Repurposing an adenine riboswitch into a fluorogenic imaging and sensing tag.

Fluorogenic RNA aptamers are used to genetically encode fluorescent RNA and to construct RNA-based metabolite sensors. Unlike naturally occurring aptamers that efficiently fold and undergo metabolite-induced conformational changes, fluorogenic aptamers can exhibit poor folding, which limits their cellular fluorescence. To overcome this, we evolved a naturally occurring well-folded adenine riboswitch into a fluorogenic aptamer. We generated a library of roughly 1015 adenine aptamer-like RNAs in which the adenine-binding pocket was randomized for both size and sequence, and selected Squash, which binds and activates the fluorescence of green fluorescent protein-like fluorophores. Squash exhibits markedly improved in-cell folding and highly efficient metabolite-dependent folding when fused to a S-adenosylmethionine (SAM)-binding aptamer. A Squash-based ratiometric sensor achieved quantitative SAM measurements, revealed cell-to-cell heterogeneity in SAM levels and revealed metabolic origins of SAM. These studies show that the efficient folding of naturally occurring aptamers can be exploited to engineer well-folded cell-compatible fluorogenic aptamers and devices.

The fluorescent aptamer Squash extensively repurposes the adenine riboswitch fold.

Squash is an RNA aptamer that strongly activates the fluorescence of small-molecule analogs of the fluorophore of green fluorescent protein (GFP). Unlike other fluorogenic aptamers, isolated de novo from random-sequence RNA, Squash was evolved from the bacterial adenine riboswitch to leverage its optimized in vivo folding and stability. We now report the 2.7-Å resolution cocrystal structure of fluorophore-bound Squash, revealing that while the overall fold of the riboswitch is preserved, the architecture of the ligand-binding core is dramatically transformed. Unlike previously characterized aptamers that activate GFP-derived fluorophores, Squash does not harbor a G-quadruplex, sandwiching its fluorophore between a base triple and a noncanonical base quadruple in a largely apolar pocket. The expanded structural core of Squash allows it to recognize unnatural fluorophores that are larger than the simple purine ligand of the parental adenine riboswitch, and suggests that stable RNA scaffolds can tolerate larger variation than has hitherto been appreciated.

Core-ionization spectrum of liquid water.

We present state-of-the-art calculations of the core-ionization spectrum of water. Despite significant progress in procedures developed to mitigate various experimental complications and uncertainties, the experimental determination of ionization energies of solvated species involves several non-trivial steps such as assessing the effect of the surface potential, electrolytes, and finite escape depths of photoelectrons. This provides a motivation to obtain robust theoretical values of the intrinsic bulk ionization energy and the corresponding solvent-induced shift. Here we develop theoretical protocols based on coupled-cluster theory and electrostatic embedding. Our value of the intrinsic solvent-induced shift of the 1sO ionization energy of water is -1.79 eV. The computed absolute position and the width of the 1sO peak in photoelectron spectrum of water are 538.47 eV and 1.44 eV, respectively, agreeing well with the best experimental values.

Total Synthesis, Revised Structure, and Biological Evaluation of Elgonene B and Analogues.

Herein, we report the first total synthesis of elgonene B and its congeners, thus resulting in a revision of the configuration at the C-6 carbon of the originally proposed structure of elgonene B. This synthetic approach demonstrates the utility of several important reactions such as the chiral oxazaborolidinium ion-catalyzed Diels-Alder reaction, Ando's Horner-Wadsworth-Emmons olefination, and the intermolecular Nozaki-Hiyama-Kishi reaction as key steps. Additionally, the study explores the cytotoxic and antibacterial activities of elgonene B and its congeners (1-4).

Pushing the Boundary of Covalency in Lanthanoid-Tellurium Bonds: Insights from the Synthesis, Molecular and Electronic Structures of Low-Coordinate, Monomeric Europium(II) and Ytterbium(II) Tellurolates.

