Functional B3LYP Research Articles

Synthesis, Characterization, Theoretical Studies and in Vitro Embriyotoxic, Genotoxic and Anticancer Effects of Novel Phenyl(1,4,6-Triphenyl-2-Thioxo-1,2,3,4-Tetrahydropyrimidin-5-yl)Methanone

In this study, phenyl (1,4,6-triphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methanone was obtained by using the Biginelli reaction method. The structure of this compound was analyzed using elemental analysis, IR, 1H, and 13C NMR. The quantum chemical calculations (QCC) of this compound were performed density functional theory (DFT) method, 6–31 G (d, p) base set, and B3LYP functions with the Gaussian09W software package. Literature shows that pyrimidine-derived compounds have very active biological properties. For this reason, the biologically active properties of the synthesized compound were also examined. To determine embryotoxic, genotoxic, and cytotoxic effects of compound, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, micronucleus (MN) and 8-OH-dG assays were carried out. On the other hand, pharmacokinetic and toxicity properties (ADMET) were predicted in silico via SwissADME and Protox-II web tools. In silico estimates of this compound used in the study showed that the compound has the covetable physicochemical properties for bioavailability. In conclusion, the obtained results of our study clearly showed that this compound exerted strong toxicity potential.

Synthesis, SC-XRD structure, spectroscopy, intermolecular interactions, DFT/TD-DFT investigation, and (static, dynamic) NLO properties of (2E,5Z)-3-(4-fluorophenyl)-2-(4-fluorophenylimino)-5-((E)-3-(2-nitrophenyl) allyliden) thiazolidin-4-one

This paper describes the synthesis of a novel fluorine-substituted thiazolidin-4-one compound, (2E,5Z) -3-(4-fluorophenyl) -2-(4-fluorophenylimino) -5-((E)-3-(2-nitrophenyl) allyliden) thiazolidin-4-one, abbreviated as F2NTh. Its structure was subsequently characterized by Fourier transform infrared (FTIR), 1H and 13C nuclear magnetic resonance (NMR), UV–Visible, and single crystal X-ray diffraction (SC-XRD). For a better comprehension of the electronic structure of F2NTh, experimental data collected from the X-ray diffraction pattern were then compared to theoretical results computed by the density functional theory (DFT) using both B3LYP and CAM-B3LYP functionals with a 6–311 G (d, p) basis set. Theoretical results exhibited a good correlation with those established through the experimental analysis. To identify intra- and intermolecular interactions, Hirshfeld surface (HS) and reduced density gradient (RDG) analyses were performed. The results, including 2D fingerprint plots, indicated that H…H interactions played a major role, accounting for 23.6 % of the overall intermolecular contacts. To investigate the charge transfer and ascertain the electronic properties of F2NTh, frontier molecular orbitals and global and local chemical reactivity descriptors were studied. By simulating the molecular electrostatic potential (MEP) and using MPA, NPA, ESP, and MC5 atomic charges, reactive sites within the molecule responsible for electrophilic and nucleophilic attacks were identified. Some thermodynamic parameters and functions (enthalpy, heat capacity, and entropy) obtained from spectroscopic data were also examined in the temperature range of 100−1000 K. Finally, to test the title molecule in the non-linear optical (NLO) domain, the corresponding properties were predicted using B3LYP and CAM-B3LYP functionals. The predicted static NLO parameters (μ = 4.93 D, α = 56.23×10−24 esu, β = 28×10−30 esu, and γ = 244.98 × 10−36 esu) revealed highly promising outcomes, exhibiting the molecule's utility in NLO applications. This activity was confirmed by the dynamic NLO parameters showing a high third-order response.

Influence of Dispersion Interactions in the Diels-Alder Reaction of Cyclopentadiene, Anthracene and Tetracene with C60: A DFT Examination

Asbtract: The activation and thermodynamic parameters of the Diels-Alder reaction of cyclopentadiene, anthracene and tetracene with C60 fullerene are estimated at the DFT level using PBE0, B3LYP and CAM-B3LYP functionals and the effect of accounting for dispersion interactions in various semi-empirical Grimme models on these parameters. Structural characteristics of the reagents, products, pre-reaction van der Waals complex, and transition state are obtained. Taking into account dispersion corrections have practically no effect on the geometric characteristics of structures with the covalent type of the bond, as well as on the structure of the transition state. Still, it has a noticeable effect only on the structure of the pre-reaction complex, in which the interparticle interaction has a van der Waals character. At the same time, taking into account dispersion corrections plays a significant role in assessing the thermodynamic and activation parameters of the reaction. An analysis of the performed calculations showed that the combination of PBE0/def2-TZVP with the D4 model for dispersion interactions could be recommended for the Diels-Alder reaction considered above.

Theoretical Investigation of Anhydrofusarubin: Structural and Optical Properties

Anhydrofusarubin is a naphthoquinone pigment synthesized by a number of Fusarium genus fungi. Being a biologically active substance, it demonstrates promising antibiotic properties and rather good hypothetical effectiveness against certain types of cancer. In this regard, an important task arises to study the structural properties and spectral manifestation of Anhydrofusarubin in order to identify and characterize this substance in terms of synthesis and application purposes. In this regard, the aim of the article was to study the structure of the Anhydrofusarubin molecule and its structure-property correlation. The density functional theory was used to investigate the optical properties and stability of the molecular structures. The computational results obtained with B3LYP and wb97XD exchange correlation functionals and the triple zeta basis sets were compared with available experimental data. In addition to the ground state structure, a tautomer with slightly higher energy (by 0.78–0.9 kcal/mol) and a relatively small potential barrier was found. Also, the investigation of flexibility of the pyran ring reveals the presence of two conformational enantiomer forms, being in good agreement with the recent experimental data on the crystal structure. The vibrational and UV-visible absorption spectra were simulated and interpreted.

DFT Investigation of the Structural, Electronic, and Optical Properties of AsTi (Bi)-Phase ZnO under Pressure for Optoelectronic Applications

Pressure-induced phases of ZnO have attracted considerable attention owing to their excellent electronic and optical properties. This study provides a vital insight into the electronic structure, optical characteristics, and structural properties of the AsTi (Bi) phase of ZnO under high pressure via the DFT-based first-principles approach. The phase transformation from BN(Bk) to the Bi phase of ZnO is estimated at 16.1 GPa using local density approximation, whereas the properties are explored precisely by the hybrid functional B3LYP. The electronic structure exploration confirms that the Bi phase is an insulator with a wider direct bandgap, which expands by increasing pressure. The dielectric function evidenced that the Bi phase behaves as a dielectric in the visible region and a metallic material at 18 eV. Optical features such as the refractive index and loss function revealed the transparent nature of the Bi phase in the UV range. Moreover, the considered Bi phase is found to possess a high absorption coefficient in the ultraviolet region. This research provides strong theoretical support for the development of Bi-phase ZnO-based optoelectronic and photovoltaic devices.

Combined computational and experimental study: Synthesis, DFT-calculated and experimental characterization and application of new s-triazine based fiber reactive UV absorbers

The increased awareness of people about deleterious effects of UV radiations to human health was the motivation to develop the UV protective textiles. This research was focused to computationally design and synthesize fiber reactive UV absorbers using cyanuric chloride as starting synthetic building block having s-triazine scaffold. The computational profile of design compounds included optimized geometries, photophysical properties, FT-IR and Raman vibrational frequencies which were investigated at DFT level using CAMB3LYP and B3LYP functionals with 631-G (d, p) basis set. The designed target compounds successfully synthesized and chemical structures were characterized by ESI-MS, UV–Vis, ATR-FTIR, and Raman spectroscopy. The results of computational and experimental spectroscopic techniques are presented in comparison that showed excellent correlation. The synthesized UV absorbers were applied onto cotton fabric through simple pad-dry-cure technique and their potential as textile UV protective agent was evaluated by measuring UPF and wash durability. The finished fabric with synthesized compounds offered UPF value of 170 and 129 for UVA1 and UVA2 respectively and was persistent with UPF values of 134 and 118 even after 25 home launderings. The finished cotton fabrics were characterized by ATR-FTIR after 25 home launderings to identify the presence of different functional groups. The cotton fabric finished with synthesized compounds proved its potential as highly UV protective with long wash durable textile.

