Chirality-controlling chelate (CCC) ligands are a class of chiral diamine ligands with one or two chiral secondary amine ligating groups. Analogues of platinum anticancer agents containing CCC ligands exhibit unusual steric and dynamic features. In this study NMR and CD methods were used to evaluate the influence of the N9 substituent in guanine derivatives (G) on conformer distribution in one class of (CCC)PtG(2)() complexes. We employed the CCC ligand, N,N'-dimethyl-2,3-diaminobutane [Me(2)()DAB with S,R,R,S or R,S,S,R configurations at the four asymmetric centers, N, C, C, and N]. For each Me(2)()DABPtG(2) complex, the presence of four G H8 signals demonstrated formation of all three possible atropisomers: DeltaHT (head-to-tail), LambdaHT, and HH (head-to-head). Different G ligands (5'-GMP, 3'-GMP, 1-MeGuo, Guo, or 9-EtG) were chosen to assess the effect of the N9 substituent on the relative stability and spectral properties of the atropisomers. The conformations of the atropisomers of Me(2)()DABPtG(2) were determined from CD spectra and from NOE cross-peaks (assigned via COSY spectra) between G H8 signals and those for the Me(2)()DAB protons. Regardless of the N9 substituent, the major form was HT. However, this form had the opposite chirality, LambdaHT and DeltaHT, and base tilt direction, left- and right-handed, respectively, for the S,R,R,S and R,S,S,R configurations of the Me(2)()DAB ligand. Thus, the chirality of the CCCligand, not hydrogen bonding, is the most important determinant of conformation. For each Me(2)()DABPtG(2) complex, the tilt direction of all three atropisomers is the same and, except for 5'-GMP, the order of abundance was major HT > minor HT > HH. For 5'-GMP, the HH atropisomer was three times as abundant as the minor HT species, suggesting that phosphate-NH(Me(2)()DAB) hydrogen bonds could be present since such bonding is possible only for the 5'-GMP derivatives. However, if such phosphate-NH hydrogen bonds exist, they are weak since the percentage of the major HT form of 5'-GMP complexes is similar and indeed can be smaller compared to this percentage for complexes with other G's. The CD spectra of all (S,R,R,S)-Me(2)()DABPtG(2) complexes were similar and opposite to those of all (R,S,S,R)-Me(2)()DABPtG(2) complexes, indicating the CD signature is characteristic of the dominant HT conformer, which has a chirality dictated by the chirality of the CCC ligand and not the N9 substituent.

We demonstrate that a tertiary sulfonamide group, N(SO2R)R′2, can re-hybridize to form a M–N bond of normal length even when the group is in a linear tridentate ligand, such as in the new tridentate N(SO2R)dpa ligands derived from di-(2-picolyl)amine (N(H)dpa). N(SO2R)dpa ligands were used to prepare fac-[Re(CO)3(N(SO2R)dpa)](PF6 or BF4) complexes. Structural characterization of the new complexes established that the tertiary sulfonamide nitrogen atom binds to Re with concomitant sp2-to-sp3 re-hybridization, facilitating facial coordination. The new fac-[Re(CO)3(N(SO2R)dpa)]X structures provide the only examples for any metal with the sulfonamide as part of a noncyclic linear tridentate ligand and with a normal metal-to-nitrogen(tertiary sulfonamide) bond length. Rare previous examples of such normal M–N bonds have been found only in more constrained situations, such as with tripodal tetradentate ligands. Our long-term objectives for the new tridentate N(SO2R)dpa ligands are to develop the fundamental chemistry relevant to the eventual use of the fac-[MI(CO)3]+ core (M = 99mTc, 186/188Re) in imaging and therapy. The sulfonamide group uniquely contributes to two of our goals: expanding ways to conjugate the fac-[MI(CO)3]+ core to biological molecules and also developing new symmetrical tridentate ligands that can coordinate facially to this core. Tests of our conjugation method, conducted by linking the fac-[ReI(CO)3]+ core to a new tetraarylporphyrin (T(N(SO2C6H4)dpa)P) as well as to a dansyl (5-(dimethylamino)naphthalene-1-sulfonyl) group, demonstrate that large molecular fragments can be tethered via a coordinated tertiary sulfonamide linkage to this core.

