Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Five-Coordinate [Pt^II(bipyridine)₂(phosphine)]^<i>n</i>+ Complexes: Long-Lived Intermediates in Ligand Substitution Reactions of [Pt(bipyridine)₂]²⁺ with Phosphine Ligands

The reaction of [Pt­(N–N)₂]²⁺ [N–N = 2,2′-bipyridine (bpy) or 4,4′-dimethyl-2,2′-bipyridine (4,4′-Me₂bpy)] with phosphine ligands [PPh₃ or PPh­(PhSO₃)₂^2–] in aqueous or methanolic solutions was studied by multinuclear (¹H, ¹³C, ³¹P, and ¹⁹⁵Pt) NMR spectroscopy, X-ray crystallography, UV–visible spectroscopy, and high-resolution mass spectrometry. NMR spectra of solutions containing equimolar amounts of [Pt­(N–N)₂]²⁺ and phosphine ligand give evidence for rapid formation of long-lived, 5-coordinate [Pt^II(N–N)₂(phosphine)]^<i>n</i>+ complexes. In the presence of excess phosphine ligand, these intermediates undergo much slower entry of a second phosphine ligand and loss of a bpy ligand to give [Pt^II(N–N)­(phosphine)₂]^<i>n</i>+ as the final product. The coordination of a phosphine ligand to the Pt­(II) ion in the intermediate [Pt­(N–N)₂(phosphine)]^<i>n</i>+ complexes is supported by the observation of ³¹P–¹⁹⁵Pt coupling in the ³¹P NMR spectra. The 5-coordinate nature of [Pt­(bpy)₂­{PPh­(PhSO₃)₂}] is confirmed by X-ray crystallography. X-ray crystal structural analysis shows that the Pt­(II) ion in [Pt­(bpy)₂{PPh­(PhSO₃)₂}]·5.5H₂O displays a distorted square pyramidal geometry, with one bpy ligand bound asymmetrically. These results provide strong support for the widely accepted associative ligand substitution mechanism for square planar Pt­(II) complexes. X-ray structural characterization of the distorted square planar complex [Pt­(bpy)­(PPh₃)₂]­(ClO₄)₂ confirms this as the final product of the reaction of [Pt­(bpy)₂]²⁺ with PPh₃ in CD₃OD. The results of density functional calculations on [Pt­(bpy)₂]²⁺, [Pt­(bpy)₂­(phosphine)]^<i>n</i>+, and [Pt­(bpy)­(phosphine)₂]^<i>n</i>+ indicate that the bonding energy follows the trend of [Pt­(bpy)­(phosphine)₂]^<i>n</i>+ > [Pt­(bpy)₂­(phosphine)]^<i>n</i>+ > [Pt­(bpy)₂]²⁺ for stability and that the formation reactions of [Pt­(bpy)₂­(phosphine)]^<i>n</i>+ from [Pt­(bpy)₂]²⁺ and [Pt­(bpy)­(phosphine)₂]^<i>n</i>+ from [Pt­(bpy)₂­(phosphine)]^<i>n</i>+ are energetically favorable. These calculations suggest that the driving force for the formation of [Pt­(bpy)­(phosphine)₂]^<i>n</i>+ from [Pt­(bpy)₂]²⁺ is the formation of a more energetically favorable product

A Dinuclear Platinum(II) N4Py Complex: An Unexpected Coordination Mode For N4Py

The polypyridyl compound <i>N</i>,<i>N</i>-bis­(2-pyridylmethyl)-<i>N</i>-bis­(2-pyridyl)­methylamine (N4Py) acts as a bridging ligand and coordinates to two Pt­(II) ions giving an unexpected diplatinum­(II) complex, whose photophysical and anticancer properties were investigated

Comparison of Inverse and Regular 2‑Pyridyl-1,2,3-triazole “Click” Complexes: Structures, Stability, Electrochemical, and Photophysical Properties

