Carboxyl-coated nanotubes grip tuberculosis drug isoniazid, study shows
Researchers using DFT have found that carboxyl-functionalized single-walled carbon nanotubes bind the tuberculosis drug isoniazid with significantly increased strength.
A recent computational study highlights the potential of carboxyl-functionalized single-walled carbon nanotubes (SWCNTs) in enhancing the delivery of the tuberculosis drug isoniazid. Published in Results in Chemistry, the research demonstrates that isoniazid binds significantly stronger to these modified nanotubes compared to unmodified ones. The study, conducted by Shahla Hamedani, Melina Shadi, and Mohadese Moradi, delves into the electron density, orbital interactions, and nuclear magnetic resonance signatures of the drug–carrier bond.
The researchers constructed a finite, hydrogen-terminated fragment of an armchair (5,5) SWCNT, approximately 7 angstroms in length, with a diameter of about 6.8 angstroms. They decorated one end with a carboxyl group and used density functional theory to optimize the nanotube, the free isoniazid molecule, and various adsorption complexes. By analyzing the molecular electrostatic potential of isoniazid, the team identified the most energetically favorable configuration.
The study found that the lowest-energy configuration of isoniazid on the carboxyl-functionalized nanotube had an adsorption energy of −18.65 kcal per mole, significantly stronger than the approximately 2 kcal per mole for pristine nanotubes. This interaction remains within the noncovalent adsorption range, ideal for drug delivery as it balances strong binding with the ability to release the drug inside a cell. Even when modeled in a water-like environment, the adsorption energy remained favorable at −13.38 kcal per mole.
Thermodynamic analysis further supported these findings. At standard conditions, the adsorption enthalpy was −16.65 kcal per mole in the gas phase and −12.67 kcal per mole in water, with negative Gibbs free energy changes confirming the spontaneity of the process. The entropy change was negative, indicating a loss of freedom when the drug binds to the nanotube, with minimal impact from solvation.
The Quantum Theory of Atoms in Molecules revealed two specific hydrogen bonds between the nanotube and isoniazid, characterized by positive electron density Laplacians and negative local energy densities. Natural Bond Orbital analysis quantified the electronic interactions, showing significant electron density transfer from the nanotube’s carboxyl oxygen to the drug’s N–H bond.
Frontier molecular orbital analysis showed a reduction in the HOMO–LUMO gap from 4.76 to 1.74 electron volts upon complex formation, indicating increased electronic delocalization. The global hardness and electrophilicity changes suggest enhanced electronic stability of the complex. Spectroscopic analysis confirmed these findings, with notable shifts in NMR shielding and infrared spectra consistent with hydrogen bonding.
The authors acknowledge the model's limitations, including the use of a short nanotube fragment and the lack of experimental validation. However, the study suggests that carboxyl-functionalized SWCNTs could serve as effective carriers for isoniazid, potentially addressing drug resistance issues in tuberculosis treatment.
Source: Carbon Nanotubes Feed