Abstract
Spectinomycin, a tricyclic aminoglycoside antibiotic with peculiar chemical structure and pharmacological profile was characterized in terms of microscopic protonation constants. 1H-15N HMBC–pH titrations were carried out to allocate the order of basicities of the two similar methylamino functions of spectinomycin, and 1H NMR–pH titrations were performed on spectinomycin and actinamine, its symmetrical model compound to determine the basicity of the amino sites. It was found that the methylamino moiety in position 3 is of some 60% higher basicity than its counterpart in position 1, and protonation at one site decreases the basicity of the other site by 1.17 logk units. Both secondary amino sites as such are of relatively low basicity, due to the adjacent, electron-withdrawing 7 oxygens. At the pH of blood nearly equal amounts of di- and monocationic species coexist, while less than 1% of neutral spectinomycin occurs at this pH. The pHdependent distribution of the microspecies is depicted.
Keywords: Spectinomycin, microspeciation, 1H and 15N NMR-pH titration, site-specific basicities, pH-dependent species distribution.
Current Pharmaceutical Analysis
Title:The Site-specific Protonation Constants of Spectinomycin, Characterized by 1H and 15N NMR Methods
Volume: 11 Issue: 1
Author(s): Mate Somlyay, Gabor Orgovan and Bela Noszal
Affiliation:
Keywords: Spectinomycin, microspeciation, 1H and 15N NMR-pH titration, site-specific basicities, pH-dependent species distribution.
Abstract: Spectinomycin, a tricyclic aminoglycoside antibiotic with peculiar chemical structure and pharmacological profile was characterized in terms of microscopic protonation constants. 1H-15N HMBC–pH titrations were carried out to allocate the order of basicities of the two similar methylamino functions of spectinomycin, and 1H NMR–pH titrations were performed on spectinomycin and actinamine, its symmetrical model compound to determine the basicity of the amino sites. It was found that the methylamino moiety in position 3 is of some 60% higher basicity than its counterpart in position 1, and protonation at one site decreases the basicity of the other site by 1.17 logk units. Both secondary amino sites as such are of relatively low basicity, due to the adjacent, electron-withdrawing 7 oxygens. At the pH of blood nearly equal amounts of di- and monocationic species coexist, while less than 1% of neutral spectinomycin occurs at this pH. The pHdependent distribution of the microspecies is depicted.
Export Options
About this article
Cite this article as:
Somlyay Mate, Orgovan Gabor and Noszal Bela, The Site-specific Protonation Constants of Spectinomycin, Characterized by 1H and 15N NMR Methods, Current Pharmaceutical Analysis 2015; 11 (1) . https://dx.doi.org/10.2174/1573412910666140917213713
DOI https://dx.doi.org/10.2174/1573412910666140917213713 |
Print ISSN 1573-4129 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-676X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Enoyl Reductases as Targets for the Development of Anti-Tubercular and Anti-Malarial Agents
Current Drug Targets An Update on Natural Products with Carbonic Anhydrase Inhibitory Activity
Current Pharmaceutical Design Novel Drugs Targeting the c-Ring of the F<sub>1</sub>F<sub>O</sub>-ATP Synthase
Mini-Reviews in Medicinal Chemistry Quinoline Derivatives: Candidate Drugs for a Class B G-Protein Coupled Receptor, the Calcitonin Gene-Related Peptide Receptor, a Cause of Migraines
CNS & Neurological Disorders - Drug Targets Human Tuberculosis I. Epidemiology, Diagnosis and Pathogenetic Mechanisms
Current Medicinal Chemistry In-vitro Antioxidant activity of ‘Aswathy Chooranam’- a Siddha Drug
Current Traditional Medicine Predicting Antimicrobial Drugs and Targets with the MARCH-INSIDE Approach
Current Topics in Medicinal Chemistry In Silico (3D-QSAR) Designed, Study, Synthesis and Anti-tubercular Evaluation of Pyrazolo-Pyrimidine Derivatives
Anti-Infective Agents Synthesis, Characterization, Biological Activity and Voltammetric Behavior and Determination of Cefaclor Metal Complexes
Current Analytical Chemistry Graphical Abstracts
Letters in Drug Design & Discovery Is Renalase a Novel Player in Catecholaminergic Signaling? The Mystery of the Catalytic Activity of an Intriguing New Flavoenzyme
Current Pharmaceutical Design Adhatoda vasica Nees: Phytochemical and Pharmacological Profile
The Natural Products Journal Antimicrobial Peptides and their Pore/Ion Channel Properties in Neutralization of Pathogenic Microbes
Current Topics in Medicinal Chemistry Exploring the Potential Inhibition of Candidate Drug Molecules for Clinical Investigation Based on their Docking or Crystallographic Analyses against <i>M. tuberculosis</i> Enzyme Targets
Current Topics in Medicinal Chemistry Role of Type I Cytokines in Host Defense Against Mycobacterium avium Infection
Current Pharmaceutical Design Recent Patents on Novel P2X7 Receptor Antagonists and their Potential for Reducing Central Nervous System Inflammation
Recent Patents on CNS Drug Discovery (Discontinued) The Human Trypanolytic Factor: A Drug Shaped Naturally
Infectious Disorders - Drug Targets Editorial (Asia-Pacific Health 2020 and Genomics without Borders: Co-Production of Knowledge by Science and Society Partnership for Global Personalized Medicine)
Current Pharmacogenomics and Personalized Medicine New Analogues of Mycophenolic Acid
Mini-Reviews in Medicinal Chemistry The Physiology of Nitric Oxide: Control and Consequences
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents