Octamethyl tetraazamacrocycle, Me8[14]diene·2HClO4 and its three isomeric ligands (LA, LB and LC) were synthesized and characterized using analytical and spectroscopic data, and the antibacterial activities were evaluated against selected bacteria and yeast. Interaction of LC with excess acrylonitrile resulted in an N-pendent derivative (LCX). Square planar nickel(II) diperchlorate complex of LC, [NiLCα](ClO4)2, underwent axial addition reactions with KI and NaNO2 to yield six coordinated octahedral species, [NiLCαI2]·2H2O and [NiLCα(NO2)(ClO4)]. Five coordinated square pyramidal Ni(II) complexes, [NiLCXCl](ClO4), [NiLCX(NCS)](NO3) and [NiLCXI](NO3), were synthesized from Ni(II) salts and tetraazamacrocyclic ligand LCX. Among the complexes, [NiLCXCl](ClO4) was synthesized through the direct interaction of NiCl2 with LCX, followed by the subsequent addition of NaClO4·6H2O. On the other hand, [NiLCX(NCS)](NO3) and [NiLCXI](NO3) as well as octahedral [NiLCXBr2] and [NiLCX(NO2)(NO3)] were synthesized by the interaction of LCX with different Ni(II) salts.

Purine nucleoside phosphorylase (PNP) is one of the major enzymes in the purine salvage pathway. It is responsible for the elevation of deoxyguanosine, and thus considered as the potent target in T-cell lymphoma. The present study examined acyclovir, reported as a low-affinity PNP inhibitor, for the rational design of new acyclovir derivatives by incorporating halogens, hydroxyl, and bulky amino groups. The molecular actions of designed derivatives were investigated by employing density functional theory, molecular docking, and binding energy calculations. The results revealed that the newly designed compounds were highly stable and showed more affinity to PNP than the parent compound, acyclovir. The quantum mechanics and molecular docking studies suggested that modification of side chains with bulky polar groups provided better binding affinities than substitutions with halogens. The resultant derivatives have strong polar interactions like His257 and Tyr88. Furthermore, the designed derivatives were within the ideal range of ADMET (absorption, distribution, metabolism, elimination, and toxicity) analysis. Considering that, these findings recommend further validation of designed acyclovir derivatives in wet lab confirmatory analysis with the emphasis on the further improvements in the treatment of T-cell-mediated diseases.