Owing to the strict hard/soft dichotomy between the lanthanoids and tellurium atoms, and the strong affinity of lanthanoid ions for high coordination numbers, low-coordinate, monomeric lanthanoid tellurolate complexes have remained elusive as compared to the lanthanoid complexes with lighter group 16 elements (O, S, and Se). This makes the development of suitable ligand systems for low-coordinate, monomeric lanthanoid tellurolate complexes an appealing endeavor. In a first report, a series of low-coordinate, monomeric lanthanoid (Yb, Eu) tellurolate complexes were synthesized by utilizing hybrid organotellurolate ligands containing N-donor pendant arms. The reaction of bis[2-((dimethylamino)methyl)phenyl] ditelluride, 1 and 8,8'diquinolinyl ditelluride, 2 with Ln0 metals (Ln=Eu, Yb) resulted in the formation of monomeric complexes [LnII (TeR)2 (Solv)2 ] [R=C6 H4 -2-CH2 NMe2 ] [3: Ln=Eu, Solv=tetrahydrofuran; 4: Ln=Eu, Solv=acetonitrile; 5: Ln=Yb, Solv=tetrahydrofuran; 6: Ln=Yb, Solv=pyridine] and [EuII (TeNC9 H6 )2 (Solv)n ] (7: Solv=tetrahydrofuran, n=3; 8: Solv=1,2-dimethoxyethane, n=2), respectively. Complexes 3-4 and 7-8 represent the first sets of examples of monomeric europium tellurolate complexes. The molecular structures of complexes 3-8 are validated by single-crystal X-ray diffraction studies. The electronic structures of these complexes were investigated using Density Functional Theory (DFT) calculations, which revealed appreciable covalency between the tellurolate ligands and lanthanoids.

Long Non-coding RNAs, Lnc(ing) RNA Metabolism to Cancer Biology.

The eukaryotic genome is represented by a vast proportion of non-coding regions, which in recent years have been attributed to have important functional roles in gene regulation through a myriad of processes, ranging from proper localization, correct folding and, most importantly, spatial and temporally regulated expression of genes. One of the major contributing factors in these processes is ribonucleic acid (RNA) metabolism, which comprises the RNA-nucleoprotein (RNP) complexes that interact with and instruct the genome to function. Long non-coding RNAs are an integral component of several RNPs, and herein we provide an overview of the understanding of the long non-coding RNAs, their characteristics, their function and their balancing act as dual modulators in cancer manifestation and progression.

Phytoconstituents from Urtica dioica (stinging nettle) of Sikkim Himalaya and their molecular docking interactions revealed their nutraceutical potential as α-amylase and α-glucosidase inhibitors.

In this study, antioxidative methanolic leaf extract (MeOH-SIS) of Urtica dioica was characterized for anti-diabetic activity. The extract was purified on a column to yield seven homogenous fractions (F1-F7) which were further determined for DPPH radical scavenging activity. MeOH-SIS and the fraction F1 (selected based on % yield and activity) were evaluated for their in vitro α-amylase and α-glucosidase inhibitory activity. The results showed inhibition of both enzymes in a dose dependent manner and F1 exhibited relatively higher inhibition than its mother extract MeOH-SIS. GC-MS analyses of both the extracts identified 24 major compounds among which 10 were previously described as bioactive compounds. Among all, 5 compounds demonstrated to have quality pharmacokinetics profiles and were examined for possible binding affinity against the active sites of α-amylase and α-glucosidase using molecular docking. The binding interaction of 2R-acetoxymethyl-1,3,3-trimethyl-4 T-(3-methyl-2-buten-1-yl)-1 T-cyclohexanol within the active sites of the target receptors was found to be significant among others, and can be developed as a potential inhibitor of α-amylase and α-glucosidase. The leaf extract can be utilized to develop food additive for the control and management of oxidative stress induced diabetes.

Whole genome sequencing and comparative genomic analyses of Pseudomonas aeruginosa strain isolated from arable soil reveal novel insights into heavy metal resistance and codon biology.

Elevated concentration of non-essential persistent heavy metals and metalloids in the soil is detrimental to essential soil microbes and plants, resulting in diminished diversity and biomass. Thus, isolation, screening, and whole genomic analysis of potent strains of bacteria from arable lands with inherent capabilities of heavy metal resistance and plant growth promotion hold the key for bio remedial applications. This study is an attempt to do the same. In this study, a potent strain of Pseudomonas aeruginosa was isolated from paddy fields, followed by metabolic profiling using FTIR, metal uptake analysis employing ICP-MS, whole genome sequencing and comparative codon usage analysis. ICP-MS study provided insights into a high degree of Cd uptake during the exponential phase of growth under cumulative metal stress to Cd, Zn and Co, which was further corroborated by the detection of cadA gene along with czcCBA operon in the genome upon performing whole-genome sequencing. This potent strain of Pseudomonas aeruginosa also harboured genes, such as copA, chrA, znuA, mgtE, corA, and others conferring resistance against different heavy metals, such as Cd, Zn, Co, Cu, Cr, etc. A comparative codon usage bias analysis at the genomic and genic level, whereby several heavy metal resistant genes were considered in the backdrop of two housekeeping genes among 40 Pseudomonas spp. indicated the presence of a relatively strong codon usage bias in the studied strain. With this work, an effort was made to explore heavy metal-resistant bacteria (isolated from arable soil) and whole genome sequence analysis to get insight into metal resistance for future bio remedial applications.

Analysis of the Magnetic Coupling in a Mn(II)-U(V)-Mn(II) Single Molecule Magnet.

[{Mn(TPA)I}{UO2(Mesaldien)}{Mn(TPA)I}]I formula (here TPA=tris(2-pyridylmethyl)amine and Mesaldien=N,N'-(2-aminomethyl)diethylenebis(salicylidene imine)) reported by Mazzanti and coworkers (Chatelain et al. Angew. Chem. Int. Ed. 2014, 53, 13434) is so far the best Single Molecule Magnet (SMM) in the {3d-5f} class of molecules exhibiting barrier height of magnetization reversal as high as 81.0 K. In this work, we have employed a combination of ab initio CAS and DFT methods to fully characterize this compound and to extract the relevant spin Hamiltonian parameters. We show that the signs of the magnetic coupling and of the g-factors of the monomers are interconnected. The central magnetic unit [UV O2 ]+ is described by a Kramers Doublet (KD) with negative g-factors, due to a large orbital contribution. The magnetic coupling for the {Mn(II)-U(V)} pair is modeled by an anisotropic exchange Hamiltonian: all components are ferromagnetic in terms of spin moments, the parallel component JZ twice larger as the perpendicular one J⊥ . The spin density distribution suggests that spin polarization on the U(V) center favors the ferromagnetic coupling. Further, the JZ /J⊥ ratio, which is related to the barrier height, was found to correlate to the corresponding spin contribution of the g-factors of the U(V) center. This correlation established for the first time offers a direct way to estimate this important ratio from the corresponding gS -values, which can be obtained using traditional ab initio packages and hence has a wider application to other {3d-5f} magnets. It is finally shown that the magnetization barrier height is tuned by the splitting of the [UV O2 ]+ 5 f orbitals.

Deciphering the Role of Anions and Secondary Coordination Sphere in Tuning Anisotropy in Dy(III) Air-Stable D5h SIMs.

Precise control of the crystal field and symmetry around the paramagnetic spin centre has recently facilitated the engineering of high-temperature single-ion magnets (SIMs), the smallest possible units for future spin-based devices. In the present work, we report a series of air-stable seven coordinate Dy(III) SIMs {[L2 Dy(H2 O)5 ][X]3 ⋅L2 ⋅n(H2 O), n = 0, X = Cl (1), n=1, X = Br (2), I (3)} possessing pseudo-D5h symmetry or pentagonal bipyramidal coordination geometry with high anisotropy energy barrier (Ueff ) and blocking temperature (TB ). While the strong axial coordination from the sterically encumbered phosphonamide, t BuPO(NHi Pr)2 (L), increases the overall anisotropy of the system, the presence of high symmetry significantly quenches quantum tunnelling of magnetization, which is the prominent deactivating factor encountered in SIMs. The energy barrier (Ueff ) and the blocking temperature (TB ) decrease in the order 3>2>1 with the change of anions from larger iodide to smaller strongly hydrogen-bonded chloride in the secondary coordination sphere, albeit the local coordination geometry and the symmetry around the Dy(III) display only slight deviations. Ab initio CASSCF/RASSI-SO/SINGLE_ANISO calculations provide deeper insights into the dynamics of magnetic relaxation in addition to the role of the secondary coordination sphere in modulating the anisotropy of the D5h systems, using diverse models. Thus, in addition to the importance of the crystal field and the symmetry to obtain high-temperature SIMs, this study also probes the significance of the secondary coordination sphere that can be tailored to accomplish novel SIMs.

Deciphering the Role of Symmetry and Ligand Field in Designing Three-Coordinate Uranium and Plutonium Single-Molecule Magnets.

Actinide single-molecule magnets (SMMs) have gained paramount interest in molecular magnetism as they offer a larger barrier height of magnetization (Ueff) reversal compared to the lanthanide analogue, thanks to their greater metal-ligand covalency. However, the reported actinide SMMs to date yield a relatively smaller Ueff as there is no established design principle to enhance Ueff values. To address this issue, we have employed ab initio CASSCF/CASPT2/NEVPT2 calculations to study a series of three-coordinate U3+ and Pu3+ SMMs. To begin with, we have studied two experimentally characterized U3+ ion-field-induced SMMs, namely, planar [U{N(SiMe2tBu)2}3] (1) and pyramidal [U{N(SiMe3)2}3] (2) complexes reported earlier. Both the complexes were found to stabilize mJ = |±1/2⟩ as the ground state with a very strong quantum tunneling of magnetization (QTM), rendering them unsuitable for SMMs. Our calculations reveal that in the pyramidal geometry (such as in 2), the energy of the 5f26d1 state is lowered compared to the planar geometry (as in 1), resulting in a slightly better SMM characteristic in the former. To unravel the effect of symmetry in magnetic properties, ab initio calculations were performed on two reported T-shaped complexes [U(NSiiPr2)2(I)] (3) and [U(NHAriPr6)2I] (4, AriPr6 = 2,6-(2,4,6-iPr3C6H2)2C6H3). Quite interestingly, mJ = |±9/2⟩ is found to be the ground state for both the complexes with a blocking barrier exceeding 900 cm-1. Furthermore, to decipher the effect of the transuranic element in magnetic anisotropy, ab initio calculations were extended to the Pu analogue of 2, [Pu{N(SiMe3)2}3] (5), which yields a record-breaking blocking barrier of ∼1933 cm-1. Among the three-coordinate geometries studied, the pyramidal geometry was found to offer substantial magnetic anisotropy for Pu3+ ions, while a T-shaped geometry is best suited for U3+ ions. While the chosen theoretical protocols' overestimation of barrier height cannot be avoided, these values are still several orders of magnitude larger than the Ueff values reported for any actinide SMMs and unveil a design principle for superior three-coordinate actinide-based SMMs.

Imaging Intracellular S-Adenosyl Methionine Dynamics in Live Mammalian Cells with a Genetically Encoded Red Fluorescent RNA-Based Sensor.

To understand the role of intracellular metabolites in cellular processes, it is important to measure the dynamics and fluxes of small molecules in living cells. Although conventional metabolite sensors composed of fluorescent proteins have been made to detect some metabolites, an emerging approach is to use genetically encoded sensors composed of RNA. Because of the ability to rapidly generate metabolite-binding RNA aptamers, RNA-based sensors have the potential to be designed more readily than protein-based sensors. Numerous strategies have been developed to convert the green-fluorescent Spinach or Broccoli fluorogenic RNA aptamers into metabolite-regulated sensors. Nevertheless, red fluorescence is particularly desirable because of the low level of red background fluorescence in cells. However, the red fluorescent variant of the Broccoli aptamer, Red Broccoli, does not exhibit red fluorescence in cells when imaged with its cognate fluorophore. It is not known why Red Broccoli is fluorescent in vitro but not in live mammalian cells. Here, we develop a new fluorophore, OBI (3,5-difluoro-4-hydroxybenzylidene-imidazolinone-2-oxime-1-benzoimidazole), which binds Red Broccoli with high affinity and makes Red Broccoli resistant to thermal unfolding. We show that OBI enables Red Broccoli to be readily detected in live mammalian cells. Furthermore, we show that Red Broccoli can be fused to a S-adenosyl methionine (SAM)-binding aptamer to generate a red fluorescent RNA-based sensor that enables imaging of SAM in live mammalian cells. These results reveal a red fluorescent fluorogenic aptamer that functions in mammalian cells and that can be readily developed into red fluorescent RNA-based sensors.

Role of Coordination Number and Geometry in Controlling the Magnetic Anisotropy in FeII , CoII , and NiII Single-Ion Magnets.

Since the last decade, the focus in the area of single-molecule magnets (SMMs) has been shifting constructively towards the development of single-ion magnets (SIMs) based on transition metals and lanthanides. Although ground-breaking results have been witnessed for DyIII -based SIMs, significant results have also been obtained for some mononuclear transition metal SIMs. Among others, studies based on CoII ion are very prominent as they often exhibit high magnetic anisotropy or zero-field splitting parameters and offer a large barrier height for magnetisation reversal. Although CoII possibly holds the record for having the largest number of zero-field SIMs known for any transition metal ion, controlling the magnetic anisotropy in these systems are is still a challenge. In addition to the modern spectroscopic techniques, theoretical studies, especially ab initio CASSCF/NEVPT2 approaches, have been used to uncover the electronic structure of various CoII SIMs. In this article, with some selected examples, the aim is to showcase how varying the coordination number from two to eight, and the geometry around the CoII centre alters the magnetic anisotropy. This offers some design principles for the experimentalists to target new generation SIMs based on the CoII ion. Additionally, some important FeII /FeIII and NiII complexes exhibiting large magnetic anisotropy and SIM properties are also discussed.

Pentagonal Bipyramidal Ln(III) Complexes Containing an Axial Phosphine Oxide Ligand: Field-induced Single-ion Magnetism Behavior of the Dy(III) Analogues.

A series of neutral homologous complexes [(L)Ln(Cy3PO)Cl] {where Ln = Gd (1), Tb (2), Dy (3), and Er (5)} and [(L)Dy(Ph3PO)Cl] (4) [H2L = 2,6-diacetylpyridine bis-benzoylhydrazone] were isolated. In these complexes, the central lanthanide ion possesses a pentagonal bipyramidal geometry with an overall pseudo D5h symmetry. The coordination environment around the lanthanide ion comprises of three nitrogen and two oxygen donors in an equatorial plane. The axial positions are taken up by a phosphine oxide (O donor) and a chloride ion. Among these compounds, the Dy(III) (3 and 4) analogues were found to be field-induced single-ion magnets.

High-Pressure Crystallographic and Magnetic Studies of Pseudo-D5h Symmetric Dy(III) and Ho(III) Single-Molecule Magnets.

Single-ion magnets based on lanthanide ions in pseudo-D5h symmetry have gained much attention in recent years as they are reported to possess a large blocking temperature and a large barrier for magnetization reversal. Magneto-structural correlations reveal that the axial O-Ln-O angle is an important parameter to control the barrier, and while it can be fine-tuned by chemical modification, an alternative would be to utilize hydrostatic pressure. Herein, we report the crystal structures and static magnetic properties of two air-stable isostructural lanthanide SIMs under applied pressures. The complexes exhibit pseudo-D5h symmetry around the Ln(III)-ion (Ln = Dy or Ho), which coordinates to five equatorial water molecules and two large neutral phosphonic diamide ligands along the axial direction. High-pressure single-crystal X-ray diffraction experiments revealed two phase-transitions and an increasing deviation from D5h-symmetry between ambient pressure and 3.6 GPa. High-pressure direct-current magnetic measurements of the Dy(III) compound showed large steps in the hysteresis loops near zero field, indicative of quantum tunneling of magnetization (QTM). These steps grow in size with increasing pressure, suggesting that QTM becomes progressively more active, which correlates well with the pressure-induced increased overall deviation from pseudo-D5h symmetry and decreasing axial O-Dy-O angle. A strong temperature dependence of the step size is seen at 0.3 GPa, which shows that the SMM character persists even at this pressure. To understand the origin of significant variation in the tunneling probability upon pressure, we performed a range of ab initio calculations based on the CASSCF/RASSI-SO/SINGLE_ANISO method on both Dy and Ho complexes. From the energies and magnetic anisotropy of the mJ sublevels, we find a complex variation of the energy barrier with pressure, and using a constructed geometrical parameter, R, taking into account changes in both bond angles and distances, we link the magnetic properties to the first coordination sphere of the molecules.

Insight into D6h Symmetry: Targeting Strong Axiality in Stable Dysprosium(III) Hexagonal Bipyramidal Single-Ion Magnets.

Following a novel synthetic strategy where the strong uniaxial ligand field generated by the Ph3 SiO- (Ph3 SiO- =anion of triphenylsilanol) and the 2,4-di-t Bu-PhO- (2,4-di-t Bu-PhO- =anion of 2,4-di-tertbutylphenol) ligands combined with the weak equatorial field of the ligand LN6 , leads to [DyIII (LN6 )(2,4-di-t Bu-PhO)2 ](PF6 ) (1), [DyIII (LN6 )(Ph3 SiO)2 ](PF6 ) (2) and [DyIII (LN6 )(Ph3 SiO)2 ](BPh4 ) (3) hexagonal bipyramidal dysprosium(III) single-molecule magnets (SMMs) with high anisotropy barriers of Ueff =973 K for 1, Ueff =1080 K for 2 and Ueff =1124 K for 3 under zero applied dc field. Ab initio calculations predict that the dominant magnetization reversal barrier of these complexes expands up to the 3rd Kramers doublet, thus revealing for the first time the exceptional uniaxial magnetic anisotropy that even the six equatorial donor atoms fail to negate, opening up the possibility to other higher-order symmetry SMMs.

An [FeIII 34 ] Molecular Metal Oxide.

The dissolution of anhydrous iron bromide in a mixture of pyridine and acetonitrile, in the presence of an organic amine, results in the formation of an [Fe34 ] metal oxide molecule, structurally characterised by alternate layers of tetrahedral and octahedral FeIII ions connected by oxide and hydroxide ions. The outer shell of the complex is capped by a combination of pyridine molecules and bromide ions. Magnetic data, measured at temperatures as low as 0.4 K and fields up to 35 T, reveal competing antiferromagnetic exchange interactions; DFT calculations showing that the magnitudes of the coupling constants are highly dependent on both the Fe-O-Fe angles and Fe-O distances. The simplicity of the synthetic methodology, and the structural similarity between [Fe34 ], bulk iron oxides, previous FeIII -oxo cages, and polyoxometalates (POMs), hints that much larger molecular FeIII oxides can be made.

Accessibility of Densely Localized DNA on Soft Polymer Nanoparticles.

The dense localization of DNA on soluble nanoparticles can lead to effects distinct from equivalent amounts of the DNA in solution. However, the specific effect may depend on the nature of the assembly and the nanoparticle core. Here we examine the accessibility of densely packed DNA duplexes that extend from a bottle-brush polymer core. We find that unlike spherical nucleic acids, the DNA duplex bristles on the bottle-brush polymer remain accessible to sequence-specific cleavage by endonucleases. In addition, the hybridized strand of the duplex can be displaced through a toehold-mediated strand exchange even at the polymer interface. These results demonstrate that the DNA on bottle-brush polymer remains sufficiently flexible to allow enzymatic degradation or DNA hybridization.

Magneto-Structural Properties and Theoretical Studies of a Family of Simple Heterodinuclear Phenoxide/Alkoxide Bridged MnIIILnIII Complexes: On the Nature of the Magnetic Exchange and Magnetic Anisotropy.

A family of MnIIILnIII strictly dinuclear complexes of general formula [MnIII(µ-L)(µ-OMe)(NO3)LnIII(NO3)2(MeOH)] (LnIII = Gd, Dy, Er, Ho) has been assembled in a one pot synthesis from a polydentate, multipocket aminobis(phenol)ligand [6,6'-{(2-(1-morpholyl)ethylazanediyl)bis(methylene)}bis(2-methoxy-4-methylphenol)], Mn(NO3)2·4H2O, Ln(NO3)3· nH2O, and NEt3 in MeOH. These compounds represent the first examples of fully structurally and magnetically characterized dinuclear MnIIILnIII complexes. Single X-ray diffraction studies reveal that all complexes are isostructural, consisting of neutral dinuclear molecules where the MnIII and LnIII metal ions, which exhibit distorted octahedral MnN2O4 and distorted LnO9 coordination spheres, are linked by phenoxide/methoxide double bridging groups. Static magnetic studies show that the MnIIIGdIII derivative exhibits a weak antiferromagnetic interaction between the metal ions, with a negative axial zero-field splitting D parameter. The MnIIIGdIII complex shows a notable magnetocaloric effect with magnetic entropy change at 5 T and 3 K of -Δ Sm = 16.8 J kg-1 K-1. Theoretical studies were performed to support the sign and magnitude of the magnetic anisotropy of the MnIII ion ( ab initio), to predict the value and nature of JMnGd, to disclose the mechanism of magnetic coupling, and to establish magneto-structural correlations (DFT calculations). The results of these calculations are corroborated by quantum theory of atoms in molecule analysis (QTAIM). Finally, MnIII-DyIII and MnIII-ErIII complexes show field-induced slow relaxation of the magnetization but without reaching a maximum above 2 K in the out-of-phase ac susceptibility. Ab initio calculations were also performed on MnIII-DyIII/HoIII systems to unravel the origin behind the weak SMM characteristics of the molecules possessing two strongly anisotropic ions. The mechanism of magnetic relaxation was developed, revealing a large QTM/tunnel splitting at the single-ion level. Furthermore, the anisotropy axes of the MnIII and LnIII ions were calculated to be noncollinear, leading to reduction of the overall anisotropy in the molecules. Hence, the herein reported complexes demonstrate that a combination of two anisotropic metal ions does not guarantee SMM behavior.