Early studies on cis-PtA2(d(G*pG*)) (A2 = diamine or two amines, G* = N7-platinated G) and cis-Pt(NH3)2(d(G*pG*)) models for the key cisplatin−DNA cross-link suggested that they exist exclusively or mainly as the HH1 conformer (HH1 = head-to-head G* bases, with 1 denoting the normal direction of backbone propagation). These dynamic models are difficult to characterize. Employing carrier A2 ligands designed to slow dynamic interchange of conformers, we found two new conformers, ΔHT (head-to-tail G* bases with a Δ chirality) and HH2 (with 2 denoting the backbone propagation direction opposite to normal). However, establishing that the non-HH1 conformations exist as an intrinsic feature of the 17-membered Pt(d(G*pG*)) ring requires exploring a range of different carrier ligands. Here we employ the planar aromatic sp2 N-donor 5,5‘-Me 2 bipy (5,5‘-dimethyl-2,2‘-bipyridine) ligand, having a shape very different from those of previously used nonplanar sp3 N-donor bidentate carrier ligands, which often bear NH groups. The 5,5‘-Me 2 bipy H6 and H6‘ protons project toward the d(G*pG*) moiety and hinder the dynamic motion of 5,5‘-Me 2 bipyPt(d(G*pG*)). We again found HH1, HH2, and ΔHT conformers with typical properties, supporting the conclusions that the new ΔHT and HH2 conformers exist universally in dynamic cis-PtA2(d(G*pG*)) adducts, including cis-Pt(NH3)2(d(G*pG*)), and that the carrier ligand typically has little influence on the overall structure of the Pt(d(G*pG*)) macrocyclic ring of a given conformer. The sizes of the G* H8 to H6/H6‘ NOE cross-peaks indicate little base canting in all 5,5‘-Me 2 bipyPt(d(G*pG*)) conformers, suggesting that carrier-ligand NH groups favor the canting of one G* base in the HH1 and HH2 conformers of typical cis-PtA2(d(G*pG*)) adducts.

Polyamine ligands (L) have excellent binding characteristics for the formation of fac-99mTc(CO)3-based radiopharmaceuticals. Normally, these L are elaborated so as to leave pendant groups designed to impart useful biodistribution characteristics to the fac-[99mTc(CO)3L] imaging agent. Our goal is to lay a foundation for understanding the features of the bound elaborated ligands by using the fac-[Re(CO)3L]-analogue approach with the minimal prototypical ligands, diethylenetriamine (dien) or simple dien-related derivatives. Treatment of the fac-[Re(CO)3(H2O)3]+ cation with such triamine (NNN) ligands afforded fac-[Re(CO)3L]+ complexes. Ligand variations included having a central amine thioether donor, thus allowing X-ray crystallographic and NMR spectroscopic comparisons of fac-[Re(CO)3L]+ complexes with NNN and NSN ligands. fac-[Re(CO)3L]+ complexes with two terminal exo-NH groups exhibit unusually far upfield exo-NH NMR signals in DMSO-d6. Upon the addition of Cl-, these exo-NH signals move downfield, while the signals of any endo-NH or central NH groups move very little. This behavior is attributed to the formation of 1:1 ion pairs having selective Cl- hydrogen bonding to both exo-NH groups. Base addition to a DMSO-d6 solution of meso-exo-[Re(CO)3(N,N',N''-Me3dien)]PF6 led to isomerization of only one NHMe group, producing the chiral isomer. The meso isomer did not form. The [Re(CO)3(N,N,N',N'',N''-pentamethyldiethylenetriamine)]triflate.[Re(CO)3(mu3-OH)]4.3.35H2O crystal, the first structure with a fac-[Re(CO)3L] complex cocrystallized with this well-known cluster, provided parameters for a bulky NNN ligand and also reveals CO-CO interlocking intermolecular interactions that could stabilize the crystal.