ABSTRACT
This is a case of a woman in her 50s with HIV and uncontrolled diabetes who presented to the emergency department with urinary retention and a painful gluteal cleft lesion, admitted for cellulitis. Since initial CT and soft tissue ultrasound (US) were negative for fluid collection, the care team was surprised to find her symptoms continued to progress despite intravenous antibiotics. Finally, MRI 9 days into her admission demonstrated a 12-cm perirectal horseshoe abscess. The patient was ultimately treated with incision and drainage with Penrose drain placement. This case demonstrates the importance of maintaining a high suspicion for horseshoe abscess, a complex form of ischiorectal fossa abscess which can be missed on CT and US imaging, and which may expand rapidly in immunosuppressed patients.
Subject(s)
Abscess , Delayed Diagnosis , Drainage , Humans , Female , Middle Aged , Abscess/diagnostic imaging , Abscess/diagnosis , Drainage/methods , Magnetic Resonance Imaging , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Rectal Diseases/diagnosis , Rectal Diseases/diagnostic imaging , Tomography, X-Ray Computed , HIV Infections/complications , Buttocks/diagnostic imaging , Urinary Retention/etiologyABSTRACT
Growth of the library of tetraaza macrocyclic pyridinophane ligands is a result of the potential to treat neurodegenerative diseases by binding unregulated redox active metal-ions, scavenging radicals, and reducing oxidative stress. As part of this work, the copper complex of OH PyN 3 Cu (3,6,9,15-tetraazabicyclo[9.3.1]penta-deca-1(15),11,13-trien-13-ol) was previously identified as a discrete molecule in the solid state when isolated at lower pH values. However, here we report that OH PyN 3 Cu forms a helical structure upon crystallization around pH 6.5. Several properties of the ligand and complex were evaluated to understand the driving forces that led to the concatenation and formation of this solid-state helix. DFT studies along with a comparison of keto/enol tautomerization stability and bond lengths were used to determine the keto-character of the C=O within each subunit. This pH dependent keto-enol tautomerization is responsible for the solid state intermolecular C=O···Cu bonds observed in this metallohelix (Cu1 H ) when produced around pH 6.5. Perchlorate templating that occurs through hydrogen bonding between perchlorate counter ions and each Cu1 H unit is the primary driving factor for the twist that leads to the helix structure. Cu1 H does not exhibit the typical factors that stabilize the formation of helices, such as intra-strand hydrogen bonding or π-stacking. The helix structure further highlights the diversity of inorganic metallohelices and demonstrates the importance of tautomerization and pH that occurs with the pyridinophane ligand used in this study. To our knowledge and although these phenomenon have been observed individually, this is the first example of a pH dependent keto-enol tautomerization in an azamacrocycle being the driving force for the formation of a metallohelix solid state structure and is a particularly unique observation for pyridinophane complexes.
ABSTRACT
Alzheimer's and other neurodegenerative diseases are chronic conditions affecting millions of individuals worldwide. Oxidative stress is a consistent component described in the development of many neurodegenerative diseases. Therefore, innovative strategies to develop drug candidates that overcome oxidative stress in the brain are needed. To target these challenges, a new, water-soluble 12-membered tetraaza macrocyclic pyridinophane L4 was designed and produced using a building-block approach. Potentiometric data show that the neutral species of L4 provides interesting zwitterionic behavior at physiological pH, akin to amino acids, and a nearly ideal isoelectric point of 7.3. The copper(II) complex of L4 was evaluated by X-ray diffraction and cyclic voltammetry to show the potential modes of antioxidant activity derived, which was also demonstrated by 2,2-diphenyl-1-picrylhydrazyl and coumarin carboxylic acid antioxidant assays. L4 was shown to have dramatically enhanced antioxidant activity and increased biological compatibility compared to parent molecules reported previously. L4 attenuated hydrogen peroxide (H2O2)-induced cell viability loss more efficiently than precursor molecules in the mouse hippocampal HT-22 cell model. L4 also showed potent (fM) level protection against H2O2 cell death in a BV2 microglial cell culture. Western blot studies indicated that L4 enhanced the cellular antioxidant defense capacity via Nrf2 signaling activation as well. Moreover, a low-cost analysis and high metabolic stability in phase I and II models were observed. These encouraging results show how the rational design of lead compounds is a suitable strategy for the development of treatments for neurodegenerative diseases where oxidative stress plays a substantial role.