Multilevel Fragmentation and Boundary Corrections for Accurate Vibrational Spectra of Large Molecules

Accurate anharmonic vibrational spectroscopy of medium-size molecules requires potential energy surfaces of near-spectroscopic quality, but the cost of direct high-level treatments rapidly becomes prohibitive when cubic and quartic force constants are needed. This limitation is especially severe for systems in the 30-50 atom range, where second-order vibrational perturbation theory (VPT2) remains one of the most attractive routes to quantitative vibrational analyses. Conventional dual-level schemes provide an effective compromise by combining high-level harmonic force fields with lower level anharmonic corrections for the full molecule. We introduce a multilevel fragmentation strategy based on the chemically meaningful subunits. When a single high-level fragment dominates the spectroscopic problem, the corresponding correction can be propagated directly through an anharmonic treatment. When two complementary fragments contribute equally, the harmonic correction can instead be assembled at the frequency level through a mode-resolved combination of the multilevel results. In both cases, the approach avoids the projection and Hessian reconstruction steps that often complicate fragment-based anharmonic treatments. The approach is further extended by a local harmonic correction designed for electronically delicate boundary bonds, where the standard link atom approximation may leave a residual error concentrated in the harmonic force field. The correction is formulated in internal coordinates and can be transferred from the compact auxiliary models to the target system. Thus, the purely harmonic approximation is confined mainly to the fragment boundaries rather than to the entire molecule. The benzonitrile application shows that treating the nitrile group at the high level while retaining the aromatic ring at the low level already yields an accurate global description, and that a propionitrile-based local correction further improves the C≡N stretching region. More challenging test cases are provided by tryptophan and uridine, which probe, respectively, chromophore-centered and genuinely dual-fragment multilevel corrections in larger vibrational manifolds. Overall, the resulting strategy offers a practical route to VPT2-quality vibrational analyses for molecules that admit natural partitions into chemically meaningful subunits. In this framework, mode localization should be viewed as a criterion for defining chemically meaningful fragmentations, rather than as an intrinsic limitation of the method.