proceeds faster with the hydroximic F2, rather than with the hydroxamic form F1. The complexes 1-8 were characterized by C, H, N elemental analyses, FAB+ mass-spectrometry, IR, 1H and 13C[1H] NMR spectroscopies. The X-ray structure determinations have been performed for both hydroxamic and hydroximic complexes, i.e. 2 and 6, indicating that the imino ligands are mutually trans and they are in the E-configuration.     

Stepwise assembly of unsymmetrical supramolecular arrays containing porphyrins and coordination compounds

The stepwise coordination of meso-4'-pyridyl/phenyl porphyrins (4'-PyPs) to different metal centers proved to be an efficient synthetic approach leading to unsymmetrical arrays containing porphyrins and coordination compounds. The first step of this process, treatment of 4'-PyPs with a less than stoichiometric amount of cis,fac-RuCl2(Me2-SO)3(CO) (1), leads to the selective coordination of [cis,cis,cis-RuCl2(Me2SO)2(CO)] fragments ([Ru]) to some of the peripheral 4'-N sites of the 4'-PyPs. Column separation afforded four partially ruthenated 4'-PyPs in pure form: 4'-cis-DPyP[Ru] (2), 4'-trans-DPyP[Ru] (3), (4'-TPyP)[Ru] (4), and (4'-TPyP)[Ru]3 (5). These compounds, which have residual unbound peripheral 4'-N(py) sites (either one or three), were allowed to react with other metal centers that may belong either to a metalloporphyrin or to a coordination compound. When building blocks 2-5 were treated with [Ru(TPP)(CO)(EtOH)] (TPP = meso-tetraphenylporphyrin) in chloroform at room temperature, axial coordination of Ru(TPP)(CO) units ((Ru)) to the available 4'-N(py) sites readily occurred, generating the following arrays containing both perpendicular porphyrins and coordination compounds: (Ru)-(mu-4'-cis-DPyP)[Ru], (Ru)(mu-4'-trans-DPyP)[Ru], (Ru)3(mu-4'-TPyP)[Ru], and (Ru)(mu-4'-TPyP)[Ru]3. Furthermore, building blocks 2, 3, and 5 were treated with a series of coordination compounds capable of binding two pyridylporphyrins either cis to each other (trans-RuCl2(Me2SO)4 and trans,cis,cis-RuCl2(Me2SO)2(CO)2) or trans to each other (trans-PdCl2(C6H5CN)2). Homo- (Ru) and heterobimetallic (Ru-Pd) arrays with as many as seven metal atoms (six Ru and one Pd) and two 4'-PyPs were obtained as follows: trans,cis,cis-RuCl2(Me2SO)2(4'-cis-DPyP[Ru])2, trans,cis,cis-RuCl2(Me2SO)2(4'-trans-DPyP[Ru])2, trans,cis,cis-RuCl2(CO)2(4'-cis-DPyP[Ru])2, and trans-PdCl2(4'-TPyP[Ru]3)2. All the products were thoroughly characterized by 1H NMR spectroscopy. Since the [Ru] fragment is chiral, diastereomers are formed when two or more [Ru] units are bound to a porphyrin. We found that when two 4'-cis-DPyP[Ru] (2) units are coordinated cis to each other on the same metal center, the mutual anisotropic effect of the cis porphyrins differentiates the sulfoxide methyl resonances for the two forms. These and other results indicate that the pyridyl units react independently of the presence or absence of a substituent on the other py rings. Thus, the synthetic strategy should be a general method for linking diverse metal centers through pyridylporphyrins.     

Cisplatin--DNA cross-link models with an unusual type of chirality-neutral chelate amine carrier ligand, N,N dimethylpiperazine (Me2ppz): Me2ppzPt(guanosine monophosphate)2 adducts that exhibit novel properties

Most simple cis-PtA2G2 complexes that model the G-G cross-link DNA lesions caused by the clinically used anticancer drug cis-PtCl2(NH3)2 undergo large fluxional motions at a rapid rate (A2 = two amines or a diamine; G = guanine derivative). The carrier amine ligands in active compounds have NH groups, but the fundamental role of the NH groups has been obscured by the dynamic motion. To assess carrier ligand effects, we examine retro models, cis-PtA2G2 complexes, in which dynamic motion has been reduced by the incorporation of steric bulk into the carrier ligands. In this study we introduce a new approach employing the chirality-neutral chelate (CNC) ligand, Me2ppz (N,N'-dimethylpiperazine). Because they lie in the Pt coordination plane, the methyl groups of Me2ppz do not clash with the 06 of the base of G ligands in the ground state, but such clashes sterically hinder dynamic motion. NMR spectroscopy provided conclusive evidence that Me2ppzPt(GMP)2 complexes (GMP = 5'- and 3'-GMP) exist as a slowly interconverting mixture of two dominant head-to-tail (HT) conformers and a head-to-head (HH) conformer. Since the absence of carrier ligand chirality precluded using NMR methods to determine the absolute conformation of the two HT conformers, we used our recently developed CD pH jump method to establish chirality. The most abundant HT Me2ppzPt(5'-GMP)2 form had A chirality. Previously this chirality was shown to be favored by phosphate-cis G NIH hydrogen-bonding interligand interactions; such interactions also favor the HT conformers over the HH conformer. For typical carrier ligands, G O6 and phosphate interactions with the carrier ligand NH groups also favor the HT forms. These latter interactions are absent in Me2ppzPt(GMP)2 complexes, but the HT forms are still dominant. Nevertheless, we do find the first evidence for an HH form of a simple cis-PtA2G2 model with A2 lacking any NH groups. In previous studies, the absence of the HH conformer in cis-PtA2G2 complexes lacking carrier NH groups may be due to the presence of out-of-plane carrier ligand bulk. Such bulk forces both G O6-G O6 and G O6-carrier ligand clashes, thereby disfavoring the HH form. The major DNA cross-link adduct has the HH conformation. Thus, for anticancer activity, the small bulk of the NH group may be more important than the H-bonding interaction.     

NMR studies of models having the Pt(d(GpG)) 17-membered macrocyclic ring formed in DNA by platinum anticancer drugs: Pt complexes with bulky chiral diamine ligands

The highly distorted Pt(d(G*pG*)) (G* = N7-platinated G) 17-membered macrocyclic ring formed by cisplatin anticancer drug binding to DNA alters the structure of the G*G* base pair steps, canting one base, and increases dynamic motion, complicating solution structural studies. However, the ring appears to favor the HH1 conformation (HH1 denotes head-to-head guanine bases, 1 denotes the normal direction of backbone propagation). Compared to cisplatin, analogues with NH groups in the carrier ligand replaced by bulky N-alkyl groups are more toxic and less active and form less dynamic adducts. To examine the molecular origins for the biological effects of steric bulk, we evaluate Me(4)DABPt(d(G*pG*)) models; the bulk and chirality of Me(4)DAB (N,N,N',N'-tetramethyl-2,3-diaminobutane with S,S or R,R configurations at the chelate ring carbons) impede dynamic motion and enhance the utility of NMR methods for identifying and characterizing conformers. Unlike past studies of adducts with such bulky carrier ligands, in which no HH conformer was found, the Me(4)DABPt(d(G*pG*)) adducts did form the HH1 conformer, providing compelling evidence that the sugar-phosphate backbone can impose constraints sufficient to overcome the alkyl-group steric effects. The HH1 conformer exhibits no significant canting. The (S,S)-Me(4)DABPt(d(G*pG*)) adduct has the least amount of the "normal" HH1 conformer and the greatest amount of the ΔHT1 conformer (ΔHT1 = head-to-tail G* bases with Δ chirality) ever observed (88% under some conditions). Thus, our results lead us to hypothesize that the low activity and high toxicity of analogues of cisplatin having carrier ligands with N-alkyl groups arise from the low abundance and minimal canting of the HH1 conformer and possibly from the adverse effects of an abundant ΔHT1 conformer. The new findings advance our understanding of the chemistry of the Pt(d(G*pG*)) macrocyclic ring and of the effects of carrier-ligand steric bulk on the properties of the ring.     

Organolanthanide-catalyzed intramolecular hydroamination/cyclization of amines tethered to 1,2-disubstituted alkenes

[reaction: see text] This contribution reports the organolanthanide-catalyzed intramolecular hydroamination/cyclization of amines tethered to 1,2-disubstituted alkenes to afford the corresponding mono- and disubstituted pyrrolidines and piperidines by using coordinatively unsaturated complexes of the type (eta(5)-Me(5)C(5))(2)LnCH(TMS)(2) (Ln = La, Sm), [Me(2)Si(eta(5)-Me(4)C(5))(2)]NdCH(TMS)(2), [Et(2)Si(eta(5)-Me(4)C(5))(eta(5)-C(5)H(4))]NdCH(TMS)(2), and [Me(2)Si(eta(5)-Me(4)C(5))((t)()BuN)]LnE(TMS)(2) (Ln = Sm, Y, Yb, Lu; E = N, CH) as precatalysts. [Me(2)Si(eta(5)-Me(4)C(5))((t)BuN)]LnE(TMS)(2) mediates intramolecular hydroamination/cyclization of sterically demanding amino-olefins to afford disubstituted pyrrolidines in high diastereoselectivity (trans/cis = 16/1) and in good to excellent yield.     