Enhancing the performance of quantum dot solar cells through halogen adatoms on carboxyl edge-functionalized graphene quantum dots

This research has been conducted to find new, high-performing, safe, and suitable materials for use in quantum dot solar cells (QDSCs). Specifically, impact of halogen adatoms (Br, Cl, and F) on carboxyl edge-functionalized graphene quantum dot (CO2H-GQD) has been investigated employing DFT-based first-principles computations. We analyzed energy gaps (Eg), LUMO, and HOMO to determine how the foreign atom affects electronic features of material, employing hybrid functional B3LYP with a 6-31G basis set. In order to investigate charge separation and electron injection in both doped and undoped CO2H-GQD, we examined charge transfer (CT), molecular electrostatic potential (MESP), and binding mechanism. Optical attributes also indicate a wide spectrum in visible range, making it suitable for harvesting solar light. Furthermore, we evaluated solar cell parameters, including efficiency (η), short circuit current density (Jsc), fill factor (FF), and open circuit voltage (Voc) to assess potential usage of adatom-doped CO2H-GQD in quantum dot solar cell. Subsequent to Br, Cl, and F substitutional doping, value of η for CO2H-GQD increased. In case of F doping, we achieved maximum η, which has electron-donating nature and a larger radius, allowing it to inject more electrons into titanium dioxide (TiO2) surface. Based on our research, we have determined that these recently discovered sensitizers built upon GQD exhibit considerable potential for use in QDSCs.

Mechanical quantum analysis on the role of transition metals on the delivery of metformin anticancer drug by the boron phosphide nanotube

We scrutinized the impact of doping of X atoms (X = Fe, Co, Ni, Cu, and Zn) on the metformin (MF) drug delivery performance of a BP nanotube (BPNT) using density functional B3LYP calculations. The pristine BPNT was not ideal for the drug delivery of MF because of a weak interaction between the drug and nanotube. Doping of the Zn, Cu, Ni, Co, and Fe into the BPNT surface raised the adsorption energy of MF from −5.3 to –29.1, −28.7, −29.8, −32.1, and −26.9 kcal/mol, respectively, demonstrating that the sensitiveness of the metal-doped BPNT increased after increasing the radius atomic of metals. Ultimately, there was an increase in the adhesion performance and capacity of the MF after X (especially Co atom) doping, making the nanotube suitable for MF drug delivery. The mechanism of MF reaction with the BPNT changed from covalent bonding in the natural environment to hydrogen bonding in the cancerous cells with high acidity.

Theoretical insight into the regioselective formation of pyrazolo[1,4]-oxazepine and -oxazines

AuCl-, AuCl3-, or AuClPEt3-catalyzed formation mechanisms of pyrazolo[1,4]oxazepines and the NaH-promoted mechanism of pyrazolo[1,4]oxazines were investigated computationally. The structural properties of the reactants were studied in various solvents and with different functionals. The hybrid functionals B3LYP, M06, M06-2X, PBEPBE, and wB97X-D in density functional theory were used to determine and discuss the energetics of the compounds. The electronic properties of groups (R = H or R ≠ H) attached to the alkyne moiety played an essential role in the corresponding 7-endo-dig cyclization or 6-exo-dig cyclization in the presence of a gold catalyst. The regioselectivities of the products were investigated, and the natural bond orbitals of the reactants were determined. Furthermore, a gold-catalyzed alternative mechanism is suggested for synthesizing pyrazolo[1,4]oxazines using a terminal alkyne (R = H) moiety as substrate.

Enhanced NLO response and switching self-focussing in benzodiazepine derivative with –NO2 and -Br substitution

Optoelectronic and the cubic nonlinear optical properties of 4-(4-Bromophenyl)-2-(4-nitrophenyl)-2, 3-dihydro-1H-1, 5-benzodiazepine have been studied. Z-scan technique was used for the third-order nonlinear optical measurements namely, nonlinear absorption, nonlinear refraction, and optical power limiting behaviour employing an Nd: YAG laser of 532 nm wavelength having 5 ns Gaussian pulses. B3LYP/6–311 ++ G (d, p) level of theory was employed for structural optimization, vibrational wavenumber, frontier molecular orbitals, natural bond orbital and population analysis. The MOLVIB programme was used to perform unambiguous vibrational assignments based on potential energy distribution values acquired from normal coordinate analysis. B3LYP and CAM-B3LYP hybrid functions have been employed at the DFT level to calculate the theoretical second-order hyperpolarizability. The substitution of –NO2 and -Br in this benzodiazepine compound enhances the second-order hyperpolarizability (γ) to the order of 10−34 esu and, switching of self-defocussing to self-focussing phenomenon. The HOMO-LUMO and optical band gap analysis illustrates that polarizing nature of the molecule vary with substituents. The obtained results indicate that this compound has potential applications in optoelectronics and photonics.

Benchmarking boron cluster calculations: Establishing reliable geometrical and energetic references for Bn (n = 1-4).

Using full configuration interaction (FCI) and multi-reference configuration interaction methods (MRCI), reliable geometrical and energetic references for Bn (n = 1-4) clusters were established. The accuracy of the computed results was confirmed by comparison with available experimental data. Benchmark calculations indicated that B97D3, B97D, VSXC, HCTH407, BP86 and CCSD(T) methods provided reasonable results for structural parameters, with mean absolute error (MAEs) within 0.020 Å. Among the tested density functional theory (DFT) methods, the VSXC functional showed the best performance in predicting the relative energies of B1 B4 with a MAE of 12.8 kJ mol-1 . Besides, B1B95, B971, TPSS, B3LYP, and BLYP functionals exhibited reasonable performance with MAE values of less than 15.0 kJ mol-1 . T1 diagnostic values between 0.035 and 0.109 at the CCSD(T) level revealed strong correlations in B2 B4 clusters, highlighting the need for caution in using CCSD(T) as an energy reference for small boron clusters. The methods of CCSDT, CCSDT(Q) and CCSDT[Q], which incorporate three-electron and four-electron excitations, effectively improved the accuracy of the energy calculations.

Fully relativistic study of polyatomic closed-shell E121X3 (X = I, At, Ts) molecules: Effects of Gaunt interaction, relativistic effects and advantages of an exact-two component (X2C) hamiltonian

All electron relativistic calculations within density functional theory (DFT) with hybrid functional B3LYP were performed using 4-component Dirac-Coulomb-Gaunt, 4-component Dirac-Coulomb, Dyall’s spin-free Dirac-Coulomb, Spin-free exact two-component, exact-two component without spin–orbit screening and Levy-Leblond non-relativistic hamiltonians to investigate the relativistic effects on closed-shell E121X3 (X = I, At, Ts). The aims of this study were: a) to investigate relativistic effects, b) to verify the importance of Gaunt effects on bonding and their spectroscopic constants of these systems, and c) to verify how useful can be the use of X2C Hamiltonian. The results show that: a) the Gaunt effects are minute on bonding and in their spectroscopic constants; b) X2C/NOAMFI Hamiltonian can be useful for obtaining Re and the frequency ωe; c) there is no evidence of breaking of the periodic properties among the molecules investigated in this study.

Synthesis of N-Propargyl Pyrrolylamides and Theoretical Study of Pyrrolylimide Reduction by NaBH4

AbstractThis study is divided into two parts: experimental and theoretical. In the experimental part, N-propargyl-substituted pyrrolylamide derivatives are synthesized in five steps starting from pyrrole. The main features of this procedure are (i) the synthesis of 2- and 3-nitropyrrole, (ii) the introduction of a propargyl group on the nitrogen atom of the pyrrole, (iii) coupling of various substituents with the alkyne functionality by the Sonogashira reaction, (iv) synthesis of pyrrolylimides by a tin-catalyzed reaction with phthalic anhydride, and, finally, (v) reduction of pyrrolylimides with sodium borohydride (NaBH4) in the presence of water. The theoretical part concerns the reduction mechanism of the pyrrolylimide by NaBH4. The hybrid functional B3LYP in density functional theory is used to determine and discuss the energetics of the compounds.

Low‐Energy Driven Ring‐Opening Behavior of Benzocyclobutene Derivatives

Comprehensive SummaryIt's urgent to develop benzocyclobutene (BCB)‐based polymers with low curing temperature for temperature‐sensitive applications such as liquid crystal displays (LCDs) and flexible electronics. Herein, the effect of substituents on the ring‐opening behavior of BCB derivatives was investigated. The ring‐opening activation energy barriers (ΔGA) of BCB derivatives with one or two substituents on the four‐membered alkyl ring were systematically calculated using the B3LYP function. Both mono‐ and di‐substituted BCBs adopted the conrotatory ring‐opening process, obeying the Woodward‐Hoffmann's Rules upon heating. The mono‐/di‐substituted BCBs exhibited 8.2%—69% lower ΔGA compared with BCB, attributed to the electronic effects of the substituents. Disubstituted BCBs with both electron‐donating and electron‐withdrawing groups, e.g., 1‐NH2‐8‐NO2‐BCB, demonstrated the lowest ΔGA. In addition, BCB derivatives with amide/ester/acyloxy group modified on C1 position were synthesized as model molecules, and their ring‐opening temperature can be decreased by 20 °C compared to the unsubstituted one, also consistent with our calculation results. This work combined theoretical calculation methods with experimental results to provide valuable insights into the design and synthesis of BCB derivatives and next‐generation BCB functional packaging materials with low ring‐opening temperature.

Synthesis, theoretical properties using DFT method, and nonlinear optical properties of 4-methyl umbelliferone derivative

4-methyl umbelliferone compound is synthesized from resorcinol with ethyl acetoacetate under ultrasound irradiation as an assistant of reaction. The coumarin derivative, COM-ester compound, is synthesized from the 4-methyl umbelliferone with chloroethyl acetate also using ultrasound irradiation. The COM-ester compound is characterized via spectroscopic, FTIR and 1H NMR methods. The geometrical optimization and thermodynamic characterization of the COM-ester compound are theoretically investigated via DFT. To determine the HOMO, LUMO, Mullikan atom charges and electronic spectrum of the investigated COM-ester compound, the hybrid functional B3LYP and CAM- B3LYP procedures are applied. Nonlinear optical (NLO) properties of the COM-ester compound are studied via the diffraction patterns (DPs) and Z-scan techniques where it's nonlinear refractive index (NLRI), n2, is obtained using cw, low power laser beam. As high as 4.658 × 10−11 m2/W of n2 is obtained. The all-optical switching (AOS) of the COM-ester compound is tested using two 473 and 532 nm cw, visible laser beams, both static AOS and dynamic AOS.

Spectral Elucidations and Molecular Docking Analysis of Hydrogen Bonded Coordination Metal Complex Cadmium Nicotinate Using DFT Method

The geometry optimization, natural bond orbital analysis, and vibrational analysis of Cadmium Nicotinate (CdN) were performed using the density functional B3LYP level with a LANL2DZ basis set. Transfer of electrons from the lone pair oxygen in COO− to the antibonding orbital of the O-H bond results in the formation of hydrogen bonds, which results in the most interesting biological properties, according to natural bond orbital analysis. The red shift in wavenumber has been confirmed by intramolecular O-H…O hydrogen bonding interactions and the water group coordinated to the central metal cadmium via oxygen atoms. UV spectral analysis, on the other hand, reveals the n→π* transition due to its strong peak in absorption spectra, demonstrating its biological activity. The MEP and Fukui Functions are used to represent the molecule’s reactive region, which remains more electrophilic around the oxygen atoms. DOS spectral analysis is used to investigate the molecular orbital contributions. The Electron Localization Function (ELF) and the Local orbital locator (LOL) were used to conduct topological studies on CdN. To investigate distinct covalent and non-covalent interactions, Hirshfeld surface analysis and reduced density gradient analysis were used. Molecular docking studies were used to investigate ligand-protein interactions and ADME parameter analysis and the Lipinski rule for the CdN molecule confirmed that the compound has good drug-like properties and could be developed as an antifungal drug in the future.

Molecular design of D-π-A-π-D small molecule donor materials with narrow energy gap for organic solar cells applications.

Developing novel materials present a great challenge to improve the photovoltaic performance of organic solar cells (OSCs). In this paper, we designed a series of the donor-π bridge-acceptor-π bridge-donor (D-π-A-π-D) structure molecules. These molecules consist of diketopyrrolopyrrole (DPP) moiety as core, 9-hexyl-carbazole moiety as terminal groups, and different planar electron-rich aromatic groups as π-bridges. The density functional theory (DFT) and time-dependent DFT (TD-DFT) computations showed that the frontier molecular orbital (FMO) energy levels, energy gaps, electron-driving forces (ΔEL-L), open-circuit voltage (Voc), fill factor (FF), reorganization energy (λ), exciton binding energy (Eb), and absorption spectra of the designed molecules can be effectively adjusted by the introduction of different π-bridges. The designed molecules have narrow energy gap and strong absorption spectra, which are beneficial for improving the photoelectric conversion efficiency of organic solar cells. In addition, the designed molecules possess large ΔEL-L, large Voc, and FF values and low Eb when the typical fullerene derivatives are used as acceptors. The FMO energy levels of the designed molecules can provide match well with the typical fullerene acceptors PC61BM, bisPC61BM, and PC71BM. Our results suggest that the designed molecules are expected to be promising donor materials for OSCs. All DFT and TD-DFT calculations were carried out using the Gaussian 09 code. The computational technique chosen was the hybrid functional B3LYP and the 6-31G(d,p) basis set. The benzene and chloroform solvent effects have been considered using the polarized continuum model (PCM) at the TD-DFT level. The simulated absorption spectra of designed molecules were plotted by using the GaussSum 1.0 program.

Halogenation effects on the bridgehead position of the adamantane molecule

Halogen substitution effects on the bridgehead positioned carbon of adamantane molecule portraits many significant characteristics for the adamantane halides. As a result of the induction and electrostatic interaction caused by the substitution, large electron densities are formed around the halogens and a small positive electrostatic potential (σ-hole) is developed along the z-direction parallel to C-X bond axis. Computational study performed through EOM-CCSD method, B3LYP and WB97XD functionals of the density functional theory effectively supports this investigation in terms of molecular structure, vibrational properties, bonding behavior and electrostatic potential surfaces. Accordingly, substitution give rise to the change in the dipole moment and symmetry of the molecules. In addition, polarizabilities of the molecules along the C-X bond axis increases with respect to electron densities. HOMO-LUMO energy gap and positive σ-holes are found to decrease with the increase in the negative electron affinity. An anisotropic charge distribution developed upon substitution allows the adamantane halides to exhibit two different binding motifs like halogen and hydrogen bonding along the parallel and perpendicular directions of C-X bond. These characteristics feature of the halo adamantane finds applications in self-assembled monolayers, crystal engineering and biomedical applications.

Experimental and Theoretical Biological Probing of Schiff Bases as Esterase Inhibitors: Structural, Spectral and Molecular Insights.

The present study was designed to evaluate the in vitro and in silico potential of the Schiff bases (Z)-4-ethoxy-N-((5-nitrothiophen-2-yl)methylene)benzenamine (1) and (Z)-2,4-diiodo-6-((2-methyl-3-nitrophenylimino)methyl)phenol (2). These Schiff bases were synthesized according to a reported method using ethanol as a solvent, and each reaction was monitored on a TLC until completion of the reaction. The structures of both compounds were elucidated using spectroscopic techniques such as UV-Vis, FTIR, 1H NMR and 13C NMR. Molecular structure was determined using single-crystal XRD, which revealed that compounds 1 and 2 were monoclinic and triclinic, respectively. Hirshfeld surface analysis (HS) and 2D fingerprint plots were used to determine the intermolecular interactions along the contact contribution in the crystalline molecules. The structures of both compounds were optimized through a hybrid functional method B3LYP using the 6-31G(d,p) basis set, and various structural parameters were studied. The experimental and theoretical parameters (bond angle and bond length) of the compounds were compared with each other and are in close agreement. The in vitro esterase potential of the synthesized compounds was checked using a spectrophotometric model, while in silico molecular docking studies were performed with AutoDock against two enzymes of the esterase family. The docking studies and the in vitro assessment predicted that such molecules could be used as enzyme inhibitors against the tested enzymes: acetylcholine esterase (AChE) and butyrylcholine esterase (BChE).

Vibronic Coupling in Vitamin B12: A Combined Spectroscopic and Computational Study.

Understanding the diverse reactivities of vitamin B12 and its derivatives, collectively called cobalamins, requires detailed knowledge of their geometric and electronic structures. Electronic absorption (Abs) and resonance Raman (rR) spectroscopies have proven invaluable in this area, particularly when used in concert with computational techniques such as density functional theory (DFT). There remain, however, lingering uncertainties in the computational description of electronic excited states of cobalamins, particularly surrounding the vibronic coupling that impacts the Abs bandshapes and gives rise to rR enhancement of vibrational modes. Past computational analyses of the vibrational spectra of cobalamins have either neglected rR enhancement or calculated rR enhancement for only a small number of modes. In the present study, we used the recently developed ORCA_ASA computational tool in conjunction with the popular B3LYP and BP86 functionals to predict Abs bandshapes and rR spectra for vitamin B12. The ORCA_ASA/B3LYP-computed Abs envelope in the visible spectral region and rR spectra of vitamin B12 agree remarkably well with our experimental data, while BP86 fails to reproduce both. This finding represents a significant advance in our understanding of how these two commonly used density functionals differently model the electronic properties of cobalamins. Guided by the computed frequencies for the Co-C stretching and Co-C-N bending modes, we identified, for the first time, isotope-sensitive features in our rR spectra of 12CNCbl and 13CNCbl that can be assigned to these modes. A normal coordinate analysis of the experimentally determined Co-C stretching and Co-C-N bending frequencies indicates that the Co-C force constant for vitamin B12 is 2.67 mdyn/Å, considerably larger than the Co-C force constants reported for alkylcobalamins.