Two inverse 2-pyridyl-1,2,3-triazole “click” ligands, 2-(4-phenyl-1<i>H</i>-1,2,3-triazol-1-yl)­pyridine and 2-(4-benzyl-1<i>H</i>-1,2,3-triazol-1-yl)­pyridine, and their palladium­(II), platinum­(II), rhenium­(I), and ruthenium­(II) complexes have been synthesized in good to excellent yields. The properties of these inverse “click” complexes have been compared to the isomeric regular compounds using a variety of techniques. X-ray crystallographic analysis shows that the regular and inverse complexes are structurally very similar. However, the chemical and physical properties of the isomers are quite different. Ligand exchange studies and density functional theory (DFT) calculations indicate that metal complexes of the regular 2-(1-<b>R</b>-1<i>H</i>-1,2,3-triazol-4-yl)­pyridine (<b>R</b> = phenyl, benzyl) ligands are more stable than those formed with the inverse 2-(4-<b>R</b>-1<i>H</i>-1,2,3-triazol-1-yl)­pyridine (<b>R</b> = phenyl, benzyl) “click” chelators. Additionally, the <i>bis</i>-2,2′-bipyridine (bpy) ruthenium­(II) complexes of the “click” chelators have been shown to have short excited state lifetimes, which in the inverse triazole case, resulted in ejection of the 2-pyridyl-1,2,3-triazole ligand from the complex. Under identical conditions, the isomeric regular 2-pyridyl-1,2,3-triazole ruthenium­(II) bpy complexes are photochemically inert. The absorption spectra of the inverse rhenium­(I) and platinum­(II) complexes are red-shifted compared to the regular compounds. It is shown that conjugation between the substituent group <b>R</b> and triazolyl unit has a negligible effect on the photophysical properties of the complexes. The inverse rhenium­(I) complexes have large Stokes shifts, long metal-to-ligand charge transfer (MLCT) excited state lifetimes, and respectable quantum yields which are relatively solvent insensitive

Excited States of Triphenylamine-Substituted 2‑Pyridyl-1,2,3-triazole Complexes

A new 2-pyridyl-1,2,3-triazole (pytri) ligand, TPA-pytri, substituted with a triphenylamine (TPA) donor group on the 5 position of the pyridyl unit was synthesized and characterized. Dichloroplatinum­(II), bis­(phenylacetylide)­platinum­(II), bromotricarbonylrhenium­(I), and bis­(bipyridyl)­ruthenium­(II) complexes of this ligand were synthesized and compared to complexes of pytri ligands without the TPA substituent. The complexes of unsubstituted pytri ligands show metal-to-ligand charge-transfer (MLCT) absorption bands involving the pytri ligand in the near-UV region. These transitions are complemented by intraligand charge-transfer (ILCT) bands in the TPA-pytri complexes, resulting in greatly improved visible absorption (λ_max = 421 nm and ϵ = 19800 M^–1 cm^–1 for [Pt­(TPA-pytri)­Cl₂]). The resonance Raman enhancement patterns allow for assignment of these absorption bands. The [Re­(TPA-pytri)­(CO)₃Br] and [Pt­(TPA-pytri)­(CCPh)₂] complexes were examined with time-resolved infrared spectroscopy. Shifts in the CC and CO stretching bands revealed that the complexes form states with increased electron density about their metal centers. [Pt­(TPA-pytri)­Cl₂] is unusual in that it is emissive despite the presence of deactivating d–d states, which prevents emission from the unsubstituted pytri complex

Excited States of Triphenylamine-Substituted 2‑Pyridyl-1,2,3-triazole Complexes

A new 2-pyridyl-1,2,3-triazole (pytri) ligand, TPA-pytri, substituted with a triphenylamine (TPA) donor group on the 5 position of the pyridyl unit was synthesized and characterized. Dichloroplatinum­(II), bis­(phenylacetylide)­platinum­(II), bromotricarbonylrhenium­(I), and bis­(bipyridyl)­ruthenium­(II) complexes of this ligand were synthesized and compared to complexes of pytri ligands without the TPA substituent. The complexes of unsubstituted pytri ligands show metal-to-ligand charge-transfer (MLCT) absorption bands involving the pytri ligand in the near-UV region. These transitions are complemented by intraligand charge-transfer (ILCT) bands in the TPA-pytri complexes, resulting in greatly improved visible absorption (λ_max = 421 nm and ϵ = 19800 M^–1 cm^–1 for [Pt­(TPA-pytri)­Cl₂]). The resonance Raman enhancement patterns allow for assignment of these absorption bands. The [Re­(TPA-pytri)­(CO)₃Br] and [Pt­(TPA-pytri)­(CCPh)₂] complexes were examined with time-resolved infrared spectroscopy. Shifts in the CC and CO stretching bands revealed that the complexes form states with increased electron density about their metal centers. [Pt­(TPA-pytri)­Cl₂] is unusual in that it is emissive despite the presence of deactivating d–d states, which prevents emission from the unsubstituted pytri complex