Factors influencing conformer equilibria in retro models of cisplatin-DNA adducts as revealed by moderately dynamic (N,N'-dimethyl-2,3-diaminobutane)PtG(2) retro models (G = a guanine derivative)

Typical cis-PtA(2)G(2) models of key DNA lesions formed by cis-type Pt anticancer drugs are very dynamic and difficult to characterize (A(2) = diamine or two amines; G = guanine derivative). Retro models have A(2) carrier ligands designed to decrease dynamic motion without eliminating any of three possible conformers with bases oriented head-to-tail (two: DeltaHT and LambdaHT) or head-to-head (one: HH). All three were found in NMR studies of eight Me(2)DABPtG(2) retro models (Me(2)DAB = N,N'-dimethyl-2,3-diaminobutane with S,R,R,S and R,S,S,R configurations at the chelate ring N, C, C, and N atoms, respectively; G = 5'-GMP, 3'-GMP, 5'-IMP, and 3'-IMP). The bases cant to the left (L) in (S,R,R,S)-Me(2)DABPtG(2) adducts and to the right (R) in (R,S,S,R)-Me(2)DABPtG(2) adducts. Relative to the case in which the bases are both not canted, canting will move the six-membered rings closer in to each other ("6-in" form) or farther out from each other ("6-out" form). Interligand interactions between ligand components near to Pt (first-first sphere communication = FFC) or far from Pt (second-sphere communication = SSC) influence stability. In typical cases at pH < 8, the "6-in" form is favored, although the larger six-membered rings of the bases are close. In minor "6-out" HT forms, the proximity of the smaller five-membered rings could be sterically favorable. Also, G O6 is closer to the sterically less demanding NH part of the Me(2)DAB ligand, possibly allowing G O6-NH hydrogen bonding. These favorable FFC effects do not fully compensate for possibly stronger FFC dipole effects in the "6-in" form. SSC, phosphate-N1H cis G interactions favor LambdaHT forms in 5'-GMP and 5'-IMP complexes and DeltaHT forms in 3'-GMP and 3'-IMP complexes. When SSC and FFC favor the same HT conformer, it is present at >90% abundance. In six adducts [four (S,R,R,S)-Me(2)DABPtG(2) and (R,S,S,R)-Me(2)DABPtG(2) (G = 3'-GMP and 3'-IMP)], the minor "6-out" HT form at pH approximately 7 becomes the major form at pH approximately 10, where G N1H is deprotonated, because the large distance between the negatively charged N1 atoms minimizes electrostatic repulsion and probably because the G O6-(NH)Me(2)DAB H-bond (FFC) is strengthened by N1H deprotonation. At pH approximately 10, phosphate-negative N1 repulsion is an unfavorable SSC term. This factor disfavors the LambdaHT R form of two (R,S,S,R)-Me(2)DABPtG(2) (G = 5'-GMP and 5'-IMP) adducts to such an extent that the "6-in" DeltaHT R form remains the dominant form even at pH approximately 10.     

Cisplatin-DNA cross-link retro models with a chirality-neutral carrier ligand: evidence for the importance of "second-sphere communication"

We employ retro models, cis-PtA2G2 (A2 = a diamine, G = guanine derivative), to assess the cross-linked head-to-head (HH) form of the cisplatin-DNA d(GpG) adduct widely postulated to be responsible for the anticancer activity. Retro models are designed to have minimal dynamic motion to overcome problems recognized in models derived from cisplatin [A2 = (NH3)2]; the latter models are difficult to understand due to rapid rotation of G bases about the Pt-N7 bond in solution and the dominance of the head-to-tail (HT) form in the solid. Observation of an HH form is unusual for cis-PtA2G2 models. Recently, we found the first HH forms for a cis-PtA2G2 model with A2 lacking NH groups in a study of new Me2ppzPtG2 models. (Me2ppz, N,N'-dimethylpiperazine, has inplane bulk which reduces dynamic motion by clashing with the G O6 as the base rotates into the coordination plane from the ground state position approximately perpendicular to this plane G = 5'-GMP and 3'-GMP.) The finding of an HH form (albeit in a mixture with HT forms) with both G H8 signals unusually downfield encouraged us to study additional Me2ppzPtG2 analogues in order to explain the unusual spectral features and to identify factors that influence the relative stability of HT and HH forms. Molecular modeling techniques suggest HH structures with the H8's close to the deshielding region of the z axis of the magnetically anisotropic Pt atom, explaining the atypical shift pattern. When G = 1-Me-5'-GMP, we obtained NMR evidence that the HH rotamer has a high abundance (34%) and that the three rotamers have nearly equal abundance. These findings and the observation that the relative HT distributions varied little or not at all as a function of pH when G = Guo, 1-MeGuo, or 1-Me-5'-GMP are consistent with two of our earlier proposals concerning phosphate groups in HT forms of cis-PtA2(GMP)2 complexes. We proposed that a G phosphate group can form hydrogen bonds with the cis G N1H ("second-sphere" communication) and (for 5'-phosphate) A2 NH groups. The new results with 1-Me-5'-GMP led us to propose a new role for a 5'-phosphate group; it can also favor the HH form by counteracting the natural preference for the G bases to adopt an HT orientation. Finally, the HH form was also sufficiently abundant to allow observation of a distinct 195Pt NMR signal (downfield of the resonance observed for the HT forms) for several complexes. This is the first report of an HH 195Pt NMR signal for cis-PtA2G2 complexes.     

Restricted rotation in unbridged sandwich complexes: rotational behavior of closo-[Co(eta 5-NC4H4)(C2B9H11)] derivatives

Rotation about the centroid/metal/centroid axis in ferrocene is facile; the activation energy is 1-5 kcal mol(-1). The structurally similar sandwich complexes derived from closo-[3-Co(eta5-NC4H4)-1,2-C2B9H11] (1) have a different rotational habit. In 1, the cis rotamer in which the pyrrolyl nitrogen atom bisects the carboranyl cluster atoms is 3.5 kcal mol(-1) more stable in energy than the rotamer that is second lowest in energy. This cis rotamer is wide, spanning 216 degrees , and may be split into three rotamers of almost equal energy by substituting the N and the carboranyl carbon atoms adequately. To support this statement, closo-[3-Co(eta5-NC4H4)-1,2-(CH3)2-1,2-C2B9H9] (2), closo-[3-Co(eta5-NC4H4)-1,2-(mu-CH2)3-1,2-C2B9H9] 3, 2-->BF3, and 3-->BF3 have been prepared. Two rotamers are found at low temperature for 2-->BF(3) and 3-->BF3. Compounds 2, 3, and 1-->BF3 behave similarly to 1. Rotational energy barriers and the relative populations of the different energy states are calculated from 1H DNMR spectroscopy (DNMR, dynamic NMR). These results agree with those of semiempirical calculations. Without exception, the cis rotamer is energetically the more stable. The fixed conformation of 1 assists in elucidating the rotational preferences of the [3,3'-Co(1,2-C2B9H11)2]- ion in the absence of steric hindrance; the [3,3'-Co(1,2-C2B9H11)2]- ion is commonly accepted to present a cisoid orientation. Complex 1 is electronically similar to the [3,3'-Co(1,2-C2B9H11)2]- ion. Both have heteroatoms in the pi ligands, and they have the same electronegativity difference between the constituent atoms. This leads to a view of the [NC4H4]- as [7,8-C2B9H11]2- ion, with no steric implications. Therefore the [3,3'-Co(1,2-C2B9H11)2]- ion should be considered to have a cisoid structure, and the different rotamers observed to be the result of steric factors and of the interaction of the counterion with either B-H groups and/or ancillary ligands. The rotamer adopted is the one with the atoms holding the negative charges furthest apart.     

Ln4(CH2)4 cubane-type rare-earth methylidene complexes consisting of "(C5Me4SiMe3)LnCH2" units (Ln = Tm, Lu)

Tetranuclear cubane-type rare-earth methylidene complexes consisting of four "Cp'LnCH(2)" units, [Cp'Ln(μ(3)-CH(2))](4) (4-Ln; Ln = Tm, Lu; Cp' = C(5)Me(4)SiMe(3)), have been obtained for the first time through CH(4) elimination from the well-defined polymethyl complexes [Cp'Ln(μ(2)-CH(3))(2)](3) (2-Ln) or mixed methyl/methylidene precursors such as [Cp'(3)Ln(3)(μ(2)-Me)(3)(μ(3)-Me)(μ(3)-CH(2))] (3-Ln). The reaction of the methylidene complex 4-Lu with benzophenone leads to C═O bond cleavage and C═C bond formation to give the cubane-type oxo complex [Cp'Lu(μ(3)-O)](4) and CH(2)═CPh(2), while the methyl/methylidene complex 3-Tm undergoes sequential methylidene addition to the C═O group and ortho C-H activation of the two phenyl groups of benzophenone to afford the bis(benzo-1,2-diyl)ethoxy-chelated trinuclear complex [Cp'(3)Tm(3)(μ(2)-Me)(3){(C(6)H(4))(2)C(O)Me}] (6-Tm).