Most biological functions and many chemical processes are driven by chiral nanoscale molecular machines in solution, whose structures evolve on multiple time and length scales: from the ultrafast rotations of photo-driven synthetic molecular motors to the global conformational changes of proteins on the microsecond time scale. Yet capturing the associated conformational transitions in real-time continues to be a formidable experimental challenge, as prominent established methods come with their own limitations: solution nuclear magnetic resonance is limited to millisecond real-time resolution, whilst solution X-Ray scattering requires large-scale X-Ray facilities. A promising laboratory-based alternative is circular dichroism (CD), the absorption difference of left- and right-handed circularly polarized light, which is sensitive to the chiral geometrical arrangement of light-absorbing chemical groups within a molecular system. Steady-state CD is already a well-established tool in the far and middle ultraviolet (UV) < 300 nm, where equilibrium structures of proteins, DNA and functional chiral organic complexes are routinely characterized. However, pushing this technique into the time-domain has remained a challenge for over three decades, with only few isolated reports with sub-nanosecond resolution [1]. In this talk, I will present a technological breakthrough with the first time-resolved CD (TRCD) spectrometer that combines highly sensitive broadband UV-detection (250-370 nm) with pulsed laser sources and sub-picosecond time-resolution [2]. With this instrument, it is now possible to extract broadband CD spectra of photo-excited molecular states and follow their transient chirality changes with femtosecond resolution. This is opening a new avenue for capturing solution-phase structural dynamics in chemical and biological systems that I will illustrate with two examples: the coupling of electronic and structural dynamics in a chiral supramolecular metal-complex [3], and the application of a site-specific CD-label to track conformational changes of the peptide backbone [4]. On this basis I will present future developments that will establish TRCD as a complementary method for research in protein dynamics and chiral photochemistry, where the chirality of excited electronic states is the key design feature of chiral organic light-emitting diode materials and unidirectional molecular motors, for example. [